In vitro bactericidal activity of human beta-defensin 2 against nosocomial strains.
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.
Routsias
John G
JG
Department of Microbiology, School of Medicine, National and Kapodistrian University of Athens, 75 M.Asias St., 11527 Athens, Greece. jroutsias@med.uoa.gr
Karagounis
Panagiotis
P
Parvulesku
Georgeta
G
Legakis
Nikolaos J
NJ
Tsakris
Athanassios
A
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D015169:Colony Count, Microbial; D024901:Drug Resistance, Multiple, Bacterial; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006801:Humans; D020128:Inhibitory Concentration 50; D009994:Osmolar Concentration; D010084:Oxidation-Reduction; D012965:Sodium Chloride; D023083:beta-Defensins / Q000737:chemistry / Q000494:pharmacology*; D018440:beta-Lactam Resistance
D000900:Anti-Bacterial Agents; C106641:DEFB4A protein, human; D023083:beta-Defensins; D012965:Sodium Chloride