M11a: Fungal Infections and Antifungal Drugs

Question 1

What are fungi and how does it differentiate from bacteria?

– Fungi are (eukaryotic / prokaryotic) organisms

– Most fungi are obligate or facultative (aerobes / anaerobes)

– Fungi are _, secreting enzymes that _ a wide variety of organic substrates into soluble nutrients which are then passively _ or taken into the cell by _ transport

– Fungi reproduce (sexually / asexually)

– Fungi are (motile / nonmotile): they are spread by _, _, and _

Answer 1

eukaryotic

aerobes

chemotrophic
degrade
absorbed
active

sexually

nonmotile
wind, water and contact

Question 2

What are fungi and how does it differentiate from bacteria?

– Toxins (contribute / do not contribute) to the pathogenesis of fungal infections. Although poisoning from preformed fungal toxins (_) by ingestion can occur, these fungi do not actually infect

– Most fungi (_ is an exception) remain (stained / unstained) with Gram stain

– All fungi stain with _ (fungi appear a brilliant white under the fluorescent microscope)

– All fungal cell walls are stained by _ stains and (while the fungus remains viable) the _ reagent will stain the polysaccharide in the cell wall

– Fungi can produce _ to enhance their survival. These can be _, are _ to adverse conditions, and can _ when conditions for growth are favorable.

Answer 2

do not contribute
mycotoxin

Candida
unstained

calcofluor

silver
periodic acid-Schiff (PAS)

spores
dispersed
resistant
germinate

Question 3

Fungi:

(Eukaryotic / Prokaryotic)

Nuclear membrane (y / n)

Chromosomes (1 / >1)

Mitochondria (y / n)

Endoplasmic reticulum (y / n)

Ribosome (70S / 80S)

Sterols (y / n)

Cell wall made up of _, _, _, & _

(Homotrophic / Heterotrophic)

(Mostly aerobes / Obligate aerobes/anaerobes & facultative anaerobes)

Photosynthesis (y / n)

Dimorphism (y / n)

Answer 3

Eukaryotic

y

> 1

y

y

80S

y

glucans, mannoproteins (mannans), chitin, chitosan

Heterotrophic

Mostly aerobes

n

y

Question 4

Bacteria:

(Eukaryotic / Prokaryotic)

Nuclear membrane (y / n)

Chromosomes (1 / >1)

Mitochondria (y / n)

Endoplasmic reticulum (y / n)

Ribosome (70S / 80S)

Sterols (y / n)

Cell wall made up of _, _, & _

(Homotrophic / Heterotrophic)

(Mostly aerobes / Obligate aerobes/anaerobes & facultative anaerobes)

Dimorphism (y / n)

Answer 4

Prokaryotic

n

1

n

n

70S

n

murein, teichoic acids (gram positives), peptidoglycans

Heterotrophic

Obligate aerobes/anaerobes & facultative anaerobes

n

Question 5

Constituents of the fungal cell wall:

– Mannan: a _ based polymer found on the surface and in the structural matrix of the fungal cell coat, where it can be covalently attached to _

– Glucans: _ polymers, some of which form _ that increase the strength of the fungal cell coat

– Chitin: not found in all fungi; composed of long polymers of _

Answer 5

mannose
proteins

glucosyl
fibrils

N-acetylglucosamine

Question 6

Growth forms of fungi:
Molds:

– Also known as _ fungi

– Multicellular forms composed of tubular structures called _

– A _ is the basic element of filamentous fungi with a _, tubular structure, 2-10 µm in width

– Grow by _ and _

Answer 6

filamentous

hyphae

hypha
branched

branching
longitudinal extension

Question 7

Growth forms of fungi:
Molds:

– Hyphae may be _ (_ dividing the hyphae into discrete cellular units) or _ (resulting in a single continuous filamentous fungal cell)

– A web of intertwined hyphae is called a _; colonies typically appear fuzzy

– Are speciated by colonial morphology and color, and microscopic appearance

– Include (4)

Answer 7

septate
septa
non-septate

mycelium

Aspergillus spp.
Mucor
Penicillium marneffei
Fusarium, Scedosporium

Question 8

Growth forms of fungi:
Yeasts:

– (Unicellular / Multicellular) forms

– Are _ to _ in shape and 3-10 µm in diameter

– Form _, _ colonies, that resemble bacterial colonies on agar (but are typically (smaller / larger) and somewhat more _)

– Reproduce by _

Answer 8

Unicellular

round to oval

smooth, flat
larger
opaque

budding

Question 9

Growth forms of fungi:
Yeasts:

– May produce _; several elongated yeasts cells chained together and resembling true _. These are _ that fail to detach and become elongated

– Are speciated by _ tests

– Include (2)

Answer 9

pseudohyphae (pseudomycelium)
hyphae
buds

biochemical

Candida spp.
Cryptococcus neoformans

Question 10

Growth forms of fungi:
Dimorphic fungi:

– Fungal species that can grow either the _ or _ form depending on the environmental conditions

– Grow as yeast-like forms (hyphae / budding) in the (parasitic / saprophytic) stage

– Grow as molds (hyphae / budding) in the (parasitic / saprophytic) stage

– Include (4)

