Streptococcuspyogenes (Group A)
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Diagnosis Treatment and Prevention
Gram + cocci
β-hemolytic
extracellular
——————
- human reservoir
(colonize throat and skin)
- transmission by aerosolized fomites & direct contact
——————
1) M protein: complexes with LTA to bind fibronectin and adhere; complexes with factor H to coat bacteria (molecular mimicry) and avoid alternate complement pathway and phagocytosis; induces autoantibodies with react with cardiac tissue
2) lipoteichoic acid (LTA): attaches to fibronectin on oropharyngeal cells; promotes inflammation
3) hyaluronic acid capsule: inhibits phagocytosis; molecular mimicry (identical to human ground substance)
4) C5a peptidase: cleaves C5a
5A) Streptolysin O (SLO): β-hemolysis
5B) Streptolysin S (SLS): β-hemolysis
6)Streptokinase (SKA): clot dissolution
7) Streptodornase (DNAse B): digests DNA
8) Hyaluronidase: digests hyaluronic acid in capsule and tissue
9) Erythrogenic toxin: superantigen that diffusely activates T cells and damages small blood vessels; associated with scarlet fever & TSS
10) protein G: binds Ig Fc portion
--------------------- mucosal infections - local spread from pharyngeal colonization pyogenic infections - local spread or bacteremia - multiple target organs toxigenic infections - local infection acts as a site for toxin secretion to host (e.g. erythrogenic toxin) immunologic - rheumatic fever caused by GAS proteins which target host organs - post-streptococcal glomerulonephritis caused by deposition of antibody-antigen complexes ---------------------- mucosal infections - pharyngitis pyogenic infections - necrotizing fasciitis toxigenic infections - scarlet fever - toxic shock syndrome immunologic - rheumatic fever -post-streptococcal glomerulonephritis
- can be classified by M protein type
- all antibacterial medications EXCEPT
1) Ceftazidime
2) Monobactams
3) Tetracyclines
4) TMP/SMX
5) Rifampin (not as monotherapy)
6) Metronidazole
7) Polymyxins
Mycobacterium tuberculosis
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Diagnosis Treatment and Prevention
atypical rod with waxy coating slow-growing primarily intracellular aerobic ----------------------- - inhalation of aerosolized bacteria - only people with active disease are contagious
- Kat G: catylase/peroxidase that prevents death from ROS
- mycolic acid: long chain fatty acid that is a major component of cell walls; required for cell viability
- lipoarabinomannan (LAM): mycobacterial version of LPS; signals host molecules
- other lipids: survival, immunomodulatory
- persistence genes
- macrophage survival genes
- ESX loci (e.g. ESAT-6/CFP-10): secretion systems; also immunostimulatory
- inhibit phagosome-lysosome fusion
- resistant to lysosomal enzymes due to cell wall
- down-regulate MHCII presentation to avoid detection by CD4 cells
1) enter alveolar macrophages via phagocytosis (complement receptor and mannose receptor can enhance this process)
2) inflammatory signals from infected cells
3) recruitment of monocytes (which become macrophages) and lymphocytes to lungs
4) caseous granuloma formation (necrotic center)
5) active TB: bacteria escape and form more granulomas
6) latent TB: bacteria is contained by granuloma; becomes fibrotic and may become calcified
7) reactivation: bacteria escape TB due to age or immunosuppression
8) can spread to other organs through blood
- host immune response contributes to pathology
pulmonary TB
- lung destruction
- pulmonary hemorrhage and hemoptysis
- fever
- wasting
- sepsis
extrapulmonary TB
- spread through blood to other organs after pulmonary infection
- Pott’s disease: disease of the spine; usually occurs in children
- meningitis, usually in children
- TB of GI tract
- TB of lymph nodes
miliary TB
- spreads throughout lungs or throughout body
- typically occurs in children or immunocompromised people
50% fatality if untreated
primary TB = active TB within 1-2 years of initial infection
- latent TB = infection without clinical disease
- reactivation TB = reactivation of latent infection that results in active TB; can occur in the lungs or elsewhere
- PPD test: antigen mixture is injected under skin of forearm; T cell-mediated delayed type hypersensitivity reaction occurs if the person is infected
- IGRA (IFN-γ release assay): measures IFN-γ production by ELISA following stimulation of blood with ESAT-6 + CFP-10; used to distinguish Mtb infection from BCG vaccination or non-tuberculous mycobacteria sensitization
- CXR: lesion or cavity indicates infection and disease
- acid-fast stain of sputum
- culture (takes a long time)
- PCR-based detection that also indicates drug resistance
----------------------- use all 4 of these for the first 2 months: - Rifampin - Isoniazid - Ethambutol - Pyrazinamide use both of these for the next 4 months: - Rifampin - Isoniazid add this if the bacteria is resistant to the drugs listed above: - Moxifloxacin airborne precautions
Mycobacterium leprae
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Diagnosis Treatment and Prevention
atypical rod with waxy coating obligate intracellular cannot culture ----------------------- - respiratory - can infect armadillos
- waxy coating provides resistance to desiccation and phagocytosis
- capsule containing phenolic glycolipid (PGL-1)
- lives in macrophages & Schwann cells
lepromatous leprosy - type 2 immune response
- CD8 >CD4
- IL-4, IL-10
- antibodies
- nerve damage is the result of bacteria replicating in Schwann cells
- erythema nodosum leprosum most likely immune complex-mediated
tuberculoid leprosy - CD4 > CD8
- IFN-γ, IL-2
- macrophage activation
- cell-mediated response
- ## nerve damage is the result of inflammation in tuberculoid leprosy
- lesions are flat, depigmented, and anesthetic lepromatous leprosy - skin lesions, sensory deficits, enlarged peripheral nerves, dermal edema, disfigurement of nose and face tuberculoid leprosy - skin lesions & peripheral nerve damage - erythema nodosum leprosum: painful nodules and neuritis; occurs most often after antibiotic treatment ----------------------- - diagnose by skin biopsy stained with hematoxylin and eosin and acid-fast stain lepromatous leprosy - high bacterial load - few lymphocytes - foamy macrophages - lack of granulomas - negative DTH (response to leprosy antigen lepromin) due to anergy tuberculoid leprosy - low bacterial load - numerous lymphocytes in lesions - granulomas - positive DTH test ----------------------- - Rifampin - Dapsone
Mycobacterium avium complex
(MAC)
(includes M. avium and M. intracellulare)
Morphology
Transmission and Reservoir
Virulence Factors
Diseases
Diagnosis
Treatment and Prevention
atypical rod with waxy coating
- environmental
- waxy coating provides resistance to desiccation and phagocytosis
-AIDS patients
- fever
- wasting
- may be disseminated to blood and bone marrow
- pulmonary disease (rare)
Children
- cervical lymphadenitis
———————–
- acid-fast stain
———————–
- macrolides
Mycobacterium marinum
Morphology
Transmission and Reservoir
Virulence Factors
Diseases
Diagnosis
atypical rod with waxy coating
- marine organism - ---------------------- - waxy coating provides resistance to desiccation and phagocytosis - ----------------------
- swimmer’s granuloma / fish tank
granuloma
———————– - ## acid-fast stain
Mycobacterium kansaii
Morphology
Transmission and Reservoir
Virulence Factors
Diagnosis
atypical rod with waxy coating
- environmental
- waxy coating provides resistance to desiccation and phagocytosis
acid-fast stain
———————–
Mycobacterium ulcerans
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Diagnosis
atypical rod with waxy coating
- environmental
- endemic in parts of Africa and Australia
- transmitted by water bugs?
