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The synergistic antimicrobial effects of novel bombinin and bombinin H peptides from the skin secretion of Bombina orientalis
Bombinin and bombinin H are two antimicrobial peptide (AMP) families initially discovered from the skin secretion of Bombina that share the same biosynthetic precursor-encoding cDNAs, but have different structures and physicochemical properties. Insight into their possible existing relationship lead...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Portland Press Ltd.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5634238/ https://www.ncbi.nlm.nih.gov/pubmed/28894024 http://dx.doi.org/10.1042/BSR20170967 |
Sumario: | Bombinin and bombinin H are two antimicrobial peptide (AMP) families initially discovered from the skin secretion of Bombina that share the same biosynthetic precursor-encoding cDNAs, but have different structures and physicochemical properties. Insight into their possible existing relationship lead us to perform the combination investigations into their anti-infectious activities. In this work, we report the molecular cloning and functional characterization of two novel AMPs belonging to bombinin and bombinin H families from secretions of Bombina orientalis. Their mature peptides (BHL-bombinin and bombinin HL), coded by single ORF, were chemically synthesized along with an analogue peptide that replaced L-leucine with D-leucine from the second position of the N-terminus (bombinin HD). CD analysis revealed that all of them displayed well-defined α-helical structures in membrane mimicking environments. Furthermore, BHL-bombinin displayed broad-spectrum bactericidal activities on a wide range of microorganisms, while bombinin H only exhibited a mildly bacteriostatic effect on the Gram-positive bacteria Staphylococcus aureus. The combination potency of BHL-bombinin with either bombinin HL or bombinin HD showed the synergistic inhibition activities against S. aureus (fractional inhibitory concentration index (FICI): 0.375). A synergistic effect has also been observed between bombinin H and ampicillin, which was further systematically evaluated and confirmed by in vitro time-killing investigations. Haemolytic and cytotoxic examinations exhibited a highly synergistic selectivity and low cytotoxicity on mammalian cells of these three peptides. Taken together, the discovery of the potent synergistic effect of AMPs in a single biosynthetic precursor with superior functional selectivity provides a promising strategy to combat multidrug-resistant pathogens in clinical therapy. |
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