Mechanism of Antibacterial Activity of <i>Bacillus amyloliquefaciens</i> C‐1 Lipopeptide toward Anaerobic <i>Clostridium difficile</i>

Abstract

Probiotics may offer an attractive alternative for standard antibiotic therapy to treat <i>Clostridium difficile</i> infections (CDI). In this study, the antibacterial mechanism <i>in vitro</i> of newly isolated <i>B. amyloliquefaciens</i> C-1 against <i>C. difficile</i> was investigated. The lipopeptides surfactin, iturin, and fengycin produced by C-1 strongly inhibited <i>C. difficile</i> growth and viability. Systematic research of the bacteriostatic mechanism showed that the C-1 lipopeptides damage the integrity of the <i>C. difficile</i> cell wall and cell membrane. In addition, the lipopeptide binds to <i>C. difficile</i> genomic DNA, leading to cell death. Genome resequencing revealed many important antimicrobial compound-encoding clusters, including six nonribosomal peptides (surfactins (srfABCD), iturins (ituABCD), fengycins (fenABCDE), bacillibactin (bmyABC), teichuronic, and bacilysin) and three polyketides (bacillaene (baeEDLMNJRS), difficidin (difABCDEFGHIJ), and macrolactin (mlnABCDEFGHI)). In addition, there were other beneficial genes, such as phospholipase and seven siderophore biosynthesis gene clusters, which may contribute synergistically to the antibacterial activity of <i>B</i>. <i>amyloliquefaciens</i> C-1. We suggest that proper application of antimicrobial peptides may be effective in <i>C</i>. <i>difficile</i> control.