- waxy coating provides resistance to desiccation and phagocytosis
- extracellular, unlike others
- toxin necrotizes skin
- Buruli ulcer
- acid-fast stain
Mycobacterium fortuitum
Morphology
Transmission and Reservoir
Virulence Factors
Diagnosis
atypical rod with waxy coating
- environmental
- usually causes disease in immunocompromised people
- waxy coating provides resistance to desiccation and phagocytosis
- acid-fast stain
Rickettsia rickettsii
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Diagnosis Treatment and Prevention
atypical; Gram- structure; pleomorphic
obligate intracellular
- ability to direct actin reorganization resulting in the formation of filopodia that enhance spread between cells
- ## phospholipases, proteases, and membrane peroxidation result in host cell damage1) enters through tick bite
2) spread via lymph and blood
2) grows inside vascular endothelial cells and causes lysis and rash - ## escapes phagosome to live in cytoplasmRocky Mountain spotted fever
1) spotted rash 2-4 days after onset (not always seen)
2) fever, malaise, headache, myalgias, vomiting, abdominal pain, diarrhea, conjunctivitis, mental confusion, meningitis, respiratory difficulties, renal dysfunction, myocarditis
3) 25% fatality if untreated; 4% fatality if treated
———————– - ## can be non-specifically detected by Weil-Felix test (not currently used clinically)
- Doxycycline
Chlamydia trachomatis
Morphology
Transmission and Reservoir
Pathogenesis
Diseases
atypical; Gram- structure w/o peptidoglycan; pleomorphic
elementary & reticulate bodies
obligate intracellular
STD, perinatal transmission
———————–
1) grows within epithelial cells of ocular & genital mucosa
2) results in chronic inflammatory response & scarring
3) adaptive immune response cannot prevent re-infection
4) L serovars (which cause LGV) infect macrophages and lymph nodes
———————–
- often asymptomatic
- men: Urethritis → epididymitis, arthritis, Reiter’s syndrome (arthritis + Urethritis + conjunctivitis)
- women: Urethritis, cervicitis → endometritis, salpingitis, PID → infertility, ectopic pregnancy
- babies: conjunctivitis, pneumonia
- LGV: primary lesion → fever, headache, myalgias → lymph node inflammation → lymph node rupture, elephantiasis, proctitis, rectal damage
Chlamydia pneumoniae
Morphology
Diseases
Treatment and Prevention
atypical; Gram- structure w/o peptidoglycan; pleomorphic elementary & reticulate bodies obligate intracellular energy parasite ----------------------- community-acquired pneumonia ----------------------- - tetracyclines - fluoroquinolones - macrolides
Chlamydia psittaci
Morphology
Transmission and Reservoir
Diseases
atypical; Gram- structure w/o peptidoglycan; pleomorphic
elementary & reticulate bodies
obligate intracellular
energy parasite ----------------------- birds ----------------------- psittacosis (pneumonia)
Treponema pallidum
(Spirochete)
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Diagnosis Treatment and Prevention
atypical; Gram - structure; spiral-shaped; endoflagellum
- STD
- ## can cross the placentano LPS on outer membrane,
GAGs in outer sheath (molecular mimicry)
———————–
1) infection through skin abrasions & mucous membranes
2) spreads throughout blood
3) colonizes spleen and lymph nodes in latent phase
4) reactivates
———————– - primary syphilis: chancre
- secondary syphilis: rash (entire body including palms and soles of feet), lymphadenopathy, condyloma lata
- tertiary syphilis: gummas, neurosyphilis, heart problems
- congenital syphilis: stillbirth or premature; enlarged liver & spleen, skeletal involvement, pneumonia, skin lesions
- ## congenital syphilis after 2 years: bone, tooth, & skin malformations, pathologic changes in CNS
- visualize by dark field microscopy
- ## serologic tests (treponemal & non-treponemal)
- penicillin
- aminopenicillin
Borrelia burgdorferi (Spirochete)
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Diagnosis Treatment and Prevention
- reservoir: rodents (white-footed mouse)
- transmission: deer tick bite (nymph or adult stage); transmission requires at least 36 hours
- ## found in northeast, northern midwest, and northwest (Washington)Osps: surface lipoproteins that are differentially expressed in
tick and human hosts; important for tissue attachment and for activation of growth; attaches to proteoglycans receptors at site where it grows
———————–
1) bacteria is injected during tick bite
2) local replication in skin (days)
3) widespread dissemination to other organs (days-weeks)
local inflammatory reaction (lymphocytes & plasma cells)
———————–
Lyme disease - early stage (2-30 days): erythema migrans rash (not always present), malaise, fatigue, headache, fever, chills, myalgias
- early disseminated (2 weeks - 6 months): neurological, ocular, and/or cardiac symptoms
- late (2 months - 7 years): oligoarthritis, chronic dermatologic syndromes, neurologic symptoms
- ## post-treatment Lyme disease syndromes: similar to chronic fatigue, fibromyalgia; likely autoimmune, not chronic infection
- visualize by dark field microscopy
- ## diagnose with ELISA and Western blot
- Doxycycline
- Amoxicillin
- Ceftriaxone
Leptospira
(Spirochete)
Morphology
Diseases
atypical; Gram - structure; spiral-shaped
leptospirosis
Mycoplasma pneumoniae
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases
Treatment and Prevention
atypical; no cell wall; sterols in plasma membrane
- human reservoir
- inhalation of respiratory droplets
- adhesins
- CARDS toxin: ADP-ribosylating and vacuolating cytotoxin
- peroxides damage epithelium
- 1) inhalation
2) nasopharyngeal colonization
3) aspiration
4) bronchopneumonia (does not enter alveoli)
5) inflammatory response damages respiratory epithelium - often asymptomatic
- persistent cough (“walking pneumonia”)
- erythema multiforme rash
- anemia
- tetracyclines
- fluoroquinolones
- macrolides
Candida albicans
Morphology
Transmission and Reservoir
Diseases
Treatment and Prevention
yeast ----------------------- - mouth, skin, GI tract, vagina - occurs when there is a breach in the host immune defense - usually endogenous infection - can be passed between people in some instances ----------------------- - oral thrush - esophagitis - vaginitis - bloodstream infection - abscesses - catheter-associated UTI - can disseminate to multiple organs ----------------------- mucocutaneous: - Nystatin - oral or topical azoles systemic: - azoles - Echinocandins - Amphotericin B
Candida glabrata
Morphology
Transmission and Reservoir
Diseases
Treatment and Prevention
yeast
- mouth, skin, GI tract, vagina
- occurs when there is a breach in the host immune defense
- seen when C. albicans is decreased by fluconazole treatment
- oral thrush
- esophagitis
- vaginitis
- bloodstream infection
- abscesses
- same as Candida albicans
Cryptococcus neoformans
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Diagnosis Treatment and Prevention
yeast ----------------------- - soil contaminated by bird droppings - inhalation - immunocompromised hosts ----------------------- - polysaccharide capsule - melanin to protect against oxidative stress ----------------------- 1) inhaled 2) travels to CNS and other organs ----------------------- pneumonia meningoencephalitis - occurs in up to 10% of people with AIDS - persistent, dull headache, malaise, fever, night sweats, meningeal signs may or may not be present skin & bloodstream infections ----------------------- - India ink stain of CSF - Cryptococcal antigen test on blood or CSF: measuring polysaccharide antigen by ELISA or latex agglutination - CSF culture ----------------------- - Amphotericin B + 5-flucytosine, followed by fluconazole
Cryptococcus gattii
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Diagnosis Treatment and Prevention
yeast ----------------------- -inhalation - tropical areas ----------------------- - polysaccharide capsule - melanin to protect against oxidative stress ----------------------- 1) inhaled 2) travels to CNS and other organs ----------------------- pneumonia meningoencephalitis skin & bloodstream infections ----------------------- - stain w/ India ink ----------------------- - same as Cryptococcus neoformans
Pneumocystis jiroveci (Pneumocystis carinii)
Morphology
Transmission and Reservoir
Diseases
Diagnosis
Treatment and Prevention
yeast
lacks ergosterol ----------------------- - inhalation of cyst in childhood - reactivation when immunocompromised ----------------------- Pneumocystis jiroveci Pneumonia (PJP) - gradual onset of fever, dyspnea, and non-productive cough ----------------------- - CXR with bilateral interstitial infiltrates, rarely focal or cavitary ----------------------- - TMP/SMX
Aspergillus flavus
Morphology
Transmission and Reservoir
Virulence Factors
Diseases
Diagnosis
Treatment and Prevention
mold ----------------------- - rotting plants - inhalation ----------------------- aflatoxin B1 is a powerful carcinogen ----------------------- ----------------------- hepatocellular carcinoma ----------------------- - branching, septate hyphae ----------------------- - Amphotericin - Voriconazole - Posaconazole - Itraconazole - Echinocandins
Aspergillus perasiticus
Morphology
Transmission and Reservoir
Virulence Factors
Diseases
Diagnosis
Treatment and Prevention
mold ----------------------- - rotting plants - inhalation ----------------------- aflatoxin B1 is a powerful carcinogen ----------------------- ----------------------- hepatocellular carcinoma ----------------------- - branching, septate hyphae ----------------------- same as A. flavus: - Amphotericin - Voriconazole - Posaconazole - Itraconazole - Echinocandins
Aspergillus fumigates
Morphology
Transmission and Reservoir
Pathogenesis
Diseases
Diagnosis
Treatment and Prevention
mold
- rotting plants
- inhalation
- 1) inhalation of spores
2) evasion of pulmonary macrophages or neutrophils
3) local infection in the lung
4) entry into blood vessels
5) dissemination to other sites (e.g. brain) - airway colonization
- allergic bronchopulmonary aspergillosis (ABPA)
- treacheobronchitis
- sinusitis
- aspergilloma (fungus ball)
- invasive pulmonary aspergillosis
- disseminated aspergillosis
- branching, septate hyphae
- same as A. flavus
Aspergillus niger
Morphology Transmission and Reservoir Diseases Diagnosis Treatment and Prevention
mold ----------------------- - rotting plants - inhalation ----------------------- chronic otitis externa ----------------------- - branching, septate hyphae ----------------------- - same as A. flavus
Zoophilic Dermatophyte:
Microsporum canis
Morphology
Transmission and Reservoir
Pathogenesis
Diseases
Diagnosis
Treatment and Prevention
mold ----------------------- - animals - contact ----------------------- infect keratinized layer of skin ----------------------- tinea corpis (ring worm), tinea capitis (scalp infection) ----------------------- - skin scrapings or nail clippings can be examined microscopically or cultured - fluoresces green under UV light ----------------------- - Imidazoles - Terbinafine - Azoles
Anthropophilic Dermatophyte:
Trichophyton rubrum
Morphology
Transmission and Reservoir
Pathogenesis
Diseases
Diagnosis
Treatment and Prevention
mold ----------------------- - humans - contact ----------------------- infect keratinized layer of skin ----------------------- tinea pedis (athlete’s foot), tinea cruris (jock itch) ----------------------- - skin scrapings or nail clippings can be examined microscopically or cultured
- Imidazoles
- Terbinafine
- Azoles
Zygomycetes: Mucor Absidia Rhizopus Rhizomucor
Morphology Transmission and Reservoir Diseases Diagnosis Treatment and Prevention
mold ----------------------- - inhalation - risk factors: immune deficiency, diabetes, hemochromatosis ----------------------- pneumonia sinusitis brain abscess thrombosis infarction ----------------------- - non-septate hyphae that branch at right angles ----------------------- - Amphotericin B - Posaconazole
Sporothrix schenckii
Morphology
Transmission and Reservoir
Diseases
dimorphic fungi
(mold at ambient temperature, yeast at 37C)
———————–
soil, infected plant products, wood, roses
- puncture wound
———————–
cutaneous disease with local lymphatic spread
Histoplasma capsulatum
Morphology
Transmission and Reservoir
Pathogenesis
Diseases
dimorphic fungi ----------------------- - soil in Mississippi & Ohio River Valleys - inhalation ----------------------- -disseminated from respiratory tract ----------------------- histoplasmosis pulmonary infection; can be disseminated
Coccidioides spp.
