Mechanisms of Drug Resistance

Question 1

Genetic composition of the cell undergoes spontaneous alteration by

Answer 1

Mutation of gene transfer

Question 2

Provides a strong selective pressure in favor of the resistant cell by preventing growth of the wild-type, sensitive cells

Answer 2

Drug

Question 3

May have mutagenic properties and non-specifically increase the probabilities of many kinds of mutation

Answer 3

Bacteriostatic drugs

Question 4

Estimated to cause more deaths in the US than AIDs

Answer 4

Methicillin-resistant Staphylococcus Aureus (MRSA)

Question 5

Anti-microbial resistance is more prevalent in strains that cause infections in

Answer 5

Hospitals

Question 6

During outbreaks of infections, patients with resistant strains are more likely to have received prior

Answer 6

Animicrobial therapy

Question 7

Areas in hospitals with highest antibiotic use have highest incidence of

Answer 7

Drug resistant bacteria

Question 8

What are the four mechanisms by which bacteria can acquire drug resistance?

Answer 8

Transformation, Transduction, Conjugation, Transposition

Question 9

Small pieces of DNA containing genes for drug resistance are taken up from the environment and incorporated into the genome of a drug-sensitive bacterium

Answer 9

Transformation

Question 10

Resistance genes are transferred from one bacterium to another by a bacteriophage

Answer 10

Transduction

Question 11

Drug resistance genes contained in a plasmid are transferred from one cell to another through a direct connection formed by a pilus

Answer 11

Conjugation

Question 12

Allows resistance genes to move between plasmid and chromosomal (genomic) DNA

Answer 12

Transposition

Question 13

The first biochemical mechanism of drug resistance is decreased intracellular drug level due to either

Answer 13

Decreased drug entry or increased drug efflux

Question 14

Gm- bacteria with mutations that alter porin proteins, thereby decreasing passive drug diffusion is an example of

Answer 14

Decreased intracellular drug level

Question 15

Resistance to tetracyclines can occur through acquisition of genes that encode an active

Answer 15

Efflux of the drug

Question 16

The second mechanism for drug resistance is increased

Answer 16

Drug inactivation

Question 17

Can produce enzymes that render antibiotics biologically inert

Answer 17

Bacteria

Question 18

An example of this is the enzymatic cleavage of penicillins and cephalosporins by

Answer 18

B-lactamases

Question 19

Drug resistance can also occur from decreased conversion of a drug to a more

Answer 19

Active compound

Question 20

Decreased conversion of a drug to a more active compound occurs most often with drugs that act as

Answer 20

Antimetabolites

Question 21

Resistance to the antifungal agent 5-flucytosine due to decreased activity of UMP pyrophosphorylase is an example of

Answer 21

Decreased conversion of a drug to a more active compound

Question 22

Drug resistance can also occur by increased conversion of a metabolite that functions as a

Answer 22

Drug antagonist

Question 23

If the drug acts as an antimetabolite, then increased production of the normal metabolite will compete for the drug effect and lead to

Answer 23

Resistance

Question 24

An example of increased concentration of a metabolite that antagonizes drug action is the resistance to sulfonamides by an increase in

Answer 24

p-aminobenzoic acid (PABA)

Question 25

An altered amount of target enzyme or receptor can also confer

Answer 25

Drug resistance

Question 26

Mutation in a regulatory gene (e.g., a repressor) can control the expression of the gene encoding the

Answer 26

Target

Question 27

When the gene for the receptor undergoes a mutation that changes the conformation of the drug binding site, we see a

Answer 27

Decreased affinity of receptor for drug

Question 28

Trimethoprim resistance by producing DHFR with reduced affinity for the drug is an example of

Answer 28

Decreased affinity of the receptor for the drug

Question 29

Mutants deficient in autolytic enzymes, which breakdown sections of the proteoglycan (PG) matrix during growth can cause

Answer 29

Drug resistance

Question 30

In the absence of autolytic enzymes, drugs that inhibit cell wall synthesis

Answer 30

Bacteriostatic rather than bactericidal (tolerance)

Question 31

A unique form of drug resistance is an alteration of an enzymatic process that is unaffected by the drug, but is necessary for the drug’s

Answer 31

Cytotoxic affect

Question 32

Binds D-Ala-D-Ala moiety and interferes with formation of PG matrix

Answer 32

Vancomycin

Question 33

Produces enzymes that generate D-Ala-D-lactate termini that can form PG matrix, but do not bind vancomycin

Answer 33

VanHAX Operon

Question 34

Resistance is diminishing the effectiveness of

Answer 34

Vancomycin

Question 35

Administration of sub-inhibitory doses of antibiotics promotes the selection of

Answer 35

Resistant subpopulations

Question 36

Administer combinations of two drugs with different mechanisms of action and different biochemical pathways of resistance when performing

Answer 36

Antimicrobial Chemotherapy

Question 37

If resistance mutation frequency is 10-6 for each drug alone, then it will be 10-12 when both drugs are administered in

Answer 37

Combination

Question 38

To combat bacterial resistance mechanisms, we want to develop inhibitors of drug-inactivating proteins and efflux transporters. An example of this is the use of

Answer 38

B-lactamase inhibitors