Genetics of Bacterial Antibiotic Resistance Flashcards
describe a prokaryote
- Cell wall
- DNA is within the cytoplasm of the cell
- Has a flagella
- Smaller 2um
Describe a Eukaryote
- Nucleus
- Cytoplasm
- Organelles
- 20um
- Has a cell membrane
What must antibiotics be
- Must be toxic to the bacteria but not the host
when did resistance to antibiotic develop
- From the first use of antibiotics there were some bacteria that couldn’t be inhibited by some antibiotics
Name mechanisms of action of antibiotics
- inhibit cell wall synthesis
- inhibit protein synthesis
- folate metabolism is also inhibited
How does antibiotic resistance develop
- Mutation of the drug target
- Breakdown of the antibiotic
- Modification of the antibiotic
- Efflux of the antibiotic
How does rifampicin works
- Rifampicin inhibits RNA polymerase preventing RNA production and is bactericidal
Give examples of target site mutations for drugs
- Rifampicin
- streptomycin
- ciprofloxacin
Describe how the bacteria can break down the antibiotics
- Resistance bacteria degrade the B lactam – produces a beta lactamase enzyme that breaks down penicillin
Describe how bacteria can modify the antibiotic to prevent it from working
- Bacteria acquire genes encoding aminoglycoside modifying enzymes
- These add small molecules to the drug to prevent it binding
- Produce enzymes that modifies the aminoglycoside so it can no longer bind to the ribosome
Describe how bacteria can effect the efflux of antibiotics
- Bacteria may up-regulate existing pump
- By mutation – may arise during treatment
- Bacteria may acquire genes for new pump
what antibiotics are effected by efflux mutations
- Tetracycline
- Chloramphenicol
- Fluoroquinolones
- Beta lactams
How can resistance genes be acquired by bacteria
- plasmid transfer
- transposable elements
- transformation
describe how resistance genes can be acquired by bacteria by plasmid transfer
F (fertility) factors are classic example of conjugative plasmids
F+ cells produce F pili involved in making contact with recipient
plasmid transfer involves replication
How can resistance genes be acquired via transposable elements
DNA sequences capable of excision and insertion into new locations in chromosome or plasmid
Simplest elements are insertion sequences (IS) which encode transposase gene flanked by inverted repeats
Many genomes contain several ISs, some in multiple copies
- Transposition results in the duplication of the target sequence
transfer genes from plasmid to plasmid
conjugative transposons transfer from one cell to another (cf conjugative plasmids)
transfer genes between plasmid and chromosome
pick up chromosomal genes
What is an integron
special class of composite element carrying gene cassettes
Describe the structure of integrons
Each integron contains up to 5 cassettes
More than 60 different cassettes have been found
Most are antibiotic resistance determinants
How can resistance genes be acquired by transformation
transfer of naked DNA
DNA integrated into chromosome by
homologous recombination
Replacement of an existing chromosomal gene with a resistant variant
E.g. Streptococcus pneumoniae penicillin resistance
Where do resistance genes originate
Antibiotics are natural products
e.g. penicillin from mould
Bacteria in the environment have co- evolved
e.g. CTX-M β-lactamase originated in Kluyvera spp found in soil
What can we do about antibiotic resistance
- Develop new antimicrobials
- Antibiotic development is decreasing
- If we did get a new development we wouldn’t want to use it therefore drug companies wouldn’t make the money back that it costs to develop it