Morphology
Transmission and Reservoir
Pathogenesis
Diseases
dimorphic fungi ----------------------- -soil in SW US - inhalation - no person-to-person transmission ----------------------- 1) mycelia (infectious) form in soil 2) spores within humans convert to spherules 3) spherules rupture and release endospores, which form more spherules - disseminated from respiratory tract ----------------------- valley fever: - can be asymptomatic - primary disease usually resolves spontaneously - immunocompromised patients are more susceptible to chronic or disseminated infection - complications: 1) cavity formation 2) dissemination to skin 3) meningitis 4) pneumonia
Blastomyces dermatitidis
Morphology
Transmission and Reservoir
Pathogenesis
Diseases
dimorphic fungi ----------------------- - soil in Mississippi & Ohio River Valleys - inhalation - ----------------------- disseminated from respiratory tract ----------------------- blastomycosis: pulmonary infection that spreads to skin and bone
Dermatiaceous molds
Morphology
Diseases
mold
cutaneous & subcutaneous infection,
fungal meningitis
Penicillium marneffei
Transmission and Reservoir
- SE Asia
- immunocompromised hosts
Fusarium
Transmission and Reservoir
- patients with hematological malignancies and bone marrow transplantation
Scedosporium
Transmission and Reservoir
- post-traumatic infection in immunocompetent
- disseminated infection in immunocompromised
Entamoeba histolytica
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases
Treatment and Prevention
protazoa ----------------------- - fecal-oral - contaminated food or water - rarely found in US ----------------------- - cysts ----------------------- 1) cyst is excreted by a person 2) fecally contaminated food or water is ingested 3) becomes a trophozoites in the gut and attaches to colonic mucosa 4) may penetrate mucosa and travel to the liver via the portal circulation, forming liver abscesses 5) more cysts are formed in the gut and shed ----------------------- bloody diarrhea liver abscess incubation time of 2-4 weeks ----------------------- Metronidazole
Acanthamoeba
Morphology
Transmission and Reservoir
Diseases
protozoa ----------------------- - contaminated water - contact lenses ----------------------- lens opacity; can lead to blindness
Naegleria fowleri
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Diagnosis Treatment and Prevention
protazoa
- warm freshwater & soil
- southern US
- enters the nose when swimming
- brain infection
- fatal
Giardia
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Diagnosis Treatment and Prevention
protazoa
- reservoir: wild animals, farm animals, pets
- fecal-oral
- contaminated water or food
- occurs in US
- IgA deficiency is pre-disposing factor
- cysts
- 1) trophozoites multiply in duodenum
2) cysts form in colon and are excreted
3) intestinal inflammation and malabsorption of fats and carbohydrates - explosive diarrhea involving foul-smelling, greasy stool
- significant weight loss in children
- chronic diarrhea in adults
- relapses are common
- incubation time: 1-4 weeks
- trophozoites or cysts in stool
- Metronidazole
Cryptosporidium parvum
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Diagnosis Treatment and Prevention
protazoa
- reservoir: farm animals, pets
- fecal-oral
- contaminated water
- occurs in US
- oocysts
- 1) sporozoites penetrate enterocytes and develop into trophozoites
2) oocytes form and are shed in stool
3) inflammation and malabsorption - ranges from mild diarrhea to severe dysentery in immunocopromised
- relapses can occur
- 5-10 day incubation
- oocysts in stool
- modified acid-fast stain
- Nitazoxanide
Microsporidia
Morphology
Transmission and Reservoir
Diseases
protazoa ----------------------- - affects immunocompromised - occurs in US ----------------------- diarrhea
Trichomonas vaginalis
Morphology Transmission and Reservoir Diseases Diagnosis Treatment and Prevention
protazoa ----------------------- - STD - occurs in US ----------------------- asymptomatic in men; vaginal discharge with fish-like odor in women ----------------------- - pear-shaped, flagellated organisms with characteristic twitching motility ----------------------- - Metronidazole
Plasmodium
(vivax, ovale, and falciparum)
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Diagnosis Treatment and Prevention
- mosquito bites
- occurs outside of US
- vivax & ovale found in temperate zones (mosquitoes during warmer months)
- falciparum found in tropical regions (mosquitoes year round)
- sickle cell anemia is protective
- ## unexposed people are most susceptible-PfEMP in falciparum: variable protein that can cause binding of RBC to many different host proteins; causes RBC sequestration and obstruction to tissue perfusion; avoids clearance by the spleen
———————–
1) sporozoites from mosquito infect humans
2) travel to liver and invade hepatocytes
3) differentiate into tissue schizonts and multiply
4) live in the liver as latent hypnozoites (only occurs in vivax & ovale)
5) differentiate into merozoites and exit hepatocytes
6) merozoites invade RBCs (falciparum can invade RBCs of any age, but vivax & ovale only invade reticulocytes)
7) RBCs lyse and release merozoites
8) some differentiate into gametocytes and are taken up by mosquitoes to complete the cycle - ## cyclic fevers occur b/c RBCs lyse to release merozoites every 48 hoursmalaria - vivax & ovale
- cyclic fevers
severe malaria - falciparum - 7-90 day incubation
- cyclic or non-cyclic fevers
- microvascular disease
- hypoglycemia
- cerebral malaria
- renal failure
- pulmonary edema
- anemia
- multiorgan failure
- ## coma
- blood smear
- ## rings only seen with falciparum
- Chloroquine: usually ineffective due to resistance
- Quinine
- Primaquine: only drug active against hypnozoites
- Artemisinin derivatives: use for resistant strains as combination therapy
- Mefloquine (Lariam): prophylaxis & treatment
- Atovaquone/ proguanil (Malarone): prophylaxis & treatment
Babesia
Morphology
Transmission and Reservoir
Pathogenesis
Diseases
Diagnosis
protazoa
- reservoir: deer & white-footed mice
- vector: ticks
- asplenia is a risk factor
- NE US, Nantucket Island, Martha’s Vineyard, Cape Cod
- infects erythrocytes Babesiosis (malaria-like disease)
- Maltezer cross
Leishmania
Morphology
Transmission and Reservoir
Pathogenesis
Diseases
protazoa ----------------------- - vector: sandflies - found in Central and South America, Middle East, and Africa ----------------------- - invade macrophages in humans ----------------------- cutaneous leishmaniasis visceral leishmaniasis (kala azar): - fevers - hepatosplenomegaly
Trypansoma cruzi
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases
protazoa ----------------------- - kissing bugs - contaminated fruit juice - blood transfusions - mother-to-child transmission - Central and South America ----------------------- - does not undergo antigenic shift - evades complement - escapes phagosome to live in cytoplasm ----------------------- - blood stage and intracellular stage (in phagosomes) ----------------------- Chagas disease - esophageal and colon dysmotility - cardiomyopathy
Trypansoma brucei
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Diagnosis Treatment and Prevention
protazoa
flagellated ----------------------- - tsetse fly - Africa ----------------------- - variable surface glycoprotein (VSG): covers surface; antigenic shift through gene conversion ----------------------- - extracellular parasite - spreads systemically ----------------------- African sleeping sickness - stage 1: lymphadenopathy, fever, anemia, edema, rash - stage 2: meningoencephalitis, CNS symptoms including sleeping during the day, coma, death
Toxoplasma gondii
Morphology
Transmission and Reservoir
Pathogenesis
Diseases
Diagnosis
Treatment and Prevention
protazoa
obligate intracellular
- found in cat feces & undercooked meat
- can cross the placenta
- reactivation in T-cell immunocompromised patients -
- 1) infected rodents are eaten by cats
2) parasites undergo sexual cycle in cats
3) sporozoites in cat feces are ingested by humans
4) sporozoites penetrate the intestinal wall
