Mechanisms of Antibiotic Resistance

Question 1

Penicillin cannot pass through the _______, so all Gram-negative bacteria are resistant to penicillins.

Answer 1

porin channels

Question 2

Efflux pumps can be found in _______ or _______.

Answer 2

Gram-positive; Gram-negative

Question 3

Efflux pumps can be ____________.

Answer 3

specific (such as the pump for tetracycline) or general

Question 4

How do beta-lactams work?

Answer 4

They irreversibly bind to penicillin-binding proteins; PBPs are the two enzymes that are responsible for stage 3 cell-wall synthesis, transpeptidase and transglycosylase.

Question 5

There are three ways that bacteria become resistant to beta-lactams: _________.

Answer 5

they alter their PBPs, decrease entry through porins, or degrade the drug

Question 6

Genes for beta-lactamases are found ___________.

Answer 6

in chromosomes and plasmids; in Gram-positive and Gram-negative bacteria

Question 7

Most beta-lactamases can be inhibited by _____________.

Answer 7

beta-lactamase inhibitors

Question 8

List the characteristics of penicillinases.

Answer 8

They (1) only break down penicillins; (2) are not active against cephalosporins; (3) can be located in chromosomes or on transferable elements; and (4) are susceptible to beta-lactamase inhibitors.

Question 9

All Staphylococcus are resistant to ___________ because of the ________ gene.

Answer 9

penicillin, amoxicillin, and ampicillin; bla

Question 10

E. coli occasionally becomes resistant to ________ with its TEM-1 plasmid.

Answer 10

ampicillin

Question 11

K. pneumoniae is resistant to ampicillin because of a __________ gene.

Answer 11

chromosomal (SHV-1)

Question 12

MSSAs have bla, so they will not be killed by _________, but they can be killed by drugs that are not susceptible to beta-lactamases.

Answer 12

penicillin, amoxicillin, or ampicillin

Question 13

ESBLs are ____________.

Answer 13

extended-spectrum beta-lactamases, enzymes that can degrade penicillins and cephalosporins

Question 14

ESBLs are transmitted __________.

Answer 14

on plasmids

Question 15

ESBLs are still sensitive to __________.

Answer 15

some beta-lactamase inhibitors

Question 16

ESBL-possessing bacteria can be killed with _______.

Answer 16

carbapenems

Question 17

ampC is located in _________.

Answer 17

chromosomes of Gram-negative rods

Question 18

Where is ampC found? What are some of its characteristics?

Answer 18

In Gram-negative rods (Pseudomonas and Enterobacter, to be specific); it can degrade penicillins and cephalosporins; it is not susceptible to beta-lactamase inhibitors, but the bacteria remain susceptible to carbapenems; is inducible

Question 19

The production of ampC is induced by _________.

Answer 19

ampicillin and cefazolin; it can be constitutively activated by a random mutation

Question 20

Carbapenemases degrade ___________.

Answer 20

penicillins, cephalosporins, and carbapenems (i.e., all beta-lactams)

Question 21

Carbapenemases are not ___________.

Answer 21

susceptible to beta-lactamase inhibitors

Question 22

Carbapenems are found on ___________.

Answer 22

plasmids (frequently taken up by E. coli and Klebsiella)

Question 23

The two carbapenemases known are _________.

Answer 23

KPC and NDM-1

Question 24

Staphylococcus aureus becomes MRSA when it acquires __________.

Answer 24

a plasmid encoding mecA (PBP2a), a penicillin-binding protein

Question 25

Because it is a unique PBP, mecA causes S. aureus to be resistant to ___________.

Answer 25

all beta-lactams

Question 26

Similar to MRSA, Streptococcus pneumoniae and Neisseria gonorrhoeae become resistant to penicllins by ________.

Answer 26

altering its PBP, creating a new target

Question 27

Streptococcus have never been shown to ___________.

Answer 27

express beta-lactamases–they are all resistant by altering PBP structure

Question 28

What does vancomycin bind to?

Answer 28

D-alanine dimers on the end of the peptide that hangs off of MurNAc; it is so big, comparatively, that it prevents peptidoglycan from cross-linking

Question 29

There are only two drugs that treat Clostridium difficile: ___________.

Answer 29

metronidazole and vancomycin

Question 30

How does Enterococcus become resistant to vancomycin?

Answer 30

It gets a plasmid that expresses an enzyme that converts D-alanine D-alanine to D-alanine D-lactate

Question 31

By what two ways do bacteria become resistant to macrolides?

Answer 31

Through the msr gene (which pumps out macrolides) and the erm gene (which modifies the 23S subunit of the 50S subunit of bacterial rRNA

Question 32

erm (methylation of the 50S subunit) is inducible or constitutive; when it is induced by macrolides or constitutively turned on, however, it leads to resistance to ________, as well.

Answer 32

clindamycin

Question 33

If a D-test is positive, this indicates that the Staph is erm (_______); do not administer clindamycin, because you might _________.

Answer 33

inducible; select for mutants that are constitutive erm

Question 34

The majority of fluoroquinolone resistance occurs by ____________.

Answer 34

point mutations (in the quinolone-resistance determining region “QRDR”)

Question 35

Almost all resistance to aminoglycosides occurs by ______________.

Answer 35

drug modification

Question 36

Vancomycin cannot pass through ____________.

Answer 36

the outer membrane of Gram-negative organisms

Question 37

There are three narrow beta-lactamases. Which two are plasmid-mediated?

Answer 37

bla and TEM-1 (SHV is chromosomal)

Question 38

How has MRSA become resistant?

Answer 38

It acquired mecA, a PBP2a gene that cannot be targeted by any beta-lactam except cefepime and ceftaroline

Question 39

How is vancomycin resistance carried?

Answer 39

On plasmids encoding vanA and vanB

Question 40

Most E. coli and Klebsiella contain ______, which is why they’re not susceptible to _________.

Answer 40

a narrow-spectrum beta-lactamase; penicillin