8.11-8.12

Question 1

antibiotic efficacy has been compromised by

Answer 1

bacterial resistance mechanisms that include mutations that alter the targets, drug destruction or efflux, and entering a transient dormant state.

Question 2

Antibiotics

Answer 2

antimicrobial agents produced by microorganisms, primarily certain bacteria and fungi. These agents are characterized by their ability to either kill or inhibit the growth of bacteria, and all target molecular processes in the cell that are essential to growth and survival.

Question 3

antibiotics spe- cifically target

Answer 3

enzymes that catalyze DNA replication, RNA synthesis, and protein synthesis

Question 4

quinolones

Answer 4

such as ciprofloxacin target DNA gyrase in gram-negative bac- teria and topoisomerase IV in gram-positive bacteria. Thus quinolones lead to cell death by interfering with DNA unwinding and replication

Question 5

antibiotics rifampin and actinomycin

Answer 5

prevent RNA synthesis by either blocking the RNA polymerase active site (rifampin) or blocking RNA elongation by binding to the major groove in DNA

Question 6

antibiotic puromycin

Answer 6

contains a region that mimics the 3′ end of a tRNA, and this structural mimicry results in specific binding of the anti- biotic to the A site in the 70S ribosome; this induces chain termination and effectively shuts down protein synthesis.

Question 7

Aminoglycoside antibiotics

Answer 7

(e.g., streptomycin) target 16S rRNA of 30S
ribosome, leading to error-filled proteins that inhibit growth

Question 8

Antibiotics That Target the Cell Membrane and Wall

Answer 8

– Daptomycin specifically binds to phosphatidylglycerol
residues of bacterial cytoplasmic membrane, leading
to pore formation, depolarization, and death
– Polymyxins are cyclic peptides whose long
hydrophobic tails target LPS layer, disrupting
membrane and causing leakage and death

Question 9

Antibiotics That Target the Cell Membrane and Wall

Answer 9

– targeting peptidoglycan synthesis
▪ β-lactams (penicillin, cephalosporin, derivatives)
interfere with transpeptidation (formation of cross-
links) between muramic acid residues
▪ Vancomycin binds to pentapeptide precursor and
prevents interbridge formation
▪ Bacitracin binds to bactoprenol and prevents new
peptidoglycan precursors from reaching site of
synthesis

Question 10

Antibiotic Resistance: Spontaneous Mutations and Antibiotic
Modification

Answer 10

– Resistance mechanisms genetically encoded in four classes:
modification of drug target, enzymatic inactivation, removal via
efflux pumps, metabolic bypasses (Figure 8.28)
– Random chromosomal mutations can lead to resistance
▪ e.g., Spontaneous mutants resistant to rifampin can be
obtained by exposing a large population and selection
– Resistance genes can exist on mobile genetic elements and be
transferred by horizontal gene flow
▪ Many mobile resistance genes encode enzymes that
inactivate antibiotic (e.g., β-lactamase cleaves a ring
structure; an acetylating enzyme adds acetyl groups to
chloramphenicol)

Question 11

Resistance mechanisms genetically encoded in four classes

Answer 11

modification of drug target, enzymatic inactivation, removal via
efflux pumps, metabolic bypasses

Question 12

Spontaneous mutants resistant to rifampin can be obtained by

Answer 12

exposing a large population and selection

Question 13

Resistance genes can exist on mobile genetic elements and be
transferred by horizontal gene flow

Answer 13

Many mobile resistance genes encode enzymes that inactivate antibiotic (e.g., β-lactamase cleaves a ring structure; an acetylating enzyme adds acetyl groups to
chloramphenicol)

Question 14

Efflux pumps

Answer 14

are ubiquitous and transport various molecules, including
antibiotics, out of the cell. Efflux lowers the intracel- lular concentration of an antibiotic and thus allows the cell to survive at higher external concentrations.

Question 15

Efflux pumps are ubiquitous and transport various molecules, including
antibiotics, out of the cell

Answer 15

Lowers intracellular concentration, allowing cell to survive at higher
external concentrations
▪ Many act promiscuously and transport different antibiotic classes,
contributing to multidrug resistance
▪ AcrAB-TolC of E. coli is one of the best characterized; pumps out rifampicin, chloramphenicol, fluoroquinolones

Question 16

Biofilm growth leads to increased resistance

Answer 16

Makes infections difficult to treat
▪ AcrAB-TolC efflux pumps genes upregulated when cells enter biofilm
growth mode
▪ Pseudomonas aeruginosa encodes several multidrug efflux pumps
that are more active when cells grow in an attached state