5) tachyzoites (replicative form) infect macrophages)
6) disseminate via hematogenous spread
7) can cross the placenta
8) can form cysts with bradyzoites (latent form) in brain
9) if immunocompromised, cysts can release tachyzoites into brain and induce inflammation - common latent infection in many countries
- congenital toxoplasmosis - acute infection during pregnancy can lead to retinitis & CNS disease in babies
- Toxoplasma encephalitis or ocular toxoplasmosis in immunocompromised (e.g. AIDS patients)
- head CT shows ring-like structure in brain
- TMP/SMX
Enterobius vermicularis
(Pinworm)
Morphology
Transmission and Reservoir
Diseases
Treatment and Prevention
intestinal nematode ----------------------- - ingestion of infective eggs - not associated with any specific socioeconomic level ----------------------- perianal itch ----------------------- - Albendazole / Mebendazole - Pyrantel
Necator americanis
(Hookworm
Morphology
Transmission and Reservoir
Diseases
intestinal nematode ----------------------- - penetration of skin by larval forms - impoverished rural areas ----------------------- itchy feet with rash anemia
Ancylostoma duodenale
(Hookworm)
Morphology
Transmission and Reservoir
Diseases
intestinal nematode ----------------------- - penetration of skin by larval forms - impoverished rural areas ----------------------- itchy feet with rash anemia
Trichuris trichiura
Whipworm
intestinal nematode - ingestion of infective eggs
- impoverished rural areas - - non-specific abdominal discomfort and/or anemia - - Albendazole / Mebendazole
- Ivermectin
Ascaris lumbricoides
Morphology
Transmission and Reservoir
Diseases
Treatment and Prevention
intestinal nematode ----------------------- - ingestion of infective eggs - impoverished rural areas ----------------------- non-specific abdominal discomfort and/or anemia
Albendazole / Mebendazole
Ivermectin
Onchocerca
Morphology
Transmission and Reservoir
Pathogenesis
Diseases
Treatment and Prevention
tissue nematode (filaria) ----------------------- - mosquito/ insect bite - non-US ----------------------- infection of lymphatics ----------------------- river blindness ----------------------- Ivermectin
Wucheria
Morphology
Transmission and Reservoir
Pathogenesis
Diseases
tissue nematode (filaria) ----------------------- mosquito/ insect bite - non-US - ----------------------- infection of lymphatics ----------------------- elephantiasis
Brugia
Morphology
Transmission and Reservoir
Pathogenesis
Diseases
tissue nematode (filaria) ----------------------- mosquito/ insect bite - non-US - ----------------------- infection of lymphatics ----------------------- elephantiasis
Trichinella
Morphology
Transmission and Reservoir
Pathogenesis
Diseases
tissue nematode (filaria) ----------------------- - contaminated food (undercooked pig, boar, or bear meat) - occurs in US ----------------------- 1) ingestion 2) migrate through intestine 3) migrate to muscles 4) immune-mediated inflammatory reaction ----------------------- fever, myalgias, edema 3-30 day incubation
Schistosoma spp.
Morphology
Transmission and Reservoir
Pathogenesis
Diseases
Treatment and Prevention
- grow in snails
- skin contact with contaminated water
- ## occurs everywhere except North America, Europe, & Australiasnail → fresh water → human skin → lungs & liver → GI tract or bladder
———————–
acute schistosomiasis: Katayama fever
chronic schistosomiasis:
liver disease, hematuria, bladder cancer, neurologic disease
———————–
eggs in urine (S. hematobium) or feces (S. japonicum or mansoni)
Taenia solium
Morphology
Transmission and Reservoir
Diseases
Treatment and Prevention
tapeworm (cestode) ----------------------- - reservoir: pigs - ingestion of T. solium eggs or undercooked pork ----------------------- cysticercosis neurocysticercosis (seizures) ----------------------- Albendazole/ Mebendazole
Taenia saginata
Morphology
Transmission and Reservoir
Diseases
tapeworm (cestode) ----------------------- - reservoir: cows - ingestion of undercooked beef - ----------------------- abdominal symptoms - -
Echinococcus
Morphology
Transmission and Reservoir
Pathogenesis
Diseases
Treatment and Prevention
tapeworm (cestode) ----------------------- - reservoir: dogs - dog fecal-oral ----------------------- 1) ingestion of eggs 2) eggs hatch to form oncospheres that penetrate the intestinal mucosa and enter the circulation 3) cysts formin organs, particularly the liver ----------------------- Hydatid disease - liver cysts ----------------------- Albendazole / Mebendazole
Lice
Morphology
Diseases
Treatment and Prevention
ectoparasite ----------------------- nits - scalp hair infestation body lice - body hair infestation crabs - pubic hair infestation ----------------------- Ivermectin - Permethrin - Malathion
Sarcoptes scabei
Morphology
Diseases
Treatment and Prevention
ectoparasite ----------------------- scabies - itchy rash between fingers ----------------------- Ivermectin - Permethrin
maggots
Morphology
Diseases
myiasis (maggots under the skin)
new variant Creutzfeldt-Jakob disease (vCJD)
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases
prion ----------------------- - consumption of BSE meat contaminated with brain tissue or the consumption of brain tissue itself ----------------------- - PrPsc ----------------------- PrPsc (abnormal prion protein) accumulates in the brain ----------------------- CNS degeneration, death
kuru
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases
prion ----------------------- - tribe members in New Guinea eating human brains ----------------------- - PrPsc ----------------------- PrPsc (abnormal prion protein) accumulates in the brain ----------------------- CNS degeneration, death
bovine spongiform encephalopathy (BSE) (mad cow disease)
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases
prion ----------------------- - consumption of bone meal made from diseased cows - occurs in cows ----------------------- - PrPsc ----------------------- PrPsc (abnormal prion protein) accumulates in the brain CNS degeneration, death
scrapie
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases
prion ----------------------- - occurs in sheep ----------------------- - PrPsc ----------------------- PrPsc (abnormal prion protein) accumulates in the brain ----------------------- CNS degeneration, death
chronic wasting disease
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases
prion ----------------------- - occurs in deer & elk ----------------------- - PrPsc ----------------------- PrPsc (abnormal prion protein) accumulates in the brain ----------------------- CNS degeneration, death
Streptococcus agalactiae
(Group B)
Morphology
Transmission and Reservoir
Virulence Factors
Diseases
Gram+ cocci
β-hemolytic
- ## human reservoir (colonize female genital tract)
- ## capsule: binds factor H and makes C5a-degrading enzymeneonatal sepsis & meningitis
Streptococcus pneumoniae
(pneumococcus)
(no Lancefield group)
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Treatment and Prevention
Gram + cocci
alpha-hemolytic
extracellular ----------------------- - human reservoir (colonize upper respiratory tract) - transmission by respiratory droplets & close contact ----------------------- 1) polysaccharide capsule: prevents phagocytosis; doesn’t bind factor B, so the alternative complement pathway isn’t activated 2) IgA protease 3) pneumolysin O: causes plasma membrane lysis; damages bronchi, ciliated cells, and alveoli, promoting inflammation and spread 4) neuraminidase: cleaves sialic acid to open site for attachment 5) lipoteichoic acid (LTA): promotes IL-1 and TNF- release 6) altered PBP: leads to -lactam resistance, but can usually be overcome by increasing drug dose ----------------------- 1) colonize 2) move to lower airway by aspiration 3) enter bloodstream from pharynx or lung ----------------------- respiratory tract - sinusitis - otitis media - conjunctivitis - bronchitis - CA-pneumonia disseminated - bacteremia - endocarditis - meningitis - peritonitis - septic arthritis - osteomyelitis ----------------------- 1) Macrolides 2) Tetracyclines 3) Moxifloxacin 4) Levofloxacin
Viridans streptococci spp.
