14- Antibiotic Resistance

Question 1

what is AMR/ antimicrobial resistance?

Answer 1

the ability of a microbe to withstand/survive the effects of antimicrobials it would normally be susceptible to

Question 2

concerns with AMR?

Answer 2

human and financial cost
increases mortality
challenges control of infectious diseases
threatens a return to the pre-antibiotic era
increases the costs of health-care
jeopardises health-care gains to society

Question 3

list mechanisms for antibiotic resistance

Answer 3

altered/ new target
overproduction of target
efflux pumps - altered transport
intrinsic impermeability - natural resistance
degrading/modifying antibiotic
metabolic by-pass

Question 4

how does altering/ creating a new target confer antibiotic resistance?

Answer 4

drug can’t bind to its original target - doesn’t have affinity for the new/ altered target

bacteria can continue invasion, antibiotic is ineffective

Question 5

how do efflux pumps confer antibiotic resistance?

Answer 5

antibiotic tries to enter bacterial cell - gets actively pumped out by efflux pumps

can’t reach an effective conc/MIC inside the bacteria to kill it

Question 6

how does metabolic by-pass confer antibiotic resistance?

Answer 6

antibiotic made less effective due to changes in metabolic pathways

Question 7

how does overproduction of the target confer antibiotic resistance?

Answer 7

e.g. with trimethoprim – overproduction of dihydrofolate reductase means trimethoprim will bind to some, but leave lots left unbound

allows for folic acid metabolism and synthesis to occur = DNA synthesis can occur and bacteria can continue growing

Question 8

three mechanisms for bacteria becoming antibiotic resistant?

Answer 8

natural resistance
genetic (acquired) mutations
non-genetic mechanisms (circumstantial)

Question 9

describe natural antibiotic resistance

Answer 9

gram neg bacteria have an impenetrable outer membrane with porins that regulate passage of molecules in and out of bacteria - can prevent certain antibiotics getting in
- mutations in porins can confer multiple antibiotic resistances

pathways in anaerobic pathways targeted by antibiotics won’t work for aerobes and vice versa - different enzymes and pathways for both

Question 10

describe how chromosomal mutations confer genetic acquisition of antibiotic resistance

Answer 10

spontaneous mutations in the target or drug uptake system can confer antibiotic resistance, but this won’t be known until the mutant is exposed to the antibiotic

antibiotic resistance mutation is selected for as those without it die off, an mutant multiples, becomes the dominant form in the bacterial species

Question 11

three methods for horizontal acquisition of (antibiotic resistance) genes?

Answer 11

conjugation
transformation
transduction

Question 12

conjugation - mechanism for the horizontal acquisition of (antibiotic resistance) genes?

Answer 12

cells in contact with one another produce a sex pilus which connects them - DNA transferred from one bacterium to another mediated by plasmids

becomes antibiotic resistant if it acquires the right genes

Question 13

transformation - mechanism for the horizontal acquisition of (antibiotic resistance) genes

Answer 13

uptake, integration and functional expression of fragments of extracellular DNA - extrac. DNA available following bacterial cell lysis and release of genetic material

if bacteria incorporates the extrac. DNA into tis genome and it confers resistance = bacteria acquires it

Question 14

transduction - mechanism for the horizontal acquisition of (antibiotic resistance) genes

Answer 14

the transfer of bacterial DNA by bacteriophages from a previously infected donor cell to the recipient cell - obtain resistance from other bacterial DNA

Question 15

how does gram neg bacteria confer beta lactam resistance?

Answer 15

beta-lactamase/ penicillinase = destroys active part of penicillin

altering transpeptidase enzyme PBP = penicillin has nowhere to bind

Question 16

how does gram pos bacteria confer beta lactam resistance?

Answer 16

beta lactamase/ penicillin

porins on outer membrane altered = blocks antibiotic entering

Question 17

what is Augmentin? how does it overcome beta lactam resistance?

Answer 17

beta lactamase drug that binds to and inactivates beta-lactamase

clavulanic acid and amoxicillin together - only have anti-bacterial activity together

mechanism:
clavulanic acid binds beta lactamase and inactivates
allows antibacterial activity from amoxicillin

Question 18

four mechanisms for beta lactam/ penicillin resistance in bacteria

Answer 18

produce penicillinase/ beta lactamases that cleave beta lactam ring

acquire alternative forms/ mutations in PBPs

acquire alternate forms/ mutations in porins
= prevents penicillin entering cell

acquire alternate forms/ mutations in efflux pumps = penicillin pumped out faster

Question 19

vancomycin resistance - how?

Answer 19

bacteria acquires van operon during transcription, makes D-ala-D-lactate instead of D-ala-D-ala

vancomycin can’t bind to D-ala-D-lactate = different structural target, can’t inhibit cell wall synthesis

Question 20

describe non-genetic mechanisms of acquiring resistance

Answer 20

bacteria somewhere inaccessible to antibiotics - e.g. abscess, deep tissues

bacteria in stationary phase aren’t actively proliferating, remain dormant = drugs ineffective

biofilms - extrac. protective matrix self-produced by aggregated bacteria protect against antibiotics

Question 21

at what phase of bacterial infection is it best to use antibiotics?

Answer 21

log phase - actively dividing, producing cell walls

Question 22

methods for overcoming/ preventing resistance

Answer 22

control use - complete antibiotic course, appropriate prescribing

new/ modified drugs

combination therapy - same mutation likely won’t confer resistance to two different antibiotics

infection control - prevent the infection in the first place