Abstract
The gut microbiota harbors a diverse phage population that is largely derived from lysogens, which are bacteria that contain dormant phages in their genome. While the diversity of phages in gut ecosystems is getting increasingly well characterized, knowledge is limited on how phages contribute to the evolution and ecology of their host bacteria. Here, we show that biologically active prophages are widely distributed in phylogenetically diverse strains of the gut symbiont Lactobacillus reuteri Nearly all human- and rodent-derived strains, but less than half of the tested strains of porcine origin, contain active prophages, suggesting different roles of phages in the evolution of host-specific lineages. To gain insight into the ecological role of L. reuteri phages, we developed L. reuteri strain 6475 as a model to study its phages. After administration to mice, L. reuteri 6475 produces active phages throughout the intestinal tract, with the highest number detected in the distal colon. Inactivation of recA abolished in vivo phage production, which suggests that activation of the SOS response drives phage production in the gut. In conventional mice, phage production reduces bacterial fitness as fewer wild-type bacteria survive gut transit compared to the mutant lacking prophages. However, in gnotobiotic mice, phage production provides L. reuteri with a competitive advantage over a sensitive host. Collectively, we uncovered that the presence of prophages, although associated with a fitness trade-off, can be advantageous for a gut symbiont by killing a competitor strain in its intestinal niche.IMPORTANCE Bacteriophages derived from lysogens are abundant in gut microbiomes. Currently, mechanistic knowledge is lacking on the ecological ramifications of prophage carriage yet is essential to explain the abundance of lysogens in the gut. An extensive screen of the bacterial gut symbiont Lactobacillus reuteri revealed that biologically active prophages are widely distributed in this species. L. reuteri 6475 produces phages throughout the mouse intestinal tract, but phage production is associated with reduced fitness of the lysogen. However, phage production provides a competitive advantage in direct competition with a nonlysogenic strain of L. reuteri that is sensitive to these phages. This combination of increased competition with a fitness trade-off provides a potential explanation for the domination of lysogens in gut ecosystem and how lysogens can coexist with sensitive hosts.
Highlights
IMPORTANCE Bacteriophages derived from lysogens are abundant in gut microbiomes
We show that active prophages are distributed among a broad range of phylogenetically diverse strains within the species Lactobacillus reuteri, which suggests that the gut environment selects for a temperate lifestyle
We mapped the prophage distribution in 28 L. reuteri strains of vertebrate origin and identified 17 genomes that are predicted to encode intact prophages, while most genomes contained incomplete prophages or phage remnants (Table 1). To expand on this observation, we assessed the distribution of biologically active prophages in this species by screening an extensive library of L. reuteri strains with mitomycin C (MMC), which activates the bacterial SOS response and cues the prophages to excise and lyse the bacterial cell
Summary
IMPORTANCE Bacteriophages derived from lysogens are abundant in gut microbiomes. Currently, mechanistic knowledge is lacking on the ecological ramifications of prophage carriage yet is essential to explain the abundance of lysogens in the gut. Phage production provides a competitive advantage in direct competition with a nonlysogenic strain of L. reuteri that is sensitive to these phages This combination of increased competition with a fitness trade-off provides a potential explanation for the domination of lysogens in gut ecosystem and how lysogens can coexist with sensitive hosts. Much less is known about the ecology and evolution of lysogenic phages, especially in gut ecosystems In human feces, it is estimated there are ϳ1011 bacterial cells gϪ1 and up to 1010 virus-like particles gϪ1 [7, 8], which include temperate phages [3]. Experimental evidence is lacking to substantiate claims linking beneficial or detrimental effects to the presence of prophages This lack of knowledge stems from the absence of mechanistic studies that investigate to what extent prophages impact gut bacterial ecology and fitness in realistic model organisms in relevant experimental settings. These findings were not species or strain specific as exposure to short-chain fatty acids promoted phage production in Lactococcus lactis and in L. reuteri ATCC 55730 [15], a strain that is genetically distinct from L. reuteri 6475 [36]
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