Genomic Analysis of Bacteria of the Genus Methylococcus for Defence Systems against Bacteriophages

Methylococcus species utilize methane as the sole carbon and energy source, converting it into biomass and other metabolic end products. Owing to this metabolic capacity, they hold particular promise in industrial C1 biotechnology, especially for the production of protein-rich feed. However, the industrial cultivation of Methylococcus-based consortia on methane is inherently non-sterile, exposing the process to potential biological risks that may compromise the stability, duration and productivity of cultivation. One of the most critical threats is bacteriophage infection, whose triggers for rapid phage-mediated lysis and resulting economic losses remain incompletely understood. Here, we performed a comparative genomic analysis of 9 Methylococcus strains to systematically identify and characterize their antiphage defence systems. We detected between 8 and 15 systems per strain, with restriction–modification (RM), SoFic, CRISPR-Cas, and BREX being the most prevalent. Together, these mechanisms form a conserved multilayered defence core acting at different infection stages. Additional strain-specific systems, including direct phage-sensing and DNA-cleaving, replication-inhibiting, and abortive infection modules, indicate horizontal gene transfer and ecological adaptation. Notably, strains KN2, Mc7, and McNor encode the most diverse and potentially synergistic defence combinations, highlighting their strong protective potential and relevance for stable methane bioconversion under industrial conditions.