Abstract
Antimicrobial peptides (AMPs) show high antibacterial activity against pathogens, which makes them potential new therapeutics to prevent and cure diseases. Porcine beta defensin 2 (pBD2) is a newly discovered AMP and has shown antibacterial activity against different bacterial species including multi-resistant bacteria. In this study, the functional mechanism of pBD2 antibacterial activity against Staphylococcus aureus was investigated. After S. aureus cells were incubated with different concentrations of pBD2, the morphological changes in S. aureus and locations of pBD2 were detected by electron microscopy. The differentially expressed genes (DEGs) were also analyzed. The results showed that the bacterial membranes were broken, bulging, and perforated after treatment with pBD2; pBD2 was mainly located on the membranes, and some entered the cytoplasm. Furthermore, 31 DEGs were detected and confirmed by quantitative real-time PCR (qRT-PCR). The known functional DEGs were associated with transmembrane transport, transport of inheritable information, and other metabolic processes. Our data suggest that pBD2 might have multiple modes of action, and the main mechanism by which pBD2 kills S. aureus is the destruction of the membrane and interaction with DNA. The results imply that pBD2 is an effective bactericide for S. aureus, and deserves further study as a new therapeutic substance against S. aureus.
Highlights
Defensins are a family of antimicrobial peptides (AMPs) secreted by organisms
It was surprising that purified recombinant Porcine beta defensin 2 (pBD2) had the same strong bactericidal ability, and antibacterial activity increased with pBD2 concentrations (p < 0.01), which is consistent with the results of experiments using the
The bacterial biomass collected after treatment with higher pBD2 concentrations was lower compared with those at lower concentrations, and the debris in the total observed field of view was more visible at higher pBD2 concentrations, which indicates that cells were dead
Summary
Defensins are a family of antimicrobial peptides (AMPs) secreted by organisms. They have high biological activity against bacteria, fungi, and viruses, which makes them alternatives as novel therapeutic drugs [1,2,3]. Only beta defensins have been found, and all beta defensins have been discovered through genomic analysis, except for porcine beta defensin 1 (pBD1). PBD1 is the first beta defensin discovered in pigs, and it has lower bactericidal activity compared with pBD2, which has strong antibacterial activity against both Gram-negative and Gram-positive bacteria including multi-resistant bacteria [6,7,8]. PBD2 has perhaps the strongest antimicrobial activity known among pBDs [6,9,10]. Oral administration of pBD2 reduces the inflammatory response in weaned piglets infected with E. coli [11], and pBD2 attenuates inflammation and mucosal lesions in dextran sodium sulfate-induced colitis in mice [12]
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