An Intestinal Bacillus velezensis Isolate Displays Broad-Spectrum Antibacterial Activity and Prevents Infection of Both Gram-Positive and Gram-Negative Pathogens In Vivo

The rise of antibiotic-resistant pathogens poses a challenge to public health. The gut microbiome presents a promising source of new antimicrobials and treatments. The increasing prevalence of drug-resistant bacteria has significantly diminished the effectiveness of antibiotics in clinical settings, leading to the emergence of untreatable bacterial infections. To address this public health challenge, the gut microbiome represents a promising source of novel antimicrobial therapeutics. In this study, we screened mouse intestinal isolates for growth inhibitory activity against the human enteric pathogen Vibrio cholerae and identified a strain of spore-forming Bacillus velezensis, named BVM7, that produced a potent antibiotic with activity against V. cholerae and a broad spectrum of enteric and opportunistic pathogens. Characterization of the antimicrobial compounds produced by BVM7 revealed that they were primarily secreted antimicrobial peptides (AMPs) produced during stationary-phase growth. Furthermore, our results showed that introducing either BVM7 vegetative cells or spores into mice precolonized with V. cholerae or Enterococcus faecalis significantly reduced the burden of infection. Interestingly, we also observed that BVM7 was sensitive to a group of Lactobacillus probiotic strains and that inoculation of Lactobacilli could eliminate BVM7 and potentially restore the native gut microbiome. These findings highlight the potential of bacteria from the gut microbiome as a source for novel antimicrobial compounds and a tool for managing bacterial infections by in situ bio-delivery of multiple AMPs.IMPORTANCE The rise of antibiotic-resistant pathogens poses a challenge to public health. The gut microbiome presents a promising source of new antimicrobials and treatments. By screening murine gut commensals, we found a spore-forming Bacillus velezensis strain, BVM7, that exhibited antimicrobial activity toward a wide array of enteric and opportunistic bacterial pathogens. In addition to showing that this killing effect occurred through the action of secreted antimicrobial peptides (AMPs), we demonstrate that BVM7 vegetative cells and spores can be used to treat infections of both Gram-positive and Gram-negative pathogens in vivo. By expanding our knowledge of the antimicrobial properties of bacteria in the gut microbiome, we hope to contribute insights for developing novel drugs and therapeutic interventions.