Antibiotic resistance Flashcards
What is antimicrobial resistance
AMR is the ability of a microbe to withstand/survive the effects of antimicrobials it would normally be susceptible to
Why sis antibiotic resistance a global health concern
- Increases mortality
- Challenges in the control of infectious diseases
- Threatens a return to the pre-antibiotic era
- Increases the costs of health-care
- Jeopardises health-care gains to society
What are the methods of antibiotic resistance
Directed at antibiotic itself:
- Degrading the drug
- Modifying the drug
New or altered target:
- Antibiotic no longer binds
- e.g. PBPs – PBP2a in MRSA
Altered transport:
- Actively pumping drug out – efflux pump
- Porins no longer influx drug
Metabolic by-pass:
- Metabolic change e.g. D-ala-D-lac and vancomycin
How do bacteria become resistant to antibiotics
- Natural resistance
- Genetic Mechanisms - acquired
- Non-Genetic Mechanisms (growth phases) - tolerance
How does natural resistance work
- Natural barriers
- Porins
- Export pump
How does genetic mechanism lead to resistance
- Chromosomal mutations
Horizontal acquisition:
- Conjugation
- Transformation
- Transduction
How does mutations lead to resistance
Chromosome mediated mutations occur in:
- target molecule
- drug uptake system
Mutants are selected; they are not induced
Why does genetic transfer occur in bacteria
- Mechanism for genetic heterogeneity and evolution
- Rapid, cross-species
- Virulence (toxins), drug resistance, antigens (immune
evasion)
Explain the conjugation mechanism in the horizontal acquisition of antibiotic-resistant genes
Process requiring cell to cell contact via cell surface pili (sex pilus) or adhesins, through which DNA is transferred from the donor cell to the recipient cell
Explain the transformation mechanism in the horizontal acquisition of antibiotic-resistant genes
The uptake, integration, and functional expression of naked fragments of extracellular DNA
Explain the transduction mechanism in the horizontal acquisition of antibiotic-resistant genes
The transfer of bacterial DNA by
bacteriophages from a previously infected donor cell
to the recipient cell
What mechanisms do bacteria use to be resistant to Beta-lactams
- Beta-lactamase
- Alteration of transpeptidase enzyme in gram positive
- Porin alteration in gram negative
How does co-amoxiclav work
- Contains Clavulanic acid and amoxicillin
- Clavulanic acid binds to lactase enzyme and allows amoxicillin to work normally
How does vancomycin resistance work
- Acquisition of van operon by transposition
- Makes D-ala-Dlactate
- Prevents vancomycin binding
How does non-genetic mechanisms lead to antibiotic resistance
- Inaccessibility to drugs
- Stationary phase/vegetations and biofilm