(usually no Lancefield group)
Morphology
Transmission and Reservoir
Diseases
Gram+ cocci
alpha-hemolytic or γ-hemolytic
extracellular
- human reservoir (colonize upper respiratory tract, colon, and female genital tract)
- dental caries
- endocarditis
- abscesses
Enterococcus
faecalis
(Group D)
Morphology Transmission and Reservoir Virulence Factors Diseases Treatment and Prevention
Gram+ cocci
alpha- or γ-hemolytic
extracellular ----------------------- - human reservoir (GI tract, skin of hospitalized patients) - spread by contact ----------------------- - alteration in cell wall leads to Ampicillin & Vancomycin resistance ----------------------- - bacteremia - endocarditis - UTI - surgical site infections - abscesses ----------------------- “Learn VRE Drugs for Test Now.” 1) Linezolid 2) Daptomycin 3) Tigecycline 4) Nitrofurantoin - contact precautions for VRE
Enterococcus faecium
Morphology Transmission and Reservoir Virulence Factors Diseases Treatment and Prevention
Gram+ cocci
extracellular
- same as E. faecalis
- same as E. faecalis
- more likely than faecalis to be Vancomycin-resistant
- same as E. faecalis
- same as E. faecalis
Staphylococcus aureus
(USA300 is a common cause of CA-MRSA)
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Treatment and Prevention
Gram+ cocci
β-hemolytic
- human reservoir (colonize warm, moist areas)
- ## transmission through fomites, contact, and eating contaminated foodExotoxins
1) hemolysin -γ (includes toxin)
2) enterotoxins A-J: act as superantigens and cause diffuse immune activation
3) heat-stable enterotoxin - superantigen involved in food poisoning
4) exfoliative epidermolytic toxin A/B: superantigens that cause skin to slough off
5) toxic shock syndrome toxin (TSST-1): superantigen that stimulates 20% of T cells and causes secretion of IL-2 and TNF-
6) Panton-Valentine Leukocidin: cytotoxin associated with CA-MRSA; probably just a genetic marker for other virulence factors
Adherence - MSCRAMMs
1) protein A: binds Ig via Fc portion, coating membrane without causing phagocytosis
2) clumping factor A/B: bind fibrinogen
3) collagen binding protein
4) fibronectin binding protein A/B
5) plasmin-sensitive protein: promotes binding to nasal epithelial cells
Cell Wall Components
1) polysaccharide capsule: inhibits phagocytosis
2) peptidoglycan: provides anchor for MSCRAMMs; triggers cytokine release
3) LTA: pro-inflammatory; stimulates cytokine release
4) β-lactamases
5) MecA: altered PBP that causes MRSA; gene found on Staphylococcal Chromosomal
Cassette (SCC); SCCMecIV IV associated with CA-MRSA
Biofilms
Quorum-Sensing and Two-Component Regulatory Systems - AIP (auto-inducer) AgrC (membrane sensor) AgrA (transcriptional regulator) transcription of toxin genes
- ## AIP from one strain can competitively inhibit AgrC from another strain
- ## bacterial intoxication in TSS and food poisoningskin and soft tissue disease
- abscess
- cellulitis
- myositis
- osteomyelitis
- septic arthritis
- necrotizing fasciitis
disseminated disease - bacteremia
- endocarditis
- toxic shock syndrome: fever, rash, hypotension, confusion, renal failure, vomiting, diarrhea
device infections - central venous catheters
food poisoning - 1-6 hour incubation time
- ## vomiting“Drugs to Confidently Treat Very Lethal Commensals”
1) Daptomycin
2) TMP/SMX
3) Ceftaroline
4) Tetracycline/ Tigecycline
5) Vancomycin
6) Linezolid
7) Clindamycin - contact precautions for MRSA
coagulase- staphylococcus
(e.g. S. saprophyticus)
Morphology
Diseases
Gram + cocci
extracellular
- vascular line-associated bacteremia
- cystitis in women (S. saprophyticus)
coagulase- staphylococcus
(e.g. S. saprophyticus)
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases
Gram+ spore-forming rod
extracellular
aerobic ----------------------- - fecal-oral - contaminated food ----------------------- - heat-stable emetic enterotoxin ----------------------- bacterial intoxication ----------------------- food poisoning - 1-6 hours incubation time - vomiting
Bacillus cereus (non-emetic form)
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases
Gram+ spore-forming rod
extracellular
aerobic ----------------------- - fecal-oral - contaminated food ----------------------- - heat-labile diarrheal enterotoxin ----------------------- production of enterotoxin in vivo ----------------------- food poisoning - 12 hour incubation time - diarrhea, cramps
Bacillus anthracis
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Diagnosis Treatment and Prevention
Gram+ spore-forming rod
extracellular
aerobic
- cattle, sheep, goats
- no person-to-person transmission
cutaneous - spores enter cutaneous abrasion
inhalation - inhalation of spores
GI - ## ingestion of uncooked meat
- poly-D glutamic acid capsule: anti-phagocytic
- protective antigen (PA): binds to host cell receptors and LF and EF
- lethal factor (LF): toxin that is a protease
- edema factor (EF): toxin that activates adenylate cyclase to increase cAMP in host cells
- capsule encoded by pXO2 plasmid
- ## exotoxins (LF and EF) encoded by pXO1 plasmid1) germination of the spore
2) multiplication and toxin production
3) may stay contained in the skin or spread through the
bloodstream and lymphatics
3) causes inflammation of lymph nodes
———————–
cutaneous anthrax: - 1-7 day incubation
- pruritic papule vesicle black eschar
- enlarged lymph nodes
inhalation anthrax (Woolsorter’s Disease): - 4-6 day incubation
- flu symptoms w/o runny nose
- bloody pleural effusions
- mediastinal widening due to enlarged lymph nodes
- hemorrhagic meningitis
- 45% fatality if recognized and treated early
GI anthrax: - 1-5 day incubation
- GI symptoms
- ## 40% mortality
- medusa’s head/comet tail colonies on blood agar
- box car appearance on Gram stain
- Doxycycline
- Ciprofloxacin
- Raxibacumab
Clostridium botulinum
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Treatment and Prevention
Gram + spore-forming rod
anaerobic
tennis racket appearance of Gram stain
- ingestion of contaminated food (e.g. honey, home-cooked food)
- colonization of GI tract or wound
- ## no person-to-person transmission
- botulinum toxin: prevents release of ACh by cleaving neuronal proteins involved in synaptic vesicle docking; acts at neuromuscular junction
- serotype A is most serious because it persists longest in the neuron
- ## serotype E also causes vomiting
- usually a bacterial intoxication
- infant botulism and adult infant botulism are caused by C. botulinum that colonizes the GI tract and produces toxins in vivo
- wound botulism: C. botulinum enters wound and produces toxin in vivo
- ## toxin spreads to CNSbotulism
- 12-72 hour incubation
- double vision
- swallowing difficulties
- descending flaccid paralysis
- breathing problems
- infants first present with constipation
- ## 70% fatality if untreated; 10% fatality if treated
- anti-toxin
Clostridium perfringens
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases
Gram + spore-forming rod
anaerobic
extracellular ----------------------- - found in soil, GI tract, & contaminated food - puncture wound or ingestion of contaminated food ----------------------- - alpha toxin: phospholipase C that disrupts plasma membranes - β toxin: forms pores - heat-labile enterotoxin: damages membranes ----------------------- - toxin production in vivo ----------------------- gas gangrene, anaerobic cellulitis wound infections organ infections bacteremia food poisoning - 12 hour incubation - diarrhea, cramps
Clostridium septicum
Morphology
Transmission and Reservoir
Diseases
Gram + spore-forming rod
anaerobic
extracellular ----------------------- - found in GI tract ----------------------- infections in patients with cancer of the GI tract
Clostridium difficile
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Diagnosis Treatment and Prevention
Gram + spore-forming rod
anaerobic
- GI tract
- ## ingestion
- toxin A: monoglucosyltransferase; interferes with actin cytoskeleton to make intestinal epithelial cells leaky; attracts neutrophils and stimulates the release of cytokines; causes inflammation
- toxin B: same mechanism as toxin A; also induces cytopathic effect in tissue culture cells
- ## binary toxin: disrupts actin cytoskeleton; only found in some isolates; more frequent in patients w/ more severe disease1) use of antibiotics disrupts the gut flora
2) ingestion
3) colonization in gut
4) toxin production leads to diarrhea
5) pseudomembranous inflammation
———————–
diarrhea in hospitalized patients; spectrum from asymptomatic carriage to toxic megacolon and death; relapse may occur
———————– - ## detection of toxins is gold standard for diagnosis“Very Fun Medications”
1) Vancomycin
2) Fidaxomicin
3) Metronidazole - use soap and water, not alcohol, to remove spores
Clostridium tetani
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Treatment and Prevention
Gram+ spore-forming rod
anaerobic
extracellular ----------------------- - soil - puncture wound or contaminated umbilical stump ----------------------- - tetanus neurotoxin/tetanospasmin: inhibits release of inhibitory neurotransmitter glycine by cleaving neuronal proteins involved in synaptic vesicle docking; works on CNS in spinal cord ----------------------- toxin migrates along motor neurons into CNS ----------------------- tetanus - incubation time up to months - spastic paralysis - death by respiratory failure neonatal tetanus ----------------------- - tetanus antitoxin
