Human-gut phages harbor sporulation genes

Spore-forming bacteria are prevalent in mammalian guts and have implications for host health and nutrition. The production of dormant spores is thought to play an important role in the colonization, persistence, and transmission of these bacteria. Spore formation also modifies interactions among microorganisms such as infection by phages. Recent studies suggest that phages may counter dormancy-mediated defense through the expression of phage-encoded sporulation genes during infection, which can alter the transitions between active and inactive states. By mining genomes and gut-derived metagenomes, we identified sporulation genes that are preferentially encoded by phages that infect spore-forming bacteria. These included genes involved in chromosome partitioning, DNA damage repair, and cell wall-associated functions. In addition, phages contained homologs of sporulation-specific transcription factors, notably spo0A, the master regulator of sporulation, which could allow phages to control the complex genetic network responsible for spore development. Our findings suggest that phages could influence the formation of bacterial spores with implications for the health of the human gut microbiome, as well as bacterial communities in other environments. SIGNIFICANCEPhages acquire bacterial genes and use them to alter host metabolism in ways that enhance their fitness. To date, most auxiliary genes replace or modulate enzymes that are used by the host for nutrition or energy production. However, phage fitness is affected by all aspects of host physiology, including decisions that reduce metabolic activity of the cell. Here we focus on endosporulation, a complex and ancient form of dormancy found among the Bacillota that involves hundreds of genes. By coupling homology searches with host classification, we identify 31 phage-encoded homologs of sporulation genes that are mostly limited to phages infecting spore-forming bacteria. Nearly one-third the homologs recovered were regulatory genes suggesting that phages may manipulate host genetic networks by tapping into their control elements. Our findings also suggest a mechanism by which phages can overcome the defensive strategy of dormancy, which may be involved in coevolutionary dynamics of spore-forming bacteria.