Lecture 9 Flashcards
What can cause antibiotic resistance?
- Inappropriate use of antibiotics including animal husbandry and agriculture
- Weak surveillance
- Poor infection prevention
- Insufficient diagnosis
- Overuse
- Disruption in commensal microflora
- Antibiotics in water supplies
Why is resistance a problem
- Increased mortality
- Treatment failure
- Increased healthcare cost
- Resistance in community
Intrinsic resistance
Resistance due to genetic, structural or physiological state of organism - defines spectrum of antibiotic sensitivity
Acquired resistance
Resistance due to ALTERED genetic, physiological or structural state of organism - induced genetic mutation, or acquired by transfer of genetic material
Name ways microorganisms can be resistant to antibiotics
- Lack of/Altered target binding site
- Efflux pump
- Enzyme that inactivates antibiotics
- Alternative metabolic pathway
- Decreased permeability/loss of porin channels
- Formation of biofilm
How do Quinolones become resistant
Decreased uptake and altered DNA gyrase binding site
Where are resistance genes carried?
Chromosomes or plasmids
Transduction
- Phage infects bacterial donor cell
- Phage DNA and proteins made - bacterial chromosome broken down
- Donor cell lyses and releases phage particles containing bacterial DNA by recombination
- Phage with bacterial DNA infects host cell (recipient cell)
- Recombination occurs producing recombinant cell with genotypes containing elements of donor and recipient cells
Conjugation
- F+ donor containing F plasmid can synthesize sex pilus
- Sex pilus contacts recipient F- cell
- Plasmid activated for transfer after endonuclease cleaves 1 strand of DNA at origin of transfer
- Sex pilus retracts and pulls donor and recipient cells together - F-plasmid transferred as a ssDNA molecule
- Complementary strands syntheized in donor and recipient cells - Both cells are F+ and synthesize sex pilus
Transformation
Recipient cell takes up donor DNA
Recombination occurs between donor and recipient DNA
What is used to harpoon DNA in environment?
Pili
Clockwise: Pili grabs DNA, and then retracts
Beta-lactam mechanism
Bind and inhibit carboxypeptidases and transpeptidases (cell wall synthesizing enzymes)
These enzymes catalyse D-ala-D-ala cross linkages of peptidoglycan wall
How does penicillin stop cell wall synthesis
Bind and inactivate PBPs
Weakens cell wall, leads to cell lysis
Resistance to beta-lactams
Beta-lactamase hydrolyses the beta lactam ring - results in
What are extended spectrum beta-lactamases (ESBL)
Group of enzymes produced by gram-negative bacteria - responsible for resistance
- Gene for resistance carried on plasmid - transferable from one bacteria to another
- seen in community isolates
- Cause hospital outbreaks - treated with limited antibiotics
