Colocalisation of lanthipeptide production with genetic exchange and defence systems across prokaryote genomes

Bacteriocin production is a widespread trait among bacteria and has been shown to have a role in bacterial competition in complex communities. Lanthipeptides are a class of modified bacteriocins that can have both antibacterial and signalling activities and rely on a number of genes encoding production, modification, regulation and immunity. This study aimed to investigate whether class II lanthipeptide gene clusters co-locate with other encoded apparently unrelated functions. A total of 1,412 verified lanthipeptide biosynthetic gene clusters (BGCs) were analysed for their co-localisation with other functions over a 40 kb span. We found that genes involved in phage defence were among the most commonly located close to the bacteriocin BGCs. This phenomenon was found across species, such as Paenibacillus larvae and Corynebacterium matruchotii ATCC 33806, that have restriction modification (RM) systems. Anti-phage-defence proteins were also found in 1.2% of sampled regions and these include the anti-restriction protein ArdA. Genes related to bacterial competence were also discovered close to bacteriocin genes in genera such as Bacillus, Enterococcus and Streptococcus. This over-representation of genes encoding DNA defence systems and systems associated with the uptake of exogenous DNA near class II lanthipeptide gene clusters suggests an evolutionary rationale in which bacteriocin-mediated killing/lysis is linked to DNA uptake and horizontal gene transfer. The presence of anti-CRISPR proteins and RM-systems also suggests convergence of genetic systems that perpetuate their own survival through mutually-beneficial genomic co-localisation. This, coupled with recent evidence showing co-transcription of ribosomally-synthesised peptides and phage defence systems, suggests that the production of antimicrobial peptides forms part of a broader system where bacterial antagonism and competition is linked to horizontal gene transfer and competence as observed in streptococci.