Abstract
Probiotics may offer an attractive alternative for standard antibiotic therapy to treat Clostridium difficile infections (CDI). In this study, the antibacterial mechanism in vitro of newly isolated B. amyloliquefaciens C-1 against C. difficile was investigated. The lipopeptides surfactin, iturin, and fengycin produced by C-1 strongly inhibited C. difficile growth and viability. Systematic research of the bacteriostatic mechanism showed that the C-1 lipopeptides damage the integrity of the C. difficile cell wall and cell membrane. In addition, the lipopeptide binds to C. difficile 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 B. amyloliquefaciens C-1. We suggest that proper application of antimicrobial peptides may be effective in C. difficile control.
Highlights
Clostridium difficile is an anaerobic, gram-positive, sporeforming bacterium
We focused on the lipopeptide-producing B. amyloliquefaciens strain C-1
Three spots were observed by thin-layer chromatography, and three component peaks were detected by RP-HPLC
Summary
Clostridium difficile is an anaerobic, gram-positive, sporeforming bacterium. Clinical signs of C. difficile infection (CDI) range from mild diarrhea to fulminant colitis [1]. The incidence and severity of CDI have increased significantly, especially by the recently emerged and highly virulent epidemic strain BI/NAP1/027 [2]. With increasing antibiotic resistance of C. difficile, there is an urgent need to develop new agents and efficient methods for the treatment and control of CDI [1, 3]. Distinct from the traditional antibiotics, many novel antimicrobial agents, such as ramoplanin, surotomycin, and cadazolid, are currently being investigated in clinical trials for the treatment of CDI. Surotomycin is an orally dosed lipopeptide antibiotic that acts by disrupting the cell membrane [4]
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