Mechanisms of Antibiotic Resistance Flashcards
Penicillin cannot pass through the _______, so all Gram-negative bacteria are resistant to penicillins.
porin channels
Efflux pumps can be found in _______ or _______.
Gram-positive; Gram-negative
Efflux pumps can be ____________.
specific (such as the pump for tetracycline) or general
How do beta-lactams work?
They irreversibly bind to penicillin-binding proteins; PBPs are the two enzymes that are responsible for stage 3 cell-wall synthesis, transpeptidase and transglycosylase.
There are three ways that bacteria become resistant to beta-lactams: _________.
they alter their PBPs, decrease entry through porins, or degrade the drug
Genes for beta-lactamases are found ___________.
in chromosomes and plasmids; in Gram-positive and Gram-negative bacteria
Most beta-lactamases can be inhibited by _____________.
beta-lactamase inhibitors
List the characteristics of penicillinases.
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.
All Staphylococcus are resistant to ___________ because of the ________ gene.
penicillin, amoxicillin, and ampicillin; bla
E. coli occasionally becomes resistant to ________ with its TEM-1 plasmid.
ampicillin
K. pneumoniae is resistant to ampicillin because of a __________ gene.
chromosomal (SHV-1)
MSSAs have bla, so they will not be killed by _________, but they can be killed by drugs that are not susceptible to beta-lactamases.
penicillin, amoxicillin, or ampicillin
ESBLs are ____________.
extended-spectrum beta-lactamases, enzymes that can degrade penicillins and cephalosporins
ESBLs are transmitted __________.
on plasmids
ESBLs are still sensitive to __________.
some beta-lactamase inhibitors
ESBL-possessing bacteria can be killed with _______.
carbapenems
ampC is located in _________.
chromosomes of Gram-negative rods
Where is ampC found? What are some of its characteristics?
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
The production of ampC is induced by _________.
ampicillin and cefazolin; it can be constitutively activated by a random mutation
Carbapenemases degrade ___________.
penicillins, cephalosporins, and carbapenems (i.e., all beta-lactams)
Carbapenemases are not ___________.
susceptible to beta-lactamase inhibitors
Carbapenems are found on ___________.
plasmids (frequently taken up by E. coli and Klebsiella)
The two carbapenemases known are _________.
KPC and NDM-1
Staphylococcus aureus becomes MRSA when it acquires __________.
a plasmid encoding mecA (PBP2a), a penicillin-binding protein
Because it is a unique PBP, mecA causes S. aureus to be resistant to ___________.
all beta-lactams
Similar to MRSA, Streptococcus pneumoniae and Neisseria gonorrhoeae become resistant to penicllins by ________.
altering its PBP, creating a new target
Streptococcus have never been shown to ___________.
express beta-lactamases–they are all resistant by altering PBP structure
What does vancomycin bind to?
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
There are only two drugs that treat Clostridium difficile: ___________.
metronidazole and vancomycin
How does Enterococcus become resistant to vancomycin?
It gets a plasmid that expresses an enzyme that converts D-alanine D-alanine to D-alanine D-lactate
By what two ways do bacteria become resistant to macrolides?
Through the msr gene (which pumps out macrolides) and the erm gene (which modifies the 23S subunit of the 50S subunit of bacterial rRNA
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.
clindamycin
If a D-test is positive, this indicates that the Staph is erm (_______); do not administer clindamycin, because you might _________.
inducible; select for mutants that are constitutive erm
The majority of fluoroquinolone resistance occurs by ____________.
point mutations (in the quinolone-resistance determining region “QRDR”)
Almost all resistance to aminoglycosides occurs by ______________.
drug modification
Vancomycin cannot pass through ____________.
the outer membrane of Gram-negative organisms
There are three narrow beta-lactamases. Which two are plasmid-mediated?
bla and TEM-1 (SHV is chromosomal)
How has MRSA become resistant?
It acquired mecA, a PBP2a gene that cannot be targeted by any beta-lactam except cefepime and ceftaroline
How is vancomycin resistance carried?
On plasmids encoding vanA and vanB
Most E. coli and Klebsiella contain ______, which is why they’re not susceptible to _________.
a narrow-spectrum beta-lactamase; penicillin
