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Medical Microbiology > Determination of Antibiotic Resistance > Flashcards

Determination of Antibiotic Resistance Flashcards

1
Q

What is antimicrobial resistance?

A

A natural phenomenon accelerated by use of antimicrobial medicines
Resistant strains survive and aggregate

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2
Q

How does AMR develop?

A

Microbes acquire mutations
Microbes acquire genetic information from other microbes to develop resistance

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3
Q

What are the types of AMR?

A

Antibacterial resistance
Antiviral resistance
Antiparasitic resistance
Antifungal resistance

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4
Q

Why is AMR a global concern?

A

Increases mortality
Challenges control of infectious diseases
Threatens a return into the pre-antibiotic era
Increases costs of healthcare
Jeopardises healthcare gains to society

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5
Q

What are the 3 main mechanisms that lead to drug resistance?

A

Modify drug target
Modify drug
Modify efflux and influx of drug

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6
Q

How does modification of drug target lead to drug resistance?

A

gyrase A mutation cause fluoroquinolone resistance

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7
Q

How are drugs modified?

A

Aminoglycoside modifying enzymes
Beta lactamases degrade B-lactam antibiotics

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8
Q

How does modification of efflux and influx of the drug lead to drug resistance?

A

Efflux pumps pump drug out the cells
Influx via porins

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9
Q

What are genetic mechanisms of resistance?

A

Chromosome-mediated - due to spontaneous mutation in the target molecule or the drug uptake system - mutants are selected, not induced
Mobile gene-mediated - common in gram -ve rods, multiple mechanism of transfer e.g. plasmids, carry genes conferring multidrug resistance

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10
Q

What is meant by selection of mutants?

A

Random mutation occurs causing resistance in that mutant
When antibiotic added to the population, the mutants are selected for and survive, creating a resistant species

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11
Q

Describe genetic transfer in bacteria

A

Mechanism for genetic heterogeneity and evolution
Rapid, cross-species
Virulence (toxins), drug resistance, antigens (immune evasion)

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12
Q

Give examples of fluoroquinolones

A

Ciprofloxacin
Moxifloxacin
Ofloxacin

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13
Q

What do fluoroquinolones do?

A

Bind to DNA gyrase (gyrA) and topoisomerase IV (parC)
Inhibits DNA replication

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14
Q

How does resistance to fluoroquinolones occur?

A

Mutations in the target gyrA and parC genes
Mutations usually in quinolone resistance-determining region (QRDR)

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15
Q

Give examples of aminoglycosides

A

Tobramycin
Gentamicin
Amikacin

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16
Q

What di aminoglycosides do?

A

Irreversibly bind to 16S rRNA in 30S subunit of ribosome
Inhibits protein synthesis

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17
Q

How does resistance to aminoglycosides occur?

A

Mutations in target rrs gene (16S rRNA)
Aminoglycoside modifying enzymes

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18
Q

What are the aminoglycoside modifying enzymes?

A

N-Acetyltransferase (AAC)
O-Adenyltransferase (ANT)
O-Phosphotransferase (APH)

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19
Q

What does AAC do?

A

Catalyses acetyl CoA-depedent acetylation of an amino group

20
Q

What does ANT do?

A

Catalyses ATP-dependent adenylation of hydroxyl group

21
Q

What does APH do?

A

Catalyses ATP-dependent phosphorylation of a hydroxyl group

22
Q

Give examples of beta-lactams

A

Penicillins
Carbapenems
Cephlasporins

23
Q

Give examples of penicillins

A

Ampicillin
Amoxicillin

24
Q

Give examples of cephalosporins

A

Cefazolin
Ceftriaxone

25
Q

Give examples of carbapenems

A

Meropenem
Ertapenem

26
Q

Give examples of monobactams

A

Aztreonam
Tigemonam

27
Q

What is the active structure in penicillin?

A

Beta-lactam ring

28
Q

What do beta-lactams do?

A

Bind to penicillin binding proteins (PBPs)
The bound PBPs are then unable to crosslink peptidoglycan chains
Bacteria unable to synthesis cell wall and bacteria are lysed

29
Q

How does resistance to beta-lactams develop?

A

Mainly due to beta-lactamase enzymes

30
Q

What do beta-lactamases do?

A

Hydrolyse and break the beta-lactam ring, inactivating beta-lactam
Can be overcome by adding beta lactamase inhibitors

31
Q

Give examples of beta-lactamase inhibitors

A

Tazobactam
Clavulanic acid

32
Q

What are extended spectrum beta-lactamases (ESBLs)?

A

Carried on plasmids that have other resistance genes - results in multidrug resistance

33
Q

Give an example of an ESBL

A

Carbapenemases - they inactivate carbapenems, penicillins and extended spectrum cephalosporins

34
Q

What do efflux pumps do?

A

Transport proteins that can expel toxic substances from the cell

35
Q

Where are efflux pumps found?

A

In gram +ve and -ve species

36
Q

What are the 5 families of efflux transporters in bacteria?

A

Major facilitator (MF)
Multidrug and toxic efflux (MATE)
Resistance nodulation division (RND)
Small multidrug resistance (SMR)
ATP binding cassette (ABC)

37
Q

What is the genetic basis of antibiotic resistance in Neisseria gonorrhoeae?

A

Acquired genes
Mutations
Gene mosaics with or without superimposed mutations

38
Q

What mutations of Neisseria gonorrhoeae provide resistance to penicillin?

A

penA - PBP2
ponA - PBP1
penB - outer membrane porin
mrR regulator - controls mtrCDE efflux pump operon
penC - secretin PilQ of the type IV pilin

39
Q

What acquired genes in Neisseria gonorrhoeae provide resistance to penicillin?

A

plasmid-mediated TEM-1 penicillinase - blaTEM-1

40
Q

How are N. gonorrhoeae resistant to tetracycline?

A

Acquisition of plasmid-mediated tet(M) ribosomal protection protein
A combination of mtrR, penB and rpsJ gene mutations

41
Q

What makes N. gonorrhoeae resistant to fluroquinolones?

A

Mutations in gyrA and parC in QRDR

42
Q

What makes N. gonorrhoeae resistant to cephalosporin?

A

Multiple alterations in penA (PBP2), often + mosaic gene exchange with other Neisseria species
High level ceftriaxone resistance - point mutations superimposed upon mosaics

43
Q

What makes N. gonorrhoeae resistant to azithromycin?

A

Mutations to multiple 23S rRNA gene copies - single mutation + internal recombination (high level resistance)

44
Q

What gives N. gonorrhoeae low level resistance to azithromycin?

A

mtr mutations
acquired mphA
mefA-E (efflux pumps)
ermABCF (ribosomal methylases)

45
Q

How can drug resistance phenotype be determined?

A

Culture based methods
Molecular diagnostics
Genome sequencing

Medical Microbiology (23 decks)

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