Answer 10

yeast or mycelium

budding
parasitic

hyphae
saprophytic

Histoplasma capsulatum
Blastomyces dermatitidis
Coccidioides immitis
Sporothrix schenckii

Question 11

General aspects of fungal disease:

– _ mycoses are the most frequent fungal infections worldwide

– Patients who develop _ mycoses have serious underlying diseases and compromised host defenses. These are increasing in recent decades due to the increasing numbers of hosts with _ and the high frequency of invasive and aggressive _

– Mechanical, humoral and cellular factors provide non-specific _ to most fungi

– _ is the most important resistance factor; followed by _

Answer 11

Cutaneous

opportunistic
immune defects
medical therapies

resistance

Phagocytosis by neutrophilic granulocytes and macrophages
cellular immunity

Question 12

General aspects of fungal disease:
Fungal allergies:

– Spores of fungi contain potent _ and continuously enter the _. Susceptible individuals may manifest strong _ reactions.

– It may present as _, _, or _, depending on the site of deposition of the allergen.

– Some are _ diseases, such as “farmer’s lung” and “woodworker’s lung”.

Answer 12

allergens
respiratory tract
hypersensitivity

allergic rhinitis
bronchial asthma
allergic alveolitis

occupational

Question 13

General aspects of fungal disease:
Fungal toxicoses:

– Some fungi produce _, which are ingested with the food on which the fungi have been growing. The effects of them do not depend on fungal _ or _.

– The best known are _, produced by _.

Answer 13

mycotoxins
infection or viability

aflatoxins
Aspergillus spp

Question 14

Candida (yeast):

Candida spp. are the most important fungi to infect humans.

Candidiasis is the most common _ mycoses.

Several Candida species can cause disease in humans, but _ has historically been the most frequent species to infect humans.

_ Candida species (such as C. glabrata), have become more common isolates in hospitalized patients.

This is because C. glabrata is less susceptible than C. albicans to an antifungal drug called _, which is widely used as prophylaxis to prevent fungal infections.

This drug will decrease colonization of _ and its ecologic niche replaced by _.

Answer 14

systemic

Candida albicans

Non-albicans

fluconazole

C. albicans
C. glabrata

Question 15

Candida (yeast):

Candida is a normal inhabitant of the (4)

The normal bacterial flora in these environments, intact cellular immunity, granulocytes and the integrity of normal mucous membranes prevent its invasion.

Conditions that alter these normal controls are risk factors for locally invasive or disseminated disease:

• _ that destroy the normal bacterial flora of the GI tract and vagina
• _ and _ that impair cellular immunity and induce neutropenia
• _ that cause mucosal injury and ulceration of the GI tract.

_, which causes a breach in the normal GI tract leading to spillage of organisms into the peritoneal cavity, is another risk factor.

Most of these conditions are _ and invasive candidiasis is usually a disease of the _.

Answer 15

mouth
skin
gastrointestinal tract
vagina

• antibiotics
• steroid and anti-metabolites
• chemotherapeutic agents

Gastrointestinal surgery

iatrogenic
severely ill, hospitalized patient

Question 16

Candida (yeast):

Cell-mediated immune responses, especially CD4 cells, are important in controlling _ candidiasis, and neutrophils are probably crucial for resistance to _ candidiasis.

Candida can cause a wide spectrum of disease, from superficial invasion of the (4) to _ and _ infection.

Answer 16

mucocutaneous
systemic

mouth (“thrush”), esophagus, vagina and skin (“diaper rash”)
abscesses
bloodstream

Question 17

Candida (yeast):
Cutaneous and mucosal candidiasis:

– Thrush occurs in the (4). Risk factors include (4)

– Vulvovaginitis is often preceded by (3) that alter the normal vaginal flora, local acidity or secretions

– Cutaneous candidiasis occurs mostly in _, _ parts of the body; it is most common in _ and _ individuals

Answer 17

tongue, lips, gums or palates
AIDS, use of corticosteroids or antibiotics, high levels of glucose, and cellular immunodeficiency

diabetes, pregnancy, or antibacterial drugs

moist, warm
obese and diabetic

Question 18

Candida (yeast):
Systemic candidiasis:

– Occurs when Candida enters the _ and the phagocytic host defenses are inadequate to control its _ and _

– In most patients with normal host defenses, candidemia is _; however, in patients with compromised phagocytic defenses occult lesions can develop anywhere, especially in the (3)

Answer 18

bloodstream
growth and dissemination

transient
eye, heart and meninges

Question 19

Candida (yeast):

The treatment of candidiasis depends on the disease that it is causing.

Thrush and other mucocutaneous candidiasis are usually treated with topical _ or oral or topical _.

In cases of systemic infections, (3) can be used.

Answer 19

nystatin
azoles

azoles
echinocandins
amphotericin B

Question 20

Cryptococcus neoformans (yeast):

Cryptococcus neoformans and C. gattii are _ yeasts with (small / large) polysaccharide capsules.

C. neoformans occurs _, C. gattii is (more / less) common and typically associated with _.

Both species cause _. Theses yeasts are _.

