A composite bacteriophage alters colonization by an intestinal commensal bacterium

Abstract

The mammalian intestine is home to a dense community of bacteria and its associated bacteriophage (phage). Virtually nothing is known about how phages impact the establishment and maintenance of resident bacterial communities in the intestine. Here, we examine the phages harbored by Enterococcus faecalis, a commensal of the human intestine. We show that E. faecalis strain V583 produces a composite phage (ϕV1/7) derived from two distinct chromosomally encoded prophage elements. One prophage, prophage 1 (ϕV1), encodes the structural genes necessary for phage particle production. Another prophage, prophage 7 (ϕV7), is required for phage infection of susceptible host bacteria. Production of ϕV1/7 is controlled, in part, by nutrient availability, because ϕV1/7 particle numbers are elevated by free amino acids in culture and during growth in the mouse intestine. ϕV1/7 confers an advantage to E. faecalis V583 during competition with other E. faecalis strains in vitro and in vivo. Thus, we propose that E. faecalis V583 uses phage particles to establish and maintain dominance of its intestinal niche in the presence of closely related competing strains. Our findings indicate that bacteriophages can impact the dynamics of bacterial colonization in the mammalian intestinal ecosystem.T he human gastrointestinal tract is colonized with a highly diverse population of bacteria (1). Many of these bacteria produce bacteriophage (phage), further increasing the complexity of this ecosystem. Recent studies of human intestinal viromes have shown that these viromes are dominated by lysogenic prophages that are integrated into the chromosomes of their bacterial hosts (2). In numerous other ecological systems, phages profoundly influence ecological networks by serving as reservoirs of genetic diversity (3, 4) and acting as predators of susceptible bacterial strains (5). However, little is known about how resident phages may influence the assembly and maintenance of bacterial communities in the mammalian intestine.Enterococcus faecalis is an abundant member of the human intestinal microflora, and by adulthood, it can constitute as much as 0.5-0.9% of the total bacterial content of the intestinal tract (Table S1) (6). A Gram-positive facultative anaerobe, E. faecalis is a leading cause of antibiotic-resistant nosocomial bacteremia and endocarditis (7). Genomic sequencing has revealed a high degree of variation among E. faecalis genomes (8). Some of this variation can be attributed to an array of integrated prophage elements that encode components required for the production of phage particles.The first E. faecalis genome to be sequenced was strain V583, a clinical blood isolate that is vancomycin-resistant (9). The V583 chromosome harbors seven putative prophages designated prophages 1-7 (Fig. 1). At least two of these prophage elements seem to encode cryptic or satellite phage genomes (10) that, by themselves, do not produce functional phage particles but may encode accessory components that aid in the lytic cycle of other integrated pro...

Phage and bacteria support mutual diversity in a narrowing staircase of coexistence

“…These situations reflect a phage strain that weakly adheres to the slow grower B 2 , but causes relatively more damage to B 1 . From this result we predict a possible virulentphage variant of the experimentally observed 'suicide bombing' recently found for temperate prophages (Duerkop et al, 2012). In other words, although bacterial strains are under evolutionary pressure to increase their net growth rate Bk À a, a fast grower occasionally can be attacked by a combination of a bacterial strain with slow growth rate and a phage strain that preferentially eliminates the fast grower.…”

Gnotobiotic mouse model of phage–bacterial host dynamics in the human gut

“…Using a more complex defined microbiota, we also observe a diverse range of viral dynamics: (i) exogenous viruses rising in abundance soon after their introduction (with a corresponding decrease in abundance of their putative bacterial hosts) followed by depletion of these viruses from the community without any obvious trace of genetic resistance or adaptation; (ii) exogenous viruses that survive at undetectable levels for almost a week before increasing their abundances, and in one case, displaying genetic variability over time; and (iii) basal levels of induction of 10 prophages with only one prophage achieving a level that produced detectable alteration in the abundance of its bacterial host. Duerkop et al also showed that prophage induction differed in vitro and in vivo, and how under the appropriate conditions induction could provide a fitness benefit to the bacterial host (27), further highlighting the importance of a temperate lifestyle in the gut, and why prophages are so widely distributed in gut bacterial genomes without necessarily being induced at significant levels. Our findings are also consistent with the previous finding that T7 phages are capable of surviving at undetectable levels for 1 wk in germ-free animals before they rise in abundance after gavage of a bacterial host (26); this capacity to maintain infectivity has potential implications for preventive phage therapy.…”

Human oral viruses are personal, persistent and gender-consistent

“…Many of the viruses in these communities are bacteriophage (Breitbart et al, 2003;Minot et al, 2011;Willner et al, 2011;Pride et al, 2012a;Minot et al, 2013), likely secondary to the abundance of bacterial cells compared with eukaryote cells in these communities. Viruses likely have a key role in microbial population structures by altering the composition of bacterial communities (Duerkop et al, 2012). The interaction of bacteria and viruses is thought to maintain broad bacterial diversity in the local environment via various ecological models, such as constant-diversity dynamics, periodic selection dynamics and kill-the-winner dynamics (Parada et al, 2008;Rodriguez-Valera et al, 2009;Sandaa et al, 2009;Rodriguez-Brito et al, 2010;Allen et al, 2011).…”