Abstract
In this study, we designed and synthesized three N-terminal deletion analogs of human beta-defensin 3 (hBD-3), namely, hBD-3Δ4, hBD-3Δ7, and hBD-3Δ10, to determine the effect of N-terminal residues on the antibacterial activity and salt resistance of these peptides. The antibacterial activities and salt resistance of hBD-3 and its analogs were tested against a broad range of standard and clinically isolated strains. The deletion of nine N-terminal residues significantly reduced the antibacterial activity of hBD-3 against most of tested strains, particularly Klebsiella pneumonia. Compared with hBD-3 and other analogs, the analog with a deletion of three residues, hBD-3Δ4, exhibited significantly higher antimicrobial activity against almost all the tested strains, especially Escherichia coli and Enterococcus faecium, at high NaCl concentrations. Given its broad spectrum of antimicrobial activity and high salt resistance, hBD-3Δ4 could serve as a promising template for new therapeutic antimicrobial agents.
Highlights
Human defensins, which are rich in cationic amino acids and cysteine residues, are crucial components of the innate immunity of humans [1, 2]
Ten strains obtained from the American Type Culture Collection (ATCC) and China Center of Industrial Culture Collection (CICC) were used for antibacterial and salt resistance assays
Aeruginosa, K. pneumonia, and S. aureus, but only below 15% CFU of E. coli, S. flexneri, and S. sonnei. hBD-3Δ10 showed the same salt resistance as hBD3Δ7 in all tested strains but exhibited significantly weaker antibacterial activity at high NaCl concentrations (Fig. 1D)
Summary
Human defensins, which are rich in cationic amino acids and cysteine residues, are crucial components of the innate immunity of humans [1, 2]. The broad antibacterial spectrum and high antibacterial activity of human defensins make them important effector molecules of mucosal surface, skin, and epithelia [3]. Human beta-defensins 1 to 4 (hBD-1 to hBD-4) exert different bactericidal activities against various pathogens [1,2,3]. Compared with hBD-1 [6], hBD-2 [7], and hBD-4 [8], human betadefensin 3 can withstand higher NaCl concentrations because of its irregular structural characteristics and charge [9]. HBD-3 is a 45-residue cationic peptide with an asymmetrical distribution of charged residues clustered mostly at the carboxyl-terminal (C-terminal) region [10]. The nuclear magnetic resonance solution structure of hBD-3 shows three anti-parallel betasheets and a short helical loop at the N-terminal region [11]. The 3D structure of hBD-3 is PLOS ONE | DOI:10.1371/journal.pone.0117913 February 23, 2015
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