Human beta-defensin 2 (hBD-2) is a 41-amino acid cationic peptide of the innate immune system that serves as antimicrobial molecule. We determined the bactericidal activity of synthetic hBD-2 against nosocomial strains belonging to eight different bacterial species and exhibiting various antimicrobial resistance phenotypes. The native disulfide connectivity was found essential for the bactericidal activity of hBD-2, while sodium chloride concentration was reversely associated with its potency. hBD-2 exhibited high bactericidal activity against Acinetobacter baumannii, Pseudomonas aeruginosa, Enterococcus faecalis, Enterococcus faecium and Staphylococcus aureus clinical strains. Characteristically, A. baumannii strains that exhibited multi-drug resistant (MDR) phenotypes were susceptible to lower concentrations of hBD-2 (vLD(90)=3.25-4.5 microg/ml) in comparison with non-MDR (wild-type) A. baumannii strains (vLD(90)=3.90-9.35 microg/ml). Bactericidal activity of hBD-2 was less pronounced against Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis strains but was significantly enhanced against strains of these species that exhibited resistance to several beta-lactam antibiotics. These observations give indications that the natural hBD-2 has a potential therapeutic role against bacterial pathogens and particularly against those exhibiting MDR phenotypes.
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Article Synopsis
- The rise of multidrug-resistant bacteria highlights the urgent need for new antimicrobial medicines, leading to the investigation of antimicrobial peptoids as potential alternatives.
- Thirteen peptoid analogues were synthesized with varying alkyl side chains to analyze their antibacterial properties, and only one, called Tosyl-Octyl-Peptoid (TOP), showed significant broad-spectrum bactericidal activity.
- TOP effectively kills bacteria in both dividing and non-dividing states, demonstrating promising minimum inhibitory concentrations and a high selectivity ratio, suggesting its potential as a future therapeutic option against resistant infections.
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