Yeast cells or spores are inhaled and from the lungs typically migrate to the _, but can infect many other organs.

C. neoformans infection can occur in normal hosts; however, it is more commonly seen in patients with (4) conditions.

C. gattii infection is (more / less) common and usually associated with normal hosts.

Answer 20

encapsulated
large

worldwide in nature
less
trees in tropical areas

cryptococcosis
neurotropic

central nervous system

AIDS, hematologic malignancies, organ transplants, and other immunosuppressive

less

Question 21

Cryptococcus neoformans (yeast):
Pathogenicity:

– The _ of C. neoformans is an important defense against phagocytosis of the fungus

– The fungus produces _ which may serve as a protection against oxidative stress

Answer 21

polysaccharide capsule

melanin

Question 22

Cryptococcus neoformans (yeast):
Manifestations of the infection:

– Most patients with cryptococcosis have an underlying _

– The fungus enters the body via the _. Infection occurs after _ of yeast cells, which in nature are dry, minimally encapsulated and easily _

– From the primary pulmonary foci it may spread hematogenously to other organs, especially to the _, causing _

– Other manifestations are _ and _ infection

– Human _ (especially CD4+ cells) inhibit growth of C. neoformans by direct contact. _ deficiencies (such as AIDS or induced medically by organ transplantation) are major risk factors for cryptococcal meningitis

Answer 22

immunocompromised state

respiratory tract
inhalation
aerosolized

central nervous system
meningoencephalitis

skin and bloodstream

lymphocytes
T lymphocyte

Question 23

Cryptococcus neoformans (yeast):
Microbiologic diagnosis:

– The simple method of mixing together _ with _ (especially cerebrospinal fluid) rapidly identifies the encapsulated yeasts

– _ tests for the detection of cryptococcal polysaccharide antigens in blood and cerebrospinal fluid are also rapid and very useful. The _ test for cryptococcal antigen is positive in 90% of patients with cryptococcal meningitis

– The organism can be cultured on _ media

Answer 23

India Ink with body fluids

Serologic
latex slide agglutination

most

Question 24

Cryptococcus neoformans (yeast):
Treatment:

– _ plus 5-flucytosine, followed by _

– A subset of AIDS patients treated with highly antiretroviral therapy and organ transplant recipients who have their immunosuppression decreased develop _, which exacerbates their illness

Answer 24

Amphotericin
fluconazole

immune reconstitution syndrome (IRS)

Question 25

Dermatophytes (mold):

These fungi only infect the _, using _as a nutritional source.

These fungi are (yeasts / molds). Most are (able / unable) to grow at 37oC or in the presence of serum.

These cutaneous fungal infections are extremely (common / rare) and include diseases such as “ring worm” and “athlete’s foot”. They occur all over the world but may be more common in _ areas.

Answer 25

superficial keratin layer of the skin
keratin

molds
unable

common
tropical

Question 26

Dermatophytes (mold):

There are three sources of infection (3)

Answer 26

1. Zoophilic dermatophytes
2. Geophilic dermatophytes
3. Anthropophilic dermatophytes

Question 27

Dermatophytes (mold):

There are three sources of infection:

1. Zoophilic dermatophytes

– These are primarily (human / animal) pathogens that sometimes cause (human / animal) infection

– _ may cause _ (“ring worm”), which frequently occurs in children. It may also occur on the scalp (_)

2. Geophilic dermatophytes

– These dermatophytes originate in the _

3. Anthropophilic dermatophytes

– These are the (most / least) common dermatophyte infections and are natural pathogens of humans

– _ causes _ (“athlete’s foot”) – the main symptom is itching in the interdigital spaces of the feet

– It may also cause _ (“jock itch”)

– _ (fungal infections of the nails) are usually due to anthropophilic fungi

Answer 27

animal
human

Microsporum canis
tinea corporis
tinea capitis

soil

most

Trichophyton rubrum
tinea pedis

tinea cruris

Onychomycosis

Question 28

Dermatophytes (mold):
Diagnosis of the dermatophytes:

– Scrapings of the skin or clippings of the nails can be examined _ (using a potassium hydroxide solution or calcofluor white) and be _ (often using a medium such as Sabouraud’s agar)

– _ will fluoresce green when examined using a filtered ultraviolet light source (“Wood’s light”)

Answer 28

microscopically
cultured

Microsporum spp.

Question 29

Dermatophytes (mold):
Treatment of the dermatophytes:

– Topical therapy: especially the _

– Oral therapy: _ or the _

Answer 29

imidazoles

terbinafine
azoles

Question 30

Pneumocystis jiroveci:

– Previously known as _

– P. jiroveci was once thought to be a protozoan but molecular biologic studies have proved that it is a _

– Lacks _

– Most people are probably infected with P. jiroveci as children, but the natural history of the infection is not clear. What is well understood is that P. jiroveci produces a form of _ in individuals with T-cell impairment such as patients with human immunodeficiency virus (HIV) infection or solid-organ transplant recipients

– Of great importance is that PJP can be prevented by giving _ (Bactrim) to patients at risk

Answer 30

P. carinii

fungus

ergosterol

pneumonia (PJP)

trimethoprim/sulfamethoxazole