Week 1: Antibiotic Resistance Flashcards
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

Structure of GP vs GN bacteria

Structure of GN bacteria

Structure of GN bacteria

Mechanisms of enzymatic degradation of β-lactams
β-lactams
- β-lactamases
- Classical enzymes
- Extened spectrum β-lactamase
- AmpC
- Carbapenemases
- Metallo-enzymes
Aminoglycosides
- Acetylase
ESBL AKA
Extended spectrum β-lactamase
Extended spectrum β-lactamase

Carbapenem-resistant Enterobacteriaceae

Alterations of ribosomal targets

Alterations of ribosomal targets D-tests

Clindamycin D-test

Alterations of ribosomal targets specifically for aminoglycosides
Mutation in 30S ribosomal subunit (ie streptomycin)
Alterations of ribosomal targets specifically for Linezolid
- G2576T mutation in domain V of 23S rRNA gene
- Can possibly revert back after removal of antimicroial pressure
Alterations of ribosomal targets specifically for DNA Gyrase

Alterations of ribosomal targets specifically for Dihydropteroate synthetase

Mechanisms of Quinolone Resistance

Mechanisms of Aminoglycosides Resistance

What is the MIC?

Question

How are breakpoints set?

Susceptibility report

Blood concentration of drugs and Staph aureus and Pseudomonas aeruginosa

Antibiotic development vs Antimicrobial resistance

Antibiotic drug-discovery

12 steps to prevent antimicrobial resistance in hospitalized adults

How to balance the antimicrobial impact

Practice Antimicrobial control

Antibiotic selection pressure of macrolides

Inappropriate antibitoic prescribing

How much antimicrobial use is either unnecessary or inappropriate

PRevent transmission, isolate the pathogen

U.S. restricts more antibiotics for livestock

What percentage of antibiotics are given to animals vs humans?

Vet antibiotics

GN isolates

GP isolates