Corynebacterium diphtheriae
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Diagnosis Treatment and Prevention
Gram+ rod
- human reservoir
- aerosol droplets
- inhalation leads to nasopharyngeal diphtheria
- ## infection of a wound leads to cutaneous diphtheria
- diphtheria toxin: ADP-ribosylates elongation factor 2 (EF-2), causing inhibition of host protein synthesis and cell death
- tox gene encodes diphtheria toxin and is carried by the β phage which lysogenically infects C. diptheriae
- expression of diphtheria toxin only occurs under low-iron conditions
- high iron: diphtheria toxin repressor (DtxR) binds iron, forms dimer, and inhibits transcription of the tox gene
- low iron: DtxR cannot bind iron and dimerize, so the tox gene is expressed
- DtxR is encoded by the bacterial chromosome
- ## adhesins: necessary for colonization1) colonizes nasopharynx or skin
2) produces diphtheria toxin
3) necrosis and formation of a pseudomembrane
4) toxin can travel through the blood and damage organs
———————–
diphtheria - 1-7 day incubation
- malaise, sore throat, enlarged cervical lymph nodes
- gray pseudomembrane over tonsils and throat
- pseudomembrane can lead to suffocation
- ## dissemination of diphtheria toxin can lead to damage of internal organs (e.g. the heart) and death
- microscopy: club-shaped rods that are arranged in palisades or Chinese character formations; polyphosphate granules
- isolate on media containing tellurite salts
- ## toxin testing to differentiate from non-toxigenic strains
- antitoxin + antimicrobials
Listeria monocytogenes
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Diagnosis Treatment and Prevention
Gram+ rod
intracellular
β-hemolytic
optimal growth at 30C-37C, but can grow at 4C
- soil, decaying vegetation
- intestinal tract of many animals, including cattle
- processed foods that are not re-heated
- Listeriolysin O (gene hlyA): breaks open the phagosome and allows the bacterium to enter the cytoplasm
- actA gene: allows Listeria to nucleate host actin to form a tail, which can propel it into neighboring cells
- 1) enters GI tract through ingestion
2) multiplies in liver
3) spreads to brain and/or placenta via bloodstream - invades cells through zipper mechanism
- induces inflammation
- incubation time of several days
- influenza-like disease
- neonatal meningitis
- meningoencephalitis or bacteremia in immunocompromised
- infection during pregnancy can result in spontaneous abortion, stillbirth, premature labor, or newborn with high bacterial load
- monocytes/ macrophages in CSF
- Ampicillin +/- Sulbactam
- Amoxycillin +/- Clavulanate
Nocardia
Morphology
Treatment and Prevention
Gram+ rod
branching filaments
———————–
- TMP/SMX
Moraxella catarrhalis
Morphology
Diseases
Treatment and Prevention
Gram- diplococci ----------------------- community-acquired pneumonia ----------------------- - macrolides - tetracyclines
Neisseria gonorrhoeae
Morphology Transmission and Reservoir Virulence Factors Diseases Treatment and Prevention
Gram- diplococci inside of neutrophils ----------------------- - human reservoir - STD ----------------------- - pili: attachment to urogenital tract (phase variation and antigenic shift due to gene conversion) - Opa proteins: increase adherence (phase and antigenic variation) - LOS (phase and antigenic variation) - IgA protease ----------------------- males - urethritis with purulent discharge female - may be asymptomatic - cervicitis - urethritis female complications - PID - infertility - conjunctivitis in babies ----------------------- - macrolides - tetracyclines
Neisseria meningitidis
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Treatment and Prevention
Gram- diplococci inside of neutrophils
- human reservoir
- meningococcal belt in Africa during Dec-June
- polysaccharide capsule: avoidance of immune response; many serotypes
- serotype B capsule: identical to human neuronal sialic acid
- outer membrane proteins: attachment to CD24 and fibronectin; antigenic variation
- pili: attachment, invasion, passage through blood-brain barrier; antigenic variation
- LOS: pro-inflammatory
- IgA protease: cleaves IgA
- fHbp: binds factor H
- 1) attach to the epithelium of the pharynx via pili and outer membrane proteins
2) invade epithelial cells
3) enter vascular space, rapidly multiply, and release LOS
4) circulate to distant sites
5) cause meningitis in the brain
6) cause purpura in the skin - many carriers
- meningitis (fever, headache, neck stiffness)
- purpura or petechiae
- Rifampin
Commensal Neisseria
Morphology
Virulence Factors
Diseases
Gram- diplococci
- no capsule or pili
- colonize oral and GI tract, but do not cause disease
Enterotoxigenic E. coli (ETEC)
(O148:H28)
Enterobacteriaceae
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Treatment and Prevention
- human reservoir
- ## contaminated food or water
- common/type 1 pilli: attach to mannose receptors on host surfaces; phase variation
- siderophores: have high affinity for iron
- LPS: endotoxin
- CFAI/II/III: unique pilli used for colonizing the intestine
- heat stable enterotoxin
(STa): increases
intestinal cGMP to stimulate fluid & electrolyte secretion - heat labile enterotoxin (LT): increases intestinal cAMP
- ## CFA and enterotoxin genes are on a single plasmid
- colonize small intestine
- multiply and produce enterotoxins in vivo
- ## toxins increase intestinal fluid secretion
- watery diarrhea in infants and travelers to regions with poor sanitation
- ## 16-72 hour incubation time
- Ampicillin +/- Sulbactam
- Amoxycillin +/- Clavulanate
- 1st and 2nd generation cephalosporins
- Nitrofurantoin
Enteropathogenic E. coli (EPEC)
(O26:H11)
Enterobacteriaceae
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Diagnosis Treatment and Prevention
Gram- enteric rod
- human reservoir
- contaminated food or water
- common/type 1 pilli
- siderophores
- LPS
- bfp
- TIR
- intimin
- EPEC adheres to enterocytes using bundle-forming pillus (bfp)
- delivery of effectors (TIR intimin receptor) via type III secretion system
- TIR inserts into host membrane
- bacterial intimin binds to TIR
- actin polymerization occurs in the host cell, creating a pedestal
- infant diarrhea in developing countries
- attaching and effacing lesions visible on biopsy
- same as ETEC
Enteroaggregative E. coli (EAEC)
Enterobacteriaceae
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Treatment and Prevention
Gram- enteric rod
- human reservoir
- contaminated food or water
- common/type 1 pilli
- siderophores
- LPS
- EAST
- shiga toxin (recent outbreak)
- biofilms
- adherence to enterocytes as aggregates composed of many bacterial cells
- increase mucus production, resulting in trapping of bacteria in biofilm
- make EAST (enteroaggregative-like stable toxin)
- cause watery discharge and subtle inflammation
- in a recent outbreak, a strain produced shiga toxin
- chronic diarrhea in HIV+ individuals in developing countries
- infant diarrhea in US
- acute traveler’s diarrhea
- low grade fever may occur
- HUS in adults if it produces shiga toxin
- same as ETEC
Enteroinvasive
E. coli (EIEC)
Enterobacteriaceae
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Treatment and Prevention
Gram- enteric rod
- human reservoir
- contaminated food or water
- common/type 1 pilli
- siderophores
- LPS
- afimbrial adhesions
- type III secretion system
- invade enterocytes
- lyse endocytic vesicles and escape into the cytoplasm
- multiply and cause cell destruction
- watery diarrhea, sometimes with blood and fecal leukocytes
- same as ETEC
Enterohemorrhagic E. coli (EHEC)
(O157:H7)
Enterobacteriaceae
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Treatment and Prevention
Gram- enteric rod ----------------------- - human reservoir - contaminated food - infected animals - swimming pools w/ inadequate chlorination ----------------------- - common/type 1 pilli - siderophores - LPS - bfp - TIR - intimin - shiga toxin: inactivates 60S ribosomal subunit, causing inhibition of protein synthesis; kidney cells are sensitive (essentially EPEC + shiga toxin) ----------------------- - close adherence via intimin - production of shiga toxin in vivo - shiga toxin causes colonic damage and can be absorbed into the circulation and affect the kidneys ----------------------- - 15-48 hour incubation time - hemorrhagic colitis - hemolytic uremic syndrome (HUS): kidney failure, usually in children ----------------------- - same as ETEC - antibiotics contra-indicated in HUS
Uropathogenic
E. coli (UPEC)
(O4:H5)
Enterobacteriaceae
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Treatment and Prevention
Gram- enteric rod ----------------------- - human GI tract - spread from rectum ----------------------- - common/type 1 pilli - siderophores - LPS - P pilli/pap pilli: able to bind to P blood group / Forssman antigen on renal epithelium; phase variation - hemolysin: forms pores; damages kidney cells ----------------------- - can be invasive ----------------------- UTI - cystitis - pyelonephritis ----------------------- - same as ETEC
E. coli
(K1)
Enterobacteriaceae
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Treatment and Prevention
Gram- enteric rod
- human reservoir
- common/type 1 pilli
- siderophores
- LPS
- sialic acid capsule: inhibits phagocytosis and complement activation; molecular mimicry
- endotoxin induces symptoms (fever, shock, etc.)
