L20 Flashcards
Five main bacterial antibiotic resistance mechanisms
- Altered antibiotic target
- Inactivate antibiotic
a. Degrading the antibiotic
b. Chemically modify antibiotic - Reduced antibiotic accumulation
- Alternate pathway to bypass the inhibited one
- Altering the target of the antibiotic
- Target Protection - block access
- Target Modification - mod target
- Insensitive Functional Target - alt enzyme
Target Protection
- Resistance protein blocks access of antibiotic target
Target Modification
–Resistance enzyme modifies antibiotic target
–e.g. vancomycin R - arises when bacteria change the terminal D-ala in the pentapeptide of peptidoglycan into D-serine or D-Lactate, so vancomycin cannot bind
Insensitive Functional Target
–Resistance protein is an alternative enzyme that is insensitive to antibiotic
–e.g. β-lactam R - MRSA produces an alternative PBP MecA which has low binding affinity for all β-lactams
2a. Degrading the antibiotic
–e.g. hydrolysis of the β-lactam ring of penicillins and cephalosporins by penicillinase (β-lactamase) enzymes
2b. Modifying the antibiotic
- Chemically altering antibiotic
- e.g. acetyltransferase adds an acetyl group to aminoglycosides or chloramphenicol, inactivating them
- Reduced antibiotic accumulation
* Antibiotic efflux
–Rapid extrusion of antibiotic via efflux pump –e.g. multidrug exporter RND system of Gram negs can pump out quinolones, tetracycline and chloramphenicol
–extrusion is energy-dependent
–Note: bacteria can also reduce uptake
- Alternate pathway to bypass the inhibited one
* Target bypass
–e.g. Enterococci are intrinsically resistant to sulphonamides because they are able to use pre-formed folic acid from their environment (unlike other bacteria)
–Group A Streptococcus reduced folate transporter
- Vertical gene transfer
transfer of genes from parent to progeny
–bacteria have this, but as they don’t reproduce sexually so only limited genetic variation (via mutation)
- Horizontal gene transfer (HGT)
transfer of genes from one independent, mature organism to another
–HGT is of major importance in bacterial evolution, including the gain of antibiotic-resistance genes
Horizontal gene transfer is a one way process [t/f]
True
How is HGT a one way process?
- Donor DNA enters a recipient cell
- If donor DNA contains genes already present in recipient, recipient
becomes temporarily a partial diploid for those genes - The donor DNA then has four possible fates in recipient cell
–Integration via recombination with the recipient’s genome
–Self-replication of the donor DNA (if plasmid)
–No replication and loss of donor DNA
–Degradation of donor DNA
The donor DNA then has four possible fates in recipient cell if genes are present in recipient already
–Integration via recombination with the recipient’s genome
–Self-replication of the donor DNA (if plasmid)
–No replication and loss of donor DNA
–Degradation of donor DNA
Mobile genetic elements:
DNA segments that can move to different locations on genomes and/or move from cell to cell. Includes
1. Plasmids
2. Transposable element
3. Integron
Mobile genetic elements: Plasmid
double-stranded DNA molecule, usually circular, that can exist and replicate independently of the chromosome
- R plasmid/ Resistance plasmid:
a plasmid bearing one or more antibiotic-resistance genes
The first plasmid discovered was the
F plasmid
(or F factor)
Mobile genetic elements) Transposable element
small linear DNA molecule that carries genes for transposition and thus can move around the genome, or from one genome to another (e.g. from plasmid to chromosome) via recombination