Antibiotics And Antibiotic Resistance Flashcards
What is an antibiotic ?
A compound produced by one organism to kill or inhibit the growth of another specific organism
Characteristics of an ideal antibiotic agent
- Readily available
- Inexpensive
- Chemically stable
- Easily administered
- Non toxic and non allergic
- Selectively toxic against wide range of pathogens
Mechanisms of Antibiotic Action
- Selective toxicity — attack bacteria, not us
- Few drugs to treat eukaryotic infections
- Even fewer antiviral drugs
Antibiotic targets
- Cell wall synthesis - B-lactams (beta)
- Protein synthesis - Tetracycline
- DNA transcription and translation - Quinolones
Inhibition of cell wall synthesis - penicillin
- Only works on dividing cells
- Least toxic of antibiotics
- Resistance to penicillin widespread
- Penicillin V oral, G injection
- Ampicillin - semi-synthetic - broader spectrum
Mechanisms of action of penicillins
- Penicillin binds to penicillin binding protein (pbp)
- Role of pbp is to make cross-links in peptidoglycan
- Penicillin binds to pbp and deactivates it
- Peptidoglycan has no cross links = fragile
The penicillin antibiotic family
- Natural - penicillin G, penicillin V
- Anti-staphylococcal - methicillin, oxacillin, nafcillin
- Extended spectrum - ampicillin, amoxicillin, carbenicillin
- Beta-lactamse inhibitor - clavulanic acid, sulbactam, tazobactam
Inhibition of protein synthesis - Tetracycline
- Inhibits protein synthesis in the ribosome
- Binds to 30S subunit
- Stops protein synthesis by preventing the tRNA binding to the mRNA
Inhibition of DNA replication
- A number of antibiotic families inhibit the process of DNA replication
- Focus is on quinolones
- Stabilisation of topoisomerases — cut DNA strands to start replication
- DNA is broken
Quinolones
- Quinolones stabilise the topoisomerase-DNA cleavage complex = double-strand break
- If the cleavage complex isn’t resolved = no replication & no transcription = slow bacterial cell death
- If topoisomerase is removed = double strand break is free
- If double strand is left unrepaired = fragmentation of the chromosomes = rapid bacterial cell death
- Stabilised cleavage complex / removal of topoisomerase from the cleavage complex = accumulation of reactive oxygen species (ROS) = rapid bacterial cell death;
Spectrum of action
- Not all antibiotics work for all bacteria so the ones that = spectrum of action
- Broad spectrum
- Broad spectrum anti microbial may allow secondary infections to develop
- Killing of normal flora - overgrowth with resistant organisms
How antibiotic resistance happens
- Lots of germs. A few are drug resistant
- Antibiotics kill bacteria causing the illness as well as good bacteria protecting the body from infection
- The drug-resistant bacteria are now allowed to grow and take over
- Some bacteria give their drug resistance to their bacteria = more problems
Evolution of antibiotic resistance - overuse
- When antibiotics is prescribed for viruses that they can’t kill (e.g, common cold)
= destruction of normal flora
- Opportunistic pathogens that are resistant survive
Evolution of antibiotic resistance - hospitals
- High concentrations of organisms which are extremely pathogenic
- Large amounts of different antibiotics are constantly in use
- Increased use of antibiotics = resistance
Mechanisms of antibiotic resistance
- Alteration of target site
- Efflux
- Inactivation of antibiotic
- Reduced permeability
Alteration of target site
- Mutations changes target site
- Rendering antibiotic powerless
E.g, Alteration of Penicillin Binding Proteins (PBP)
Efflux pumps
Problematic/ found in outer membranes Gram-negatives
Main role = pump out waste and other noxious chemicals
Over-expression = resistance
Antibiotic inactivation
A) Inactivation by hydrolysis
B) Inactivation by modification
Decreased uptake
New porin channels in the bacterial cell do not allow antibiotics to enter the cells
How to stop resistance from developing
- High concentrations of drug maintained in patient for long enough time
- Use of antimicrobial agents in combination
- Limited use of microbial to necessary cases
- Development of new variations of existing drugs — 2nd and 3rd gen drugs
New antimicrobials
Natural antibacterial compounds
- Bacteria based - bacteriocins
- Plant based - flavonoids, monoterpenes
- Animal based - chitosan, renalexin
Old medications, new uses
- Antipsychotic thioridazine
- AZT
- Thalidomide
Bacteriophages
Photodynamic therapy
- Photosensitisers - free radicals and reactive oxygen species
Vaccination