- neonatal / childhood meningitis
- same as ETEC
Non-Typhoid Salmonella
Enterobacteriaceae
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Diagnosis
- reservoir: nearly all common food animals, pets including turtles
- contaminated food
- contaminated water
- person-to-person spread by fecal-oral route
- ## some human carriers
- Inv/Spa type III secretion system: promotes entry into intestinal epithelial cells
- Spi/Ssa type III secretion system: contributes to survival inside macrophages
- Sip: transferred to host cell surface; induces membrane ruffling
- invasion genes are chromosomal
- LPS: inflammation
- two component regulatory system
- PhoQ: membrane sensor; activated by low Mg+2 inside of phagocytes
- PhoP: transcriptional regulator
- pag genes: intracellular survival & resistance to antimicrobial peptides(through activation of PrmA/PrmB system and production of protective membrane proteins)
- prg genes: extracellular survival & early steps in pathogenesis
- PrmA/PrmB: second two-component regulator that causes production of enzymes that modify LPS so that it no longer binds antimicrobial peptides
- PagC and other outer membrane proteins: allow Salmonella to resist some antimicrobial peptides
- Adhesins: adhesion to intestinal cells
- Enterotoxin: found in some strains; not necessary for virulence, or an important part of pathogenesis
- ## Flagella: allows movement through intestinal mucus; phase variation1) ingestion
2) exposure to body temperature triggers expression of genes
encoding invasive factors
3) Sip is transferred to host cell membrane
4) membrane ruffling
5) enters M cells & enterocytes via macropinocytosis
6) replicate in endosomes
7) released into lamina propria
8) phagocytosed by macrophages; live inside of macrophages
9) strong inflammatory response
10) can disseminate if immunocompromised
———————– - 12-48 hour incubation time
- fever and diarrhea
- septicemia and death in AIDS patients
- ## osteomyelitis and septicemia in sickle cell patients
- stool cultures
Salmonella typhi
Enterobacteriaceae
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Diagnosis Treatment and Prevention
- reservoir: human carriers (often with gallstones)
- transmission: fecal-oral contamination
- ## India subcontinent, Central & South America, Asia, Africa
- same virulence factors as non-typhoid Salmonella
- ## polysaccharide capsule containing Vi antigen1) similar to non-typhoid Salmonella, except it disseminates quickly once it reaches the lamina propria
2) moves through the blood and/or lymph to reticuloendothelial tissue (liver, spleen, bone marrow)
3) multiplies in those tissues
4) suddenly emerge 1-2 weeks later in the blood and bile
———————–
typhoid fever
initial symptoms: - low grade fever
- constipation
after 1-2 weeks: - septic shock
- high fever
- diarrhea
- hemorrhaging and perforation of the intestine, which can lead to peritonitis
- abdominal rose spots
- ## 10-20% mortality w/o treatment
- ## blood cultures
- Ciprofloxacin
- Ceftriaxone
Shigella spp.
Enterobacteriaceae
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases
- human reservoir
- fecal-oral
- ingestion of contaminated food or water
- extremely virulent
- ## person-to-person transmission
- resistant to gastric acid
- LPS: endotoxin
- Mxi-Spa proteins (translocon): needle of type III secretion system (TTSS)
- Ipa: transferred to host cell surface; induces membrane ruffling
- IcsA: causes reorganization of host cell cytoskeleton, allowing for motility
- IcsB: allows escape from vesicles when moving between adjacent colonocytes
- Shiga toxin: inactivates 60S ribosomal subunit, causing inhibition of protein synthesis; found in S. dysenteriae
- ## genes are plasmid-encoded1) ingestion
2) exposure to body temperature triggers expression of genes
encoding invasive factors
3) Ipa is transferred to host cell membrane
4) membrane ruffling
5) enters M cells via macropinocytosis
6) exit basal surface of M cells
7) use Ipas to invade basal surface of colonocytes
8) escape from endosome and multiply in the cytoplasm
9) use IcsA to move in cytoplasm
10) move directly between colonocytes via vesicles; IcsB is required for escape from vesicles
11) induce inflammation through interactions with macrophages and attracting neutrophils
12) GI symptoms and fever caused by colonic inflammation and sometimes Shiga toxin - ## restricted to epitheliumdiarrhea/dysentery with fecal leukocytes and fever
16-72 hour incubation time
Yersinia enterocolitica
Enterobacteriaceae
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases
Gram- enteric rod
- fecal-oral, or ingestion of contaminated food or water
- Yersinia outer proteins (YOPs): resist phagocytosis
- invasin: binds 1 integrin on M cells; bacterium is then pulled into host cell by zipper mechanism
- LPS: causes fever
- heat-stable enterotoxin: increases intestinal cGMP
- 1) invasin is made
2) ingestion
3) invasion of M cells
4) released into underlying subepithelial tissue of Peyer’s patches
5) spread to mesenteric lymph nodes - fever & diarrhea
- 72 hour incubation time
Yersinia pestis
Enterobacteriaceae
Morphology Transmission and Reservoir Virulence Factors Diseases Treatment and Prevention
Gram- enteric rod
safety pin morphology ----------------------- - rodent reservoir - flea vector - contagious - SW US ----------------------- - plasminogen activator - causes fleas to regurgitate it - Yersinia outer protein (YOP): inhibits phagocytosis & lymphocyte proliferation - LPS: endotoxic - polypeptide capsule ----------------------- acute febrile lymphadenitis (bubonic plague) - most common form - fevers, chills, weakness, headache, pain and swelling in lymph nodes pneumonic - 2-4 day incubation - pneumonia w/ bloody sputum - 50% mortality septicemic - bacteremia after escape from lymph nodes ----------------------- - Streptomycin or Gentamicin - Doxycycline or ciprofloxacin for PEP - contact isolation - droplet precautions for 72 hours after starting antibiotics
Klebsiella pneumoniae
Enterobacteriaceae
Morphology Transmission and Reservoir Virulence Factors Diseases Treatment and Prevention
- human reservoir (lower GI tract, skin colonization)
- ## contact
- mucoid polysaccharide capsule: resistant to phagocytosis
- adept at acquiring antibiotic resistance genes
- chromosomally- encoded β-lactamase: inactivates penicillin
- extended spectrum beta lactamase (ESBL): resistance to all β-lactams except
carbapenems - carbapenemase:
resistant to all -lactams including carbapenems
———————– - bacteremia
- nosocomial pneumonia
- ## UTI
- Ampicillin + Sulbactam
- Amoxycillin + Clavulanate
- 1st and 2nd generation cephalosporins
- Nitrofurantoin
- contact precautions when multi-drug resistant
Proteus mirabilis
Enterobacteriaceae
Morphology
Diseases
Treatment and Prevention
Gram- enteric rod ----------------------- catheter-associated UTI ----------------------- - Aminopenicillins +/- B-lactamase inhibitors
Enterobacter cloacae
Enterobacteriaceae
Morphology
Diseases
Treatment and Prevention
Gram- enteric rod ----------------------- hospital-acquired pneumonia ----------------------- - Nitrofurantoin
Vibrio cholerae
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Diagnosis Treatment and Prevention
Gram- enteric rod
- reservoir: estuary waters and asymptomatically colonized people
- ingestion of contaminated food or water
- stool contains a very high number of infectious bacteria
- ## vomit can also contain infectious bacteria
- toxin-coregulated pilus (TCP): required for colonization of small intestine epithelium; receptor for phage
- cholera toxin: causes ADP-ribosylation of Gs, causing activation of adenylate cyclase and accumulation of intestinal cAMP
- accessory enterotoxins
- biofilm production: protects bacteria from acidic environment of the stomach
- flagella: involved in movement through intestinal mucus to reach epithelium
- CTXf phage carries genes that encode cholera toxin and accessory enterotoxins
- TCP and cholera toxin are coordinately expressed
- ## TcpP and ToxR regulatory proteins transcription of ToxT ToxT protein transcription of cholera toxin (from ctxAB gene) and TCP (from tcp operon)1) ingested
2) colonizes small intestine
3) produces cholera toxin
———————–
cholera - incubation period of several hours to several days
- moderate to severe diarrhea
- “rice water stool”
- vomiting
- severe dehydration
- ## cardiac problems, shock, death
- microscopy: comma-shaped and flagellated
- isolate on TCBS agar
- classify by Serotyping (O1 and O139 are associated with epidemic/ pandemic spread)
- ## no fecal leucocytes
- IV fluids in severe cases
- oral rehydration solution containing salts and glucose
- antibiotics to lessen disease severity and duration and limit spread
Campylobacter jejuni
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Treatment and Prevention
Gram- enteric
rod
curved
motile
microaerophilic
- reservoir: animals, including pets
