Phage resistance mutations in a marine bacterium impact biogeochemically relevant cellular processes

Phage–bacteria interactions shape ecology and biogeochemistry across biomes. Resistance, arising from their evolutionary arms race, is well documented for receptor mutations, but other resistance mechanisms and their ecological implications remain unexplored. Here we isolated, sequenced and characterized 13 phage-resistant mutants of marine Cellulophaga baltica (Flavobacteriia). Mechanistically, mutations in surface proteins provided broad and complete extracellular resistance against multiple phages through decreased adsorption. Intracellular mutations affecting serine, glycine and threonine metabolism produced narrower resistance against a single phage, permitting viral DNA replication, and, in one mutant, were shown to be lipid mediated. Putative ecosystem impacts inferred from in vitro experiments include: (1) altered carbon utilization for all mutants, but especially by surface ones, (2) increased metabolite secretion for one modelled intracellular mutant (including experimentally verified acetate) and (3) increased ‘stickiness’ for all mutants, with surface mutants also sedimenting faster. Our findings highlight new resistance mechanisms and suggest that the phage–host arms race could result in ecosystem-level biogeochemical impacts in marine microorganisms.