Bacterial Genetics and Antibiotic Resistance Flashcards
What class of antibiotics inhibit DNA gyrase and give an example of one?
Fluoroquinolones
- ciprofloxacin
(Also novobiocin but this is not a fluoroquinolone)
Through which mechanisms can bacteria become resistant to antibiotics?
- The part of the bacteria which the antibiotic targets becomes mutated
- The bacteria breaks down the antibiotic
- The antiobiotic breaks down the antibiotic
- The antibiotic becomes effluxed
Give an example of an antibiotic which has become less effective due to mutation of the drug target as a mechanism of resistance
Rifampicin
- A single nucleotide/amino-change in rpoB alters affinity for drug without affecting function
What does Rifampacin work against and by what mechanism?
Used in the traetment of TB (in combination with other drugs and used in prophylaxis)
- Inhibits RNA polymerase
What other drugs are vulnerable to resistance due to target site mutations (other than rifampacin)?
- Streptomycin
- Ciprofloxacin
Give an example of a class of drugs which is vulnerable to resistance through bacteria being able to modify them?
Aminoglycosides (e.g streptomycin)
- The bacteria add small molecules to the drug to prevent it binding to the ribosome
Give examples of antibiotics which can be evaded by efflux
- Tetracycline
- Chloramphenicol
- Fluoroquinolones
- Beta-lactams
Efflux mechanisms may give resistance to multiple antibiotics
How may bacteria develop resistance through an efflux pump?
- May up-regulate existing pump (by mutation - may arise during treatment)
- Bacteria may acquire genes for new pump
How much more DNA do humans have in comparison to bacteria?
About 1000 times more
How much less genes do bacteria have in comparison with humans?
Only around 10 times less
How do bacterial chromosomes compare to human?
- Bacterial chromosomes are haploid and circular (human are diploid and linear)
What is the bridge called that is used to transfer plasmids from one bacteria to another?
Pilus
What is an insertion sequence?
- Elements of DNA which are capable of excision and inserion into new locations in chromosome or plasmid
- Most basic transposable element
- Sits within genome and has inverted repeats either side of it with genes in between which code for it to be excised to another position in the genome
What are simple transposons?
Insertion sequences which have additional gene(s) which often code for bacterial resistance
What are complex or composite transposons?
Multiple genes which are flanked by insertion sequences
What do transposases?
enzymes that identify the inverse terminal repeat sequences within the DNA and proceed to bind and excise (cleave) the DNA transposons in between the terminals
What is an integron?
- Special class of composite element which carry gene cassettes
- They can carry multiple resistance genes
- When they are transferred they transfer a whole set of genes together
What are the functions of transposons?
- Transfer genes from plasmid to plasmid
- Conjugative transposon transfer from one cell to another (cf conjugative plasmids)
- Transfer genes between plasmid and chromosome
- Pick up chromosomal genes
How many cassettes can integrons carry?
Up to 5
Describe the mechanism of transformation
- Naked DNA is picked up from the environment
- Can replace existing chromosomal gene with a resistant variant
Give an example of a baceria that has become resistant through transformation
Streptococcus pneumoniae (penicillin resistance)
Where do resistance genes originate?
- The environment (where bacteria and antibiotic have co-evolved) (e.g CTX-M Beta-lactamase)
- Also can develop resistance to synthetic antimicrobials such as sulphonamides
What can be done to tackle antibiotic resistance?
- Develop new antimicrobials
- Monitor spread of resistance
- Antibiotic stewardship (control of prescribing)
- Point of care diagnostics (know immeaditely what bacteria has infected the patient and treat with correct antibiotic accordingly)