- ingestion of contaminated food (poultry) or water
- ## contact with sick pets
- adhesins
- LPS
- enterotoxin: causes ADP-ribosylation of Gs, resulting in activation of adenylate cyclase and accumulation of intestinal cAMP; not required for pathogenesis
- ## gangliosides sugars mimic neuronal tissue and are associated with Guillain-Barre syndromeinvades lower small intestine or upper large intestine and induces inflammation
———————– - 3-5 day incubation
- cramps, diarrhea (sometimes with fecal leucocytes), fever
- ## Guillain-Barre syndrome
- macrolides
- tetracyclines
Helicobacter pylori
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Diagnosis Treatment and Prevention
Gram- enteric rod
curved
motile
microaerophilic
grows best at 37C
- human reservoir
- fecal-oral
- oral-oral
- urease: produces ammonia and bicarbonate from urea; raises local pH
- flagella: used to move into the mucus membrane where pH is higher
- LPS: weak endotoxin
- vacuolating cytotoxin (VacA): damages stomach epithelial cells
- CagA: induces inflammation
- type IV secretion system
- CagA and secretion system are on cag pathogenicity island
- ingested
- protects itself from stomach acid using urease and by moving into mucus layer
- induces inflammation via VacA, CagA, and ammonia (produced by urease)
- mild GI disease
- chronic gastritis
- duodenal or gastric ulcers
- gastric cancer or gastric lymphoma
- endoscopy
- breath tests using radioactive urea
- serologic tests
- macrolides
- metronidazole
Pseudomonas aeruginosa
Morphology Transmission and Reservoir Virulence Factors Diseases Treatment and Prevention
Gram- enteric rod
aerobic
motile
blue-green pigment ----------------------- - contaminated water - can’t penetrate the epithelium, so mainly causes diseases through wounds, surgical incisions, and burns - infects people with CF ----------------------- - polysaccharide capsule: anti-phagocytic; important for making biofilms - protease and elastase: cause tissue damage - exotoxin A: ADP-ribosylates EF-2 causing inhibition of host cell protein synthesis; causes necrosis - leucocidin: inhibits/kills WBCs - phospholipase C: hemolysin, affects WBCs - endotoxin: promotes shock; relatively weak compared to other endotoxins - pili: adhesion - quorum sensing system - PAI-1 LASR transcription of Exotoxin A and PAI-2 - PAI2 RhIR transcription of additional virulence factors ----------------------- - hospital-acquired pneumonia - CF infections - burn infections - catheter-associated UTI - IV line-associated bacteremia - disseminated infection can lead to cellulitis - high mortality rate ----------------------- “Get MIC and PD to TACCL PA” - Gentamicin - Meropenem - Imipenem - Ciprofloxacin - Polymyxins - Doripenem - Tobramycin - Amikacin - Cefepime - Ceftazidime - Levofloxacin - Piperacillin - Aztreonam
Bacteroides fragilis
Morphology Transmission and Reservoir Virulence Factors Diseases Treatment and Prevention
Gram- enteric rod
anaerobic ----------------------- - found in colon -endogenous infection ----------------------- - capsule - enterotoxin (some species) - proteases & enzymes - LPS (not endotoxic) ----------------------- intra-abdominal infections (peritonitis followed by abscess formation) & bacteremia ----------------------- These Many Medications Can Confidently Cover Bacteroides 1) Tigecycline 2) Metronidazole 3) Moxifloxacin 4) Clindamycin 5) Cefoxitin 6) Carbapenems 7) B-lactams + B-lactamase inhibitors
Porphyromonas gingivalis
Morphology
Transmission and Reservoir
Virulence Factors
Diseases
Gram- rod
anaerobic
bile-sensitive ----------------------- - found in mouth - endogenous infection ----------------------- - endotoxic LPS - proteases and other enzymes ----------------------- respiratory tract infections
Prevotella melaninogenica
Morphology
Transmission and Reservoir
Virulence Factors
Diseases
Gram- rod
anaerobic
bile-sensitive ----------------------- - found in mouth - endogenous infection ----------------------- - capsule - endotoxic LPS - proteases and other enzymes ----------------------- respiratory tract infections
Prevotella bivia
Morphology
Transmission and Reservoir
Virulence Factors
Diseases
Gram- rod
anaerobic
bile-sensitive ----------------------- - found in female genital tract - endogenous infection ----------------------- - endotoxic LPS - proteases and other enzymes ----------------------- pelvic inflammatory disease; infertility
Haemophilus influenzae
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Diagnosis Treatment and Prevention
Gram- rod (pleomorphic coccobacilli) ----------------------- - human reservoir - inhalation of droplets ----------------------- - PRP capsule in typeable strains; no capsule in non-typeable strains (capsule not required for virulence) - endotoxic LOS - IgA protease - adhesins - ability to obtain iron from heme and transferrin ----------------------- 1) transmission 2) absence of protective antibody 3) colonization 4) viral infection or humoral deficiency 5) infection ----------------------- non-typeable - otitis media - sinusitis - lower respiratory tract infection in adults type b - epiglottitis - pneumonia - meningitis (particularly neonatal) - bacteremia ----------------------- - requires lysed RBCs for growth ----------------------- - Aminopenicillins +/- B-lactamase inhibitors - 2nd generation cephalosporins - macrolides - tetracyclines
Legionella pneumophila
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases Diagnosis Treatment and Prevention
Gram- rod ----------------------- - bodies of water - grows as a biofilm in water sources, since it can survive chlorination - normally lives in protazoa - inhalation - not transmitted between people ----------------------- - prevents phago-lysosome fusion by remodeling phagosome to look like RER - type IV secretion system (dot/icm genes): may allow rapid secretion of effector molecules to modulate phagosome and prevent fusion with lysosomes - two mutually exclusive sets of genes for virulence: those involved in replication phase and those involved in transmission - flagellum - multiple fimbriae ----------------------- - lives in macrophages ----------------------- Legionnaires’ disease - pneumonia - cough, fever, diarrhea - 2-10 day incubation Pontiac fever - acute febrile illness without pneumonia ----------------------- - LPS antigen in urine ----------------------- - tetracyclines - macrolides - fluoroquinolones
Bordetella pertussis
Morphology Transmission and Reservoir Virulence Factors Pathogenesis Diseases
Gram- rod
- highly communicable
- ## reservoir: asymptomatic adults
- pertussis toxin: ADP-ribosylates Gi protein, resulting in activation of mammalian adenylate cyclase and increasing cAMP levels
- bacterial adenylate cyclase
- tracheal cytotoxin: specifically kills ciliated cells and induces local damage
- heat-labile (dermonecrotic) toxin: local damage
- regulated by two component regulatory system
- bvgS: surface receptor
- ## bvgA: transcriptional regulator
- accumulation of mucus, cells, and bacteria in the airways
- mucociliary elevator is impaired
- ## cough is easily triggered because of sensitization of cough receptors by a toxin produced by the bacteriawhooping cough
- intense coughing that can lead to hemorrhage or vomiting
complications - secondary infections including pneumonia
- CNS abnormalities
- can be life-threatening
Francisella tularensis
Morphology Transmission and Reservoir Virulence Factors Diseases Treatment and Prevention
Gram- rod ----------------------- reservoir: - various animals infectious material: - tick saliva or feces - contaminated animal products - water - dust - hay transmission - tick bite - inoculation into wound - contact - inhalation - ingestion - not transmissible between people very virulent found in Martha’s vineyard ----------------------- - capsule - FPI pathogenicity island: cluster of genes that are responsible for intracellular survival ----------------------- tularemia - 3-5 day incubation - fever, chills, headache, malaise, anorexia, fatigue - ulceroglandular (lesion + lymphadenopathy) - oculoglandular - pharyngeal - glandular - pneumonic - typhoidal: disseminated infection that does not fall into other categories - 4% fatality ----------------------- - Streptomycin or Gentamicin - Doxycycline or Ciprofloxacin for PEP - alert microbiology lab, b/c very virulent
Acinetobacter spp.
Morphology
Transmission and Reservoir
Virulence Factors
Diseases
Gram- rod ----------------------- - soil (e.g. Afghanistan) - contact, wounds ----------------------- - endotoxin - resistant to desiccation - readily acquires antibiotic resistance genes ----------------------- hospital-acquired pneumonia (e.g. ventilator-associated)
Enterobacteriaceae general
- Gram negative
- Faculative anaerobe: oxidase negative
- isolated from feces, urine, blood and CSF
- Cultivated on media containing bile (MacConkey)
- Motile or non motile
speciation relies on lactose utilization