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Strategy 4: Modification of the antimicrobial target.

Some resistant bacteria evade antimicrobials by reprogramming or camouflaging critical target sites to avoid recognition. Therefore, in spite of the presence of an intact and active antimicrobial compound, no subsequent binding or inhibition will take place. 

This strategy has been observed in:

  • Staphylococci against methicillin and other beta-lactams (Changes or acquisition of different PBPs that do not sufficiently bind beta-lactams to inhibit cell wall synthesis.)
  • Enterococci against vancomycin (alteration in cell wall precursor components to decrease binding of vancomycin)
  • Mycobacterium spp. against streptomycin (modification of ribosomal proteins or of 16s rRNA)
  • Mutations in RNA polymerase resulting in resistance to the rifamycins;
  • Mutations in DNA gyrase resulting in resistance to quinolones


Some Examples Of Bacterial Resistance Due To Target Site Modification 4, 18:


  • Alteration in penicillin-binding protein (PBPs) leading to reduced affinity of beta-lactam antibiotics (Methicillin-Resistant Staphylococcus aureus, S. pneumoniae, Neisseria gonorrheae, Group A streptococci, Listeria monocytogenes)
  • Changes in peptidoglycan layer and cell wall thickness resulting to reduced activity of vancomycin: Vancomycin-resistant S. aureus
  • Changes in vancomycin precursors reducing activity of vancomycin: Enterococcus faecium and E. faecalis
  • Alterations in subunits of DNA gyrase reducing activity of fluoroquinolones:
  • Many Gram-negative bacteria
  • Alteration in subunits of topoisomerase IV leading to reduced activity of fluoroquinolones: Many Gram positive bacteria, particularly S.auerus and Streptococcus pneumoniae
  • Changes in RNA polymerase leading to reduced activity of rifampicin: Mycobacterium tuberculosis




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