Antibiotics resistance mechanism

 

  • Bacteria develop ability to hydrolyze these drugs using β lactamase
    • confers resistance to penicillin
    • e.g. E. coli, Staph epidermidis, Pseudomonas aeruginosa, Klebsiella pneumoniae
    • add β lactamase inhibitor e.g. clavulanic acid in amoxicillin-clavulanate (Augmentin)
  • Genetic mutation of mecA
    • carried by Staphylococcal cassette chromosome (SCCmec) mobile genetic unit
    • a bacterial gene encoding a penicillin-binding protein (PBP2a). 
      • PBP2a has reduced affinity for antibiotics
      • confers resistance to methicillin, oxacillin, nafcillin
      • e.g. MRSA
        • SCCmec type IV has less genetic elements and is specific to CA-MRSA, making CA-MRSA less multi-drug resistant
  • Altered cell wall permeability
    • confers resistance to tetracyclines, quinolones, trimethoprim and β lactam antibiotics
  • Creation of biofilm barrier 
    • provides an environment where offending bacteria can multiply safe from the hoste immune system
      • Salmonella
      • Staph epidermidis
  • Active efflux pumps
    • confers resistance to erythromycin and tetracycline
    • e.g. msrA gene in Staph
  • Altered peptidoglycan subunit (altered D-alanyl-D-alanine of NAM/NAG-peptide) 
    • confers resistance to vancomycin
    • e.g. vancomycin resistant enterococcus (VRE) 
  • Ribosome alteration
    • erm gene confer inducible resistance to MLS (macrolide lincosamide streptogranin) agents via methylation of 23s rRNA
    • demonstrate using D zone test 
      • for inducible clindamycin resistance in Staph and beta hemolytic Strep


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