Nisin-like biosynthetic gene clusters are widely distributed across microbiomes

Area of Science:

• Microbiology and Molecular Biology
• Antimicrobial Peptides
• Genomics and Bioinformatics

Background:

• Bacteriocins, like nisin, are potent antimicrobials with therapeutic potential.
• Nisin's impact on the gut microbiome is known, but its natural abundance, variant diversity, and antimicrobial potency remain understudied.
• Understanding nisin's prevalence is crucial for its application as a biotherapeutic agent.

Purpose of the Study:

• To investigate the prevalence and diversity of nisin biosynthetic gene clusters (nBGCs) across global microbiomes.
• To identify novel nisin variants and assess their antimicrobial activity.
• To explore the potential for horizontal gene transfer and adaptation of nBGCs.

Main Methods:

• Analysis of publicly available genomic datasets to identify nisin biosynthetic gene clusters (nBGCs).
• Bioinformatic prediction of nBGC location on mobile genetic elements.
• Heterologous expression and antimicrobial activity testing of novel nisin variants.

Main Results:

• Identified widespread and diverse nBGCs, with 30% located on mobile genetic elements, including in pathogenic bacteria.
• Evidence of horizontal gene transfer of nBGCs between bacterial genera was observed.
• Described 107 novel nisin-like peptides, with five exhibiting antimicrobial activity upon heterologous expression. Characterized nisin VP with a novel hinge region.

Conclusions:

• Nisin-like gene clusters are globally distributed and highly diverse, suggesting a significant role in microbial competition.
• The discovery of numerous novel nisin variants with antimicrobial activity underscores their biotherapeutic potential.
• Horizontal gene transfer contributes to the dissemination and adaptation of nisin production capabilities across different bacterial species.