Antibiotic Resistance Flashcards
Antibiotic resistance bacteria
- Not more pathogenic than normal bacteria but there is less antibiotics to treat them
- We have some in our body that do not cause disease:
- > Enterococci which is G +ve, lives in the gut is resistant to vancomyocin.
- > Acinetobacter which is G -ve, lives in the gut is resistant to multiple drugs
- > MRSA which is G +ve, lives in the gut and wound but isn’t resistant.
How is the superbug formed?
Combination of antibiotic resistant bacteria that although individually do not cause disease, because they all live together they are able exchange genetic material which leads to co-infection leading to vancomyocin resistant MRSA.
6 mechanisms of antibiotic resistance
- Drug inactivation
- Mutated/altered target or acquisition of a new target
- Mutated or new porins
- Intrinsic impermeability - NATURAL
- Overproduction of target
- Metabolic by pass - D-ala
Drug inactivation - beta lactam enzymes
- The bacteria acquires an enzyme which breaks down the drug or the active component of the drug.
- For example; acquires an enzyme which breaks down the beta lactam ring in the beta lactams and therefore the drug can no longer inhibit cell wall formation
- A lot of bacteria has this resistance
Mutated/altered target or acquisition of a new target
- RNA pol can get mutated which means the drug can no longer bind to it. this happens in romaficin resistant TB
- Can get acquisition of a new target protein/enzyme such as in MRSA when it gets a new PBPIIA meaning the beta lactam can no longer bind and inhibit cell wall formation.
- Can get mutation in the DNA gyrase enzyme, meaning again the drug such as Quindilones isn’t able to bind and inhibit coiling and uncoiling.
- Mutation in ribosomal RNA means the drug won’t be able to block the protein synthesis.
Mutated or new porins
- The antibiotics needs porins in order to enter Gram -ve bacteria and the bacteria is able to exchange genes and acquire genes for a completely new porin.
- This means the drug will no longer be able to enter or if it does the bacteria can pump it out via the porin.
- They can also acquire efflux pump which pump out all the intracellular components the bacteria doesn’t want including antibiotics and therefore the MIC will never be reached.
Intrinsic impermeability
- This is a natural mechanism some bacteria such as G -ve bacteria have, they DO NOT ACQUIRE MUTATION
- They have impermeable outer membranes which means they are resistant to a lot of bacteria such as celosia which causes UTI and pseudomonas which causes cystic fibrosis.
Overproduction of target
- The bacteria can upregulate the genes for the enzymes and their natural substrate so despite the antibiotic acting as a competitive inhibitor the natural substrate is able to bind and the bacteria is able to continue making folic acid
- They can also upregulate the metabolic pathway that increases the synthesis of the natural synthesis for example for folic acid
Metabolic by pass - D-ala
- Bacteria can acquire a whole set of new genes that encode a whole different biosynthetic pathway which is different to D-ala on peptidoglycan so the beta lactam is no longer able to work.
- They can generate D-lac which is different and therefore leads to vancomyocin resistance
How do you get acquired mutations?
- Via chromosomes acquisition of genes
- Via plasmid acquisition of genes
Explain how mutations are acquired via chromosomes acquisition of genes
- Bacteria replicate at a high rate and therefore they are likely to acquire a large number of mutants.
- If by chance one of these mutations is antibiotic resistance, under the pressure of antibiotic usage, this mutation will be selected for.
Explain how mutations are acquired via plasmid acquisition of genes
Common in G -ve, transferred via conjugation and multi-drug resistance
How does gene transfer in bacteria occur?
Through heterogenicity and evolution. The rapid cross species exchange leads to formation of new toxins, drug resistance and immune evasion.
3 ways the gene transfer in bacteria can occur
- Transformation: uptake naked DNA from a bacterium that has lysed into another healthy bacteria for example in Streptoccoi
- Transduction: Bacteria gets infected with a phage (virus) and the virus would’ve contained the DNA from a lysed bacterium
- Conjugation: This is when 2 bacteria come together to form a bridge called pili and exchange chromosomal and plasmid DNA.
G+ ve in beta lactam resistance
- Acquire beta lactamase enzymes such as Penicilinase which means they are destroying the beta lactam ring and the 3D structure of the drug.
- Acquire alteration in the transpeptidase enzyme such as PBP
