Antibacterial activity and mechanism of recombinant human-defensin 5 against clinical antibiotic-resistant strains


A. P. Wang, Y. P. Su, S. Wang, M. Q. Shen, F. Chen, M. Chen, X. Z. Ran, T. M. Chen and J. P. Wang*

The increasing clinical bacterial strains resistant to conventional antibiotics have being a great challenge to the public’s health. As a novel kind of antimicrobial agent, defensins are undoubtedly worthy of exploitation for the treatment of antibiotic-resistant bacteria. To evaluate the antibacterial potency of recombinant mature human -defensin 5 (rmHD5) against clinical pathogenic strains, we examined its antibacterial kinetics and bactericidal efficacy on forty-nine bacterial strains (belonging to eleven species) with different antibiotic-resistant phenotypes, isolated from digestive and urogenital tracts of the inpatient. Meanwhile, the action mechanism of rmHD5 was analyzed by transmission electron microscopy observation and membrane permeability detection. The peptide of rmHD5 was found to possess high potency against all the tested isolates at concentrations of 6 - 12 g/ml for gramnegative (G- ) bacteria and 28 - 32 g/ml for gram-positive (G+ ) bacteria. Gbacteria were more susceptible to the peptide than G+ bacteria. Abnormal morphological changes and increased permeabilization of the cytomembrane were observed in both G - bacteria and G+ bacteria treated with rmHD5. The antibacterial activity of rmHD5 may be tightly associated with the biomembrane permeabilization. Recombinant mHD5 is a promising candidate to be developed into therapeutic agents for bacterial infections.

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