Antibiotic Resistance Flashcards
List common antimicrobial targets and the classes of antibiotics that target them
- Cell wall synthesis (Penicillins, cephalosporins, glycopeptides- vancomycin)
- Nucleic acid synthesis - fluoroquinolones
- Cell membrane Lipopeptides- Daptomycin
- Nucleotide synthesis (folic acid)- Trimethoprim
- Protein synthesis- Aminoglycosides, tetracyclines, macrolides
Describe the mechanism of action of Beta Lactam antibiotics
B lactam-containing antimicrobials such as the penicillins and cephalosporins inhibit cell wall synthesis.
They bind to transpeptidase enzyme known as penicillin binding protein which is essential for the synthesis of the bacterial peptidoglycan cell wall.
Describe the mechanism of action of fluroquinolones
Act on nucleic acid synthesis
Fluoroquinolones such as ciprofloxacin inhibit DNA replication and transcription.
They bind to the bacterial enzyme DNA gyrase which relives DNA supercoiling and is essential to allow DNA/RNA polymerases to synthesise new nucleic acids.
Describe the mechanism of action of trimethoprim
Act on nucleotide synthesis
Trimethoprim inhibits the enzyme dihydrofolate reductase (DHFR) which is essential for nucleotide synthesis and therefore DNA replication.
List the mechanisms of antibiotic resistance
- Target mutation
- Enzymatic degradation
- Reduced permeability
- Antibiotic efflux
- Alternative metabolic pathways
Describe ‘target mutation’ as a method of antibiotic resistance
Mutation of the gene encoding the target protein. The mutation removes the ability of the antibiotic to bind to the protein but maintains the function the protein has in bacterial metabolism. E.g. the mutated from of DHFR can prevent trimethoprim binding but can still perform the reduction of dihydrofolate necessary for nucleotide synthesis.
Describe enzymatic degradation as a method of antibiotic resistance
Bacteria can produce enzymes that break down or modify the antimicrobial agent, making it ineffective.
E.g. B-lactamases are enzymes that break down the B-lactam ring of penicillins.
B-lactamase inhibitors are drugs that have little antimicrobial activity themselves but can be used to prevent microbial resistance to penicillins.
Describe reduced permeability as a method of antibiotic resistance
The outer cell membrane of Gram negative species contains proteins that form pores, allowing the entry of water-soluble substances including penicillin, aminoglycoside and macrolide antimicrobials.
Loss of expression or mutation of the genes encoding these porins can prevent these antimicrobials from entering the cell and render them ineffective.
Describe antibiotic efflux as a method of antibiotic resistance
Many bacterial species have a range of membrane proteins capable of ejecting antimicrobial agents from the cell.
E.g. Escherichia coli proteins TetB and TolC and the pseudomonas aerugonisoa PmpM.
These systems often use the concentration gradient of H+ across the bacterial cell membrane to provide the energy for antimicrobial efflux.
Describe the ways in which alternative metabolic pathways can be used for antibiotic resistance
The synthesis of physiologically important bacterial substances can sometimes be achieved through alternative biochemical intermediates.
E.g. Peptidoglycan synthesis for bacterial cell walls can be proceeded by a different route in some bacteria resistance to penicillins.
Sometimes the biochemical intermediates are the same, however a different enzyme can be used to catalyse the reactions involved.
Define vertical gene transfer
the passing on of genetic information as part of the process of reproduction. In bacteria, the chromosomal genetic information is replicated prior to cell division.
Allows clonal proliferation of bacterial cells containing antimicrobial resistance genes, particularly when antibiotic use has killed susceptible ‘competing’ cells.
Define horizontal gene transfer
The process of exchanging mobile non-chromosomal genetic material such as plasmids between ‘unrelated’ individual bacterial cells. Allows antimicrobial resistance genes to spread to previously susceptible cells within a bacterial population, including between different species.
Describe the 3 ways in which horizontal gene transfer can occur
- Transformation: the uptake of short DNA fragments from the surrounding medium without direct cell-cell contact.
- Transduction: where DNA is transferred from one bacterial cell to another by bacteriophage, viruses that can infect bacteria.
- Conjugation: involves transfer of DNA from one bacterium to another by direct cell-cell contact.
- Occurs via a pilus
