Antibacterials & Antibiotics Flashcards
What does antibacterial mean?
A substance that kills bacteria or inhibits bacterial growth
What is an antibiotic?
A substance produced by a living organism that is capable of destroying or inhibiting the growth of microorganisms
What is an antimicrobial?
A substance that kills microorganisms or inhibits their growth
Where do antibiotics come from in nature and why do they work?
Mainly from soil, are secreted to kill or slow competitors
How does clinical resistance form?
When resistance genes are mobilised and moved as a consequence of genetic transfer to organisms that cause infections
What does bactericidal mean?
Antibiotics that kill bacteria, but at low concentrations can be bacteriostatic
What does bacteriostatic mean?
Slow bacterial growth without killing them, but at high concentrations can be bactericidal
Main points of cell wall synthesis inhibitors
- more effective against gram +ve
- disrupt bacterial maintenance of osmotic pressure
- selective, as there is no cell wall in mammals
- generally bactericidal
What are beta-lactams and how do they work?
Drugs that target cell components within the cell wall and destroy integrity
How does Fosfomycin work?
Inhibits phosphoenolpyruvate which is essential for peptioglycan synthesis, limiting the conversion of NAG to NAM and the cross linking between them
How does cycloserine work?
- is an analog of D-Ala, which prevents activity of enzymes (alanine racemase) involved in peptidoglycan synthesis
- alanine racemase cannot convert L-Ala into D-Ala, so peptidoglycan synthesis is inhibited
How does bacitracin work?
Interferes with isoprenylphosphate which carries and transports peptidoglycan molecules, meaning the cell wall can’t be build
How does Vancomycin and Teicoplanin work?
Pretends to be D-Ala-D-Ala in gram +ve bacteria, replacing the residue in the NAM-NAG peptide, stopping peptidoglycan being produced
How is synthetic penicillin made?
- stripping side chains from natural penicillin and adding new ones
- stopping penicillin synthesis early and purifying the central B-lactam ring core
How does Rifampicin work?
- it interferes with the RNA polymerase/DNA complex, preventing separation of the DNA strands and inhibiting transcription
What is Rifampicin?
It is an RNA synthesis inhibitor, which targets the DNA dependent RNA synthesis pathway which uses different RNA polymerases to humans
What are fluoroquinalones?
DNA synthesis inhibitor with low MIC, which target enzymes in bacteria similar to humans
How do fluoroquinalones work?
- Inhibit Topoisomerase 2&4 which are critical for DNA replication
- Gyrase bind DNA and hold the strands in place, quinoline arrests the DNA/gyrase complex so DNA can’t be repaired and released
What is Metronizadole?
A DNA synthesis inhibitor which is selectively absorbed by anaerobic bacteria
What does Metronizadole do?
Once activated in area of anaerobiosis, the formation of unstable intermediates interact with bacterial DNA and poke holes
Benefits of antibiotic combinations
- delays emergence of resistance
- synergy between the 2 drugs
- act in sequential steps in the pathway
- bactericidal in combination
How does Colistin work?
Interacts and disrupts the plasma membrane of gram -ve bacteria
How does 2 complement system of coliston work?
Sense antibiotic on surface, and trigger changes through a regulator, alter production and presentation of LPS on the microbe surface
How do beta lactamases work?
- beta lactam antibiotic diffuses through porins of the outer membrane and enter periplasmic space
- beta lactamases degrade the antibiotic
What does penicillin binding protein do?
- if any antibiotic passed through the beta lactamase system, pbp interacts with the molecules and inhibits them
What is vertical acquisition?
When a species acquires a plasmid which spreads, causing cross infection between patients in a specific environment
What is horizontal acquisition?
A plasmid spreads into diverse species ubiquitously and continues spreading
What are extended spectrum beta lactamases?
Beta lactamases which can degrade 3rd generation cephelasporins like cefotaxime and ceftazidine
What are the 4 types of beta lactams?
Penicillins, cephelasporins, carbapenems, and monobactams
How do beta- lactamases work against amoxicillin?
Cleaves the amide ring in penicillin/beta lactam molecule, flipping the conformation and making it useless
How does the TEM-1 beta lactamase work?
Small amoxicillin molecules enter and bind directly with the ser70 active site, which cleaves the amide ring and renders it impotent
What antibiotics does TEM-1 not work against and why?
Cephelasporins, as they are too large of a molecule to fit into the ser70 binding site
What antibiotics does TEM-1 not work against and why?
Cephalosporins, as the molecules are too large to fit in the Ser70 active site
How does dual resistance to fluoroquinalones and cephalosporin arise?
- plasmid resistant to both
- expansion of a strain with chromosomal mutation for quinalone resistance and contains a plasmid encoding beta lactamase
The process of plasmid genes inserting into bacterial genome?
Plasmids carry integrons, which can insert into transposon, which can be inserted into a different plasmid. The integron and transposon can excise themselves from the plasmid and insert into chromosome.
What is OmpC?
Is a porin that aids permeability of carbapenem, when it is absent the drug is not fast enough to act on the bug
What are transposons?
Jumping genes that can move into a chromosome OR into another plasmid in the strain
What is conservative transposition?
- cut & paste method -
Transposon from donor is excised, then inserted into the recipient, mediated by transposase
What is replicative transposition?
- copy & paste
- DNA synthesis happens from open ends via DNA polymerase
- tnpA causes ligation at nicked ends
- cointegrate has 2 copies of the transposon. 1 copy is resolved through tnpR to stay within donor, while second moves on to target replicon
