3.2 Flashcards
Antibiotic Resistance
First antibiotic used for MRSA & mechanism
Penicillin becomes available, targets transpeptidase
* beta-lactamase destroy penicillin so staph infections are resistant
Second antibiotic used for MRSA & mechanism
Methicillin –> resistant to beta-lactamases
* BUT mutation is discovered in transpeptidase
Third antibiotic used for MRSA & mechanism
Vancomycin –> target both transpeptidase and trans glycosylase
* BUT vancomycin is big and bulky, so resistance developed through thickening cell wall
Fourth antibiotic used for MRSA & mechanism
Linezolid –> targets ribosomes
* BUT found efflux pump that pumped it out
Daptomycin
targets G+ cell membrane, effective against MRSA
- BUT Daptomycin resistant S. aureus observed
Ceftaroline
beta-lactam that inhibits gene found in MRSA
- BUT resistance was detected due to mutations found
What have we learned now?
Seeing dangerous combinations of resistance in strains known as MDR-MRSA
Mechanisms of how bacteria become resistant
- Alter ability of drug to get there (core, glycocalyx, cell envelope)
- Altering drug target (Methicillin)
- Pump drug out (Linezolid)
- Enzyme that destroys drug (Beta-lactamase)
How have bacteria evolved resistance to antibiotics?
- Mutations
- pressure placed –> will change and evolve
- “survival of the fittest” –> pressure: starvation state, high temps; kill weakest bacteria first
- humans are artificially providing pressure - DNA transfer and genetic recombination
a. Transformation
b. Transduction
c. Conjugation
Transformation
Uptake of DNA directly from its surroundings
- when bacteria lyse, all genetic material is released
- living cells open up and take DNA when it feels pressure –> most times it doesn’t work
- last effort
Transduction
Transfer of DNA between bacteria via bacteriophage
- total accident, involves virus
Conjugation
Transfer of R plasmid via direct contact
- intentional
- artificially select for resistant population
- Resistant bacteria can give this plasmid to their sister cells, esp when exposed to selective pressure
Plasmid Promiscuity
Bacteria combine beneficial genes from multiple plasmids together (R plasmid that provides resistance to numerous antibiotics)
AND they also share these plasmids, they are not limited by species
Early TEM-1, SHV-1
resistance to penicillin
CTX-M/ESBL
considered an ESBL; all beta-lactams except carbapenem
KPC
resistance to carbapenem
NDM
resistant to ALL beta-lactams
Mcr-1
resistance to colistin (polymyxins)
six causes of antibiotic resistance
- over-prescribing antibiotics
- patients not finishing their treatment
- over-use of antibiotics in livestock and fish farming
- poor infection control in hospitals and clinics
- lack of hygiene and sanitation
- lack of new antibiotics being developed
Later SHV/TEM
all beta-lactams except carbapenem
