Antibiotic resistance Flashcards
1
Q
Does antibiotic resistance mean that bacteria are more pathogenic?
A
NO
- We just have fewer antibiotic treatments available as they are resistant
- Harder to treat, not more virulent
2
Q
Why did we have to develop methicillin?
A
- Started to use penicillin- 8% resistant after 2 years, 70% resistant after 9 years
- Bacteria acquired a gene for lactamase enzyme, meaning that theu can degrade beta lactam penicillin
- Developed methicillin which was not degradable by lactamase enzyme
- 15 years later - methicillin resistant staph aureus (MRSA)
3
Q
What happens if here is co-infection and genetic exchange in animals?
A
- Can get genes that switch between different organisms
- Enterococci (Gram +ve gut organisms) are naturally vancomycin R+
- Acinetobacters (G-ve gut) are resistant to a range of different antibiotics
- The only drug we can use to treat MRSA is vancomycin
- If MRSA acquires vancomycin resistant genes from enterococci, they can become vancomycin R+
- Would have to use extremely toxic antibiotics
4
Q
How does a bacteria become resistant to a particular antibiotic?
A
- Directed at antibiotic itself (degrade or modify drug)
- Alter target (mutation in binding genes)
- Alter transport (actively pumping drug out - pump out faster than we can take in, never reach MIC) or porins no longer influx drug
- Inactivation enzymes
- Barriers to make membrane impermeable
- Efflux pumps
- Alter the binding targets
- Bypass/upregulate metabolic pathways to overcome inhibition - substrates can out-compete the inhibitors
5
Q
What are the three mechanisms of resistance?
A
- Genetic, non-genetic and natural resistance
6
Q
What is natural resistance?
A
- As opposed to acquired
- Drug must reach target - natural barriers, porins, export pump
- G+ve peptidoglycan is highly porous - no barrier to diffusion
- G-ve has outer membrane barrier - resistance advantage
- Single mutation in porins can lead to multiple resistance
7
Q
What genetic mechanisms are there?
A
- Chromosome-mediated - spontaneous mutation in target molecule or drug uptake system
- Plasmid-mediated - common in g-ve rods, transferred via conjugation -> multidrug resistance
- Antibiotic resistance spontaneous mutants will become dominant strain (sensitive strains are killed off)
- Our misuse of antibiotics is what starts these spontaneous mutations
8
Q
What are the 3 ways that allows gene transfer between bacteria?
A
- Transformation - takes up DNA from dead organisms around it; if the bit of DNA it takes up codes for beta lactamase, the recepient will be able to transcribe beta lactamase and become resistant
- Transduction - phage comes along, takes part of DNA from one bacteria and takes it to another
- Conjugation - certain species have pili that can bring them together and exchange DNA through (bacteria sex)
9
Q
How have bacteria become resistant to beta lactams?
A
- G+ve = beta lactamase + alteration of the transpeptidasse enzyme (PBP)
- G-ve = beta lactamase + alteration of porins
10
Q
What is co-amoxiclav?
A
- Clavulanic acid can bind to and inactivate beta lactamases, however has no anti-bacterial activity of its own
- If you mix clavulanic acid with a broad spectrum antibiotic, you can inhibit the beta lactamase and then use the amoxicillin to kill off the bacteria
11
Q
How do beta lactams usually work?
A
- Move through the porin in the outer membrane
- Bind to the PBP and stop the polymerisation of peptidoglycan sub units -> interrupts cell wall production
12
Q
What are the mechanism of beta-lactam resistance in G-ve bacteria?
A
- Porin mutation - cannot pass through outer membrane
- PBP mutates or bacteria acquires new PBP - can no longer bind
- Beta-lactamase in periplasmic space - degrades it
- Acquire alternative forms/mutation in efflux pumps - get pumped out faster than they can get it
13
Q
What does vancomycin do?
A
- Usually antibiotic blocks crosslinking reaction, after binding to the terminal D-ala-D-ala. This prevents the bacteria from polymerising the polysaccharide chain and blocks cross-linking
14
Q
How do bacteria acquire a resistance to vancomycin?
A
- Instead of having a terminal D-ala-D-ala, bacteria such as MRSA, can acquire a whole new gene operon (Van operon)
- This means that they have D-ala-D-lactate instead
- Vancomycin can therefore no longer bind to stop the polymerisation
15
Q
How can we prevent/overcome antibiotic resistance?
A
- Control use - dont use in animal feeds; complete course; dont overuse
- make new or modified drugs
- Combination therapies - multiple different targets
- Infection control - individual, ward and society
