Antibiotic resistance Flashcards
What is primary drug resistance?
When the microorganism is naturally resistant to the substance.
What is secondary drug resistance?
When the microorganism becomes resistant after exposure- usually caused by a genetic mechanism
Name 4 mechanisms of antibiotic resistance.
- Drug inactivation
- Alteration in drug target
- Drug penetration barrier
- Drug efflux
Describe drug inactivation.
Beta lactamase enzyme destroys the beta lactam portion of the antibiotic, thus making it inactive. Beta lactamase is very active and this occurs quickly.
Chloramphenicol acetyltransferase adds an acetyl group to the drug, thus inactivating it (it doesn’t bind to the ribosome anymore)
Describe alteration in drug target. (3 types)
- Mutated DNA gyrase -> quinalones resistance
- Adenine methylase methylates. 23sRNA -> erythromycin resistance
- Mutated penicillin binding proteins in cell wall -> penicillin resistance
Describe Drug penetration barrier (barrier to entry)
Loss/reduction of drug receptors eg loss of porins -> carbapenems resistance
Describe drug efflux.
Efflux pumps are membrane proteins that actively pump out antibacterials (tetracyclines) or antifungals ( fluconazole) out of the cell.
What are three genetic mechanisms of antibiotic resistance?
- Chromosomal mutations
- Horizontal gene transfer
- Regulating gene expression
CHR (chur)
Describe chromosomal mutations.
Point mutations: Single base changes which may result in changed or inactive proteins
Frameshift mutations: Insertions/deletions which result in inactive proteins.
Describe ‘regulating gene expression’
Switching genes on/off- related to mutations.
What is horizontal gene transfer?
The process by which an organism incorporates genetic material from a donor organism without being the offspring of the donor organism.
- Uptake/transfer of plasmids
- Uptake of chromosomal DNA from lysed cells
Define plasmid.
An extrachromosomal genetic entity. These replicate independently of the chromosome (selfish). Many encode their own conjugative transfer. Cells can have multiple plasmid types.
Under what circumstances may plasmids be essential? (6)
- Antibiotic resistance
- Virulence factors
- Heavy metal resistance
- Toxins or antimicrobial proteins
- Cell surface structures
- New metabolic pathways
Define horizontal gene transfer.
The process by which an organism incorporates genetic material from another organism (the donor) without being the offspring of the donor organism.
What are the three mechanisms of horizontal gene transfer?
- Transduction
- Transformation
- Conjugation
What do all mechanisms of horizontal gene transfer involve?
Genetic recombination- rearrangement of DNA by breaking and rejoining homologous sequences- may result in phenotypic change.
What are bacteriophages?
Viruses that specifically infect bacteria (the ultimate parasites)
- no metabolic or synthetic capabilities
- Relies totally on the host cell
- Genome DNA OR RNA based
- Genome contains 3-135 genes
What are the two types of bacteriophage?
- Litic (virulent)
- Temperate
Describe lytic bacteriophages.
Enter cell, replicates, cell bursts, viral particles released to surroundings.
Describe temperate bacteriophages.
Enters cell, remains in dormant state (integrates phage genome into bacterial chromosome) until activated by UV light or something- becomes lytic.
What is transduction?
Virus (bacteriophage) mediated genetic recombination
What is transformation?
Uptake of free DNA by competent cells ie in saliva released by cells when they lyse. DNA may be recombined into genome and expressed.
What is conjugation?
Bacterial sex between closely related strains/species. Cell to cell DNA transfer through a sex pilus (direct contact). This is mediated by specific genes found on conjugative plasmids or transponsons.
What may plasmids carry?
Antibiotic resistance and/or conjugative genes
Describe insertion sequences, transposons, integrons.
- Mobile genetic elements within the genome (chromosome or plasmid)
- Can carry antibiotic resistance genes
- Can jump to other species by conjugation (pilus)
