Antibiotic Resistance
The ability of bacteria to survive exposure to antibiotics that would normally kill or inhibit them. Rising antibiotic resistance is a global health crisis. Peptide-based antibiotics (vancomycin, daptomycin, colistin, polymyxin B) remain critical last-resort treatments. Novel antimicrobial peptide development is an active research area.
Technical Context
Resistance mechanisms relevant to peptide antibiotics: glycopeptide resistance — vanA/vanB gene clusters encode enzymes that modify the D-Ala-D-Ala peptidoglycan target to D-Ala-D-Lac (1000-fold reduced vancomycin binding) in VRE (vancomycin-resistant Enterococci) and rare VRSA (vancomycin-resistant S. aureus); polymyxin resistance — mcr genes encode phosphoethanolamine transferases that modify lipid A, reducing the anionic charge that polymyxins exploit for membrane binding (plasmid-mediated, transferable between species — a major global concern); daptomycin resistance — mutations in mprF and other genes alter membrane phospholipid composition, reducing daptomycin binding; and echinocandin resistance — FKS gene mutations alter the beta-1,3-glucan synthase target (relevant to rezafungin). The WHO's priority pathogen list highlights organisms where antibiotic resistance poses the greatest threat — several require peptide antibiotics as last-resort treatments. Novel antimicrobial peptide development (engineered AMPs, lantibiotics, peptide-antibiotic conjugates) aims to address the growing resistance crisis.