Antibiotic Resistance Mechanisms Flashcards
Antimicrobial resistance is
Resistance of a microbe to a drug that was originally effective for treatment of infections caused by it
Resistance is measured by
The increase in the Minimum Inhibitory Concentration of a drug (MIC)
MIC
Minimum Inhibitory Concentration
The lowest concentration of an antimicrobial drug that will inhibit visible growth after overnight incubation
MBC
Minimum Bacteriocidal Concentration
The lowest concentration of an antimicrobial that kills in vitro
A breakpoint is
A chosen concentration of an antibiotic that defines whether a species is susceptible or resistant to an antibiotic
MIC less than or equal to the breakpoint
Bacteria susceptible to the AB
MIC greater than the breakpoint
Bacteria resistant to the AB
A bacteriostatic agent
Reaches MIC levels in the blood/tissues
A bacteriocidal agent
Reaches CIDAL levels in the blood/tissues
A broad spectrum agent
Has low MICs for many different bacterial types
A narrow spectrum agent
Has low MICs for only a few bacterial types
A sensitive (susceptible) microbe
Is inhibited by an agent at a low MIC
A resistant microbe
Is inhibited by an agent only at high MIC
Neisseria Gonhorrheae
Resistant to 3rd generation cephalosporins
Drug inactivation
- Enzymes that modify the drug
e. g. chloramphenicol acetyl transferase - Enzymes that inactivate the drug
e. g. beta lactamases break down the lactam ring - Alteration of drug target site
e. g. ribosomal mutation stops streptomycin binding - Drug efflux pumps
- Modification of membrane permeability
3rd generation cephalosporins
Modify the R groups of the beta lactam ring to increase permeability to interrupt peptidoglycan biosynthesis
Beta lactamase genes
Are found mostly on plasmids
Staph aureus is resistant to penicillin because
Of the presence of a penicillinase
Transpeptidase is also called
A penicillin binding protein (inhibited by penicillin)
S. aureus is resistant to methicillin because
It has a penicillin binding protein encoded by mecA with a lower binding affinity for the beta lactams
MecA is
A variant penicillin binding protein in S. aureus with a lower affinity for beta lactams, resulting in resistance to virtually all beta lactam antibiotics
Staph cassette chromosome mec elements are
Mobile genetic elements
PBP
Penicillin binding protein
Aminoglycosides
Protein synthesis inhibitors
Target 30S subunit
Produced by Streptomyces
Phosphotransferase stops streptomyces killing itself
Encoded by streptomyces phosphorylates OH group so the streptomycin is inactivated
Mutations in the gene encoding the ribosomal protein S12
is another resistance mechanism in Streptomycin resistance
Chloramphenicol is a
Synthetic AB
Chloramphenicol targets the
50S subunit
Protein synthesis inhibitor
Chloramphenicol is inactivated by
Acetylation of two hydroxyl groups
The enzyme that modifies chloramphenicol is called
Chloramphenicolacetyltransferase
Chromosomally encoded cmlA
A gene that causes resistance to choramphenicol by producing more OmpA that leads to reduced membrane permeability
OmpA
Outer membrane porin
Mutations in the 50S subunit genes
Are rare
Drug efflux pumps are present in
All Gram negative and Positive bacteria except RND family
TolC is an
Outer membrane transporter protein found in Gram negative bacteria
In E coli Acr-AB-TolC can extrude
Chloramphenicol, Fluoroquinolone, Tetracycline, Novobiocin and beta lactams
AcrA is a
Membrane fusion protein
AcrAB-TolC is a
Efflux Tripartite system in gram negatives
Many efflux systems can pair up with
AcrAB
The main mediator of resistance to tetracyclines are
Drug efflux pumps
Tetracyclines target the
30S subunit
Protein synthesis inhibitor
Drug efflux genes for tetracyclines are normally based on
Plasmids
R plasmids can be up to a
100Kb
so can have up to 100 genes on them - quite a lot
R plasmids can encode for
More than one resistance mechanism
Transposons are
‘Jumping genes’
Mobile genetic elements that jump in and out of chromosomes
Can also be found on plasmids
Transposons often contain
Antibiotic resistance genes
Resistance genes can be transferred by
Vertical OR Horizontal gene transfer
Antibiotics provide
Selection pressure
Consequence is evolution and spread of resistance genes
The main cause of the spread of AB resistance is
Horizontal gene transfer
Horizontal gene transfer is
Rapid, spreads between cells without needing the presence of antibiotic
Three mechanisms of horizontal gene transfer
- Transformation
- Transduction
- Conjugation
Competent bacteria
Take up DNA naturally
Transformation is
Uptake of foreign DNA
Transduction is
Using phage to transfer genetic material from one bacterium to another
Conjugation is
Transfer of a plasmid through an F pilus. The donor bacterium needs a DNA sequence called the fertility factor, or F-factor.
Transformation is mediated by
Competence proteins
Competence proteins
Pull in and unwind DNA
Same proteins that are involved in Type 4 secretion systems
Found in G+ and G- bacteria
