Week 1: Antibiotic Resistance Flashcards
(60 cards)
Objectives
Mechanisms of bacterial antibiotic resistance
- Point mutations (micro-evolutionary)
- Macro-evolutionary change
- Acquisition of foreign DNA
Describe point mutations as it pertains to bacterial antibiotic resistance
- micro-evolutionary
- may occur in a nucleotide base pair
- ESBL (Extended spectrum beta lactamases) are examples of point mutation that occured on classical enzymes
Describe macro-evolutionary change as it pertains to bacterial antibiotic resistance
- Whole-scale rearrangements of large segments of DNA as a single-event
- May include: inversions, duplications, insertions, deletions or transposition of large sequences of DNA from one location of a bacterial chromosome or plasmid to another
- Created by genetic elements known as ‘Transposons’
Describe Acquisition of foreign DNA as it pertains to bacterial antibiotic resistance
Carried by plasmids, bacteriophages or transposable genetic elements
What % of bacterial resistance arises from de novo mutations
small % of resistance evolution
What % of bacterial resistance arises from acquisition?
Is most common form of developing antibiotic resistance
How is genetic material transfered?
Transfer of genetic material coding for resistance is plasmid (P) or transposon (T) mediated
What are plasmids?
Plasmids are extrachromosomal pieces of DNA that replicate within bacterial cell but limited in transfer between classes
What are transposons?
Transposons are extrachromosomal pieces of DNA that are not limited but generally must be attached to chromosome, bacteriophage or plasmid for replication
Mechanisms of horizontal gene transfer
What is intrinsic resistance?
How does intrinsic resistance occur?
4 listed
Can be due to
- Lack of affinity of the drug for the bacterial target
- Inaccessibility of the drug into the bacterial cell
- Extrusion of the drug by chromosomally encoded active exporters
- Innate production of enzymes that inactivate the drug
Examples of intrinsic resistance
3 listec
- Vancomycin against gram-negative organisms
- Cephalosporins against Enterococci
- Metronidaole against aerobic bacteria
Bacterial employed mechanisms of resistance
- enzymatic degradation of the antibiotic agents
- Alterations of the targets of antibiotic agents
- Changes in cell wall permeability and/or production of efflux pumps
Examples of Resistance: Alteration to Penicillin Binding proteins
- β-lactams (Enterococci, Streptococci, Staphylococci)
Examples of Resistance: Modified cell wall precursors (ie D-ala-D-ala to D-ala-D-lac)
Vancomycin (Enterococci, Staphylococci)
Examples of Resistance: Alteration to of ribosomal targets
- Aminoglycosides
- macrolides
- Lincosamides
- Linzolid
- Tetracyclines
- Tigecycline
Examples of Resistance: Alteration in target enzymes
- Quinolones
- TMP/SMX
Examples of Resistance: Efflux TetA gene
- Tetracycline resistance in S. aureus
- Streptococci
- Enterobacteriaceae
Examples of Resistance: Cleave
β-lactamase destroy the β-lactam ring of PCNs, cephalosporins, Carbapenems (S. aureus, Pseudomonas, Enterobacteriaceae)
Examples of Resistance: Porin channel alteration
- Carbapenem and quinolones in Pseudomonas
Describe the mechanism of Enterococcal resistance to Vancomycin
Describe VanA from VRE to S. aureus
