Antibiotic Resistance Flashcards
What are the consequences of antibiotic resistance?
- Increases mortality
- Challenges control of infectious diseases
- Threatens a return to the pre-antibiotic era
- Increases healthcare costs
- Jeopardizes healthcare gains to society
Describe the pathogenicity of drug resistant bacteria
Drug resistant bacteria are NOT MORE pathogenic - We just have fewer antibiotic options for treatment as they’re resistant to antibiotics
How do bacteria become resistant to ꞵ-lactams?
Beta-lactamase enzyme acquired by resistant bacteria to destroy antibiotic ꞵ-lactams ring - make it inactive
How do mutations cause resistance?
If RNA pol undergoes a simple mutation, the drug is no longer able to bind (common in TB)
How do drug targets become resistant?
Acquisition of a new drug target e.g. PBP2a in MRSA - no longer inhibited by ꞵ-lactams
What are the effects of bacterial enzyme mutations?
Mutations in DNA gyrase and polymerase mean non-functional quinolins etc.
What are the consequences of bacterial porin mutations?
Mutations in porins causes alterations to their transportation properties:
- Upregulation of efflux pumps
- Blockage of porins
Explain how some bacteria are naturally drug resistant
Some bacteria are intrinsically impermeable - their membranes are so naturally impermeable, antibiotics have no effect (majorly in Gram -ve)
Describe how metabolic changes cause resistance
Metabolic change D-ala-D-lac and vancomycin
What are the 3 mechanisms of resistance?
- Natural resistance
- Genetic Mechanisms; acquired
- Non-Genetic Mechanisms (growth phases)
What is the natural resistance within bacteria?
> not acquired
Natural barriers for drug reaching target: porins, export pump
G+ve peptidoglycan - highly porous; no barrier to diffusion
G-ves outer membrane; barrier resistance advantage
Porins; single mutation leads to multiple resistance
What are the 2 types of genetic mechanisms of resistance?
- Chromosome-mediated
- Plasmid-mediated
What causes chromosome mediated genetic resistance?
Due to spontaneous mutation:
- in target molecule
- in drug uptake system
Describe plasmid mediated drug resistance
- Common in Gram-ve rods
- Transferred via conjugation
- Multidrug resistance
How do bacterial mutants arise causing genetic resistance to antibiotics?
Mutants are SELECTED ; they are NOT induced
How does antibiotic resistance cause selection for resistant bacteria?
Random mutation occurs - has no major effect as overpowered by many sensitive bacteria surrounding it
Antibiotic administered, killing all sensitive bacteria, leaving mutated bacteria - selection antibiotic resistance
What are the 3 methods of gene transfer in bacteria?
- Transformation
- Transduction
- Conjugation
What is transformation?
Uptake of naked DNA that is lysed from another bacteria (e.g. streptococci)
What is conjugation?
2 bacteria come together and form pili where (chr./plasmid) DNA is exchanged - not all bacteria can do this
What is transduction?
Phage infection takes fragment of DNA from one bacterial host to the next
Outline how Gram +ve bacteria become resistant to ß-lactams
ß-lactamase (Penicillinase)
Alteration of transpeptidase enzyme (PBP)
How do Gram -ve bacteria become ß-lactam resistant?
ß -Lactamase (Penicillinase)
Alteration of porins
How do bacteria become penicillin resistant?
Penicillinase destroys active part of penicillin molecule so that it is no longer a competitive structural mimic of the enzymes involved
What is augmentin / Co-amoxiclav?
Antibiotic combination = Clavulanic acid + amoxicillin
What is the role of Clavulanic acid?
Clavulanic acid is an inhibitor of a ꞵ-lactamase enzyme but has no antibacterial activity alone
Outline how beta-lactam resistance is acquired
- Porin mutates / new porin type acquired - multiresistant
Ꞵ-lactam unable to cross outer membrane - PBP mutates / bacteria acquires new PBP; even if ꞵ-lactam gets through porin, its unable to bind to PBP enzymes
- Bacteria acquires (extended) ꞵ-lactamase enzymes that destroy ꞵ-lactams entering bacteria
What are the different mechanisms of penicillin resistance?
Produce penicillinases / beta lactamases that cleave beta lactam ring
Acquire alternative forms of / mutations in
- efflux pumps
- porins
- penicillin binding proteins (PBPs)
How is MRSA treated?
Only effective treatment is vancomycin, a 1.5 kDa glycopeptide
How does vancomycin treat MRSA?
Vancomycin sits on top of the terminal D-ala-D-ala peptides to inhibit peptidoglycan cross linking from occurring
How does vancomycin resistance arise?
Bacteria that are vancomycin resistant acquire van operon structure by transposition
Makes D-ala-D-lactate rather than D-ala-D-ala - prevents vancomycin binding
What are the non-genetic mechanisms of antibiotic resistance?
Inaccessibility to drugs (e.g., abscess, TB lesion)
Stationary phase/vegetations and biofilms (non-susceptible to inhibitors of cell wall synthesis)
