Satellite phage TLCφ enables toxigenic conversion by CTX phage through dif site alteration

Hassan, Faizule; Kamruzzaman, Muhammad; Mekalanos, John J.; Faruque, Shah M.

doi:10.1038/nature09469

Cited by 103 publications

(104 citation statements)

References 22 publications

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“…In another example, the DNA element toxin-linked cryptic uses the morphogenesis genes of the filamentous phage fs2ϕ to form transducing phage particles. When this phage is integrated into the Vibrio cholerae chromosome by lysogeny, it restores the attachment site for integration of the cholera toxin-producing phage CTXϕ (21,22). Similarly, the ϕV7 prophage uses the structural genes of ϕV1 for its transmission in concert with transmission of ϕV1 DNA.…”

Section: Discussionmentioning

confidence: 99%

A composite bacteriophage alters colonization by an intestinal commensal bacterium

Duerkop¹,

Clements

Rollins

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

211

194

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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...

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Section: Discussionmentioning

confidence: 99%

A composite bacteriophage alters colonization by an intestinal commensal bacterium

Duerkop¹,

Clements

Rollins

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

211

194

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“…The complete genome of TLCϕ was obtained by PCR amplification using N16961 genomic DNA as a template (15). It was labeled with a cat resistance gene and was delivered to V. cholerae by conjugation.…”

Section: Resultsmentioning

confidence: 99%

“…However, IMEXs of the VGJϕ family are only very rarely found integrated in front of CTXϕ in the genome of clinical and environmental strains (4,6,7). In contrast, TLCϕ is almost invariably the first integrated element of chrI IMEX arrays (4, 6, 7), probably because its integration is a prerequisite to CTXϕ integration on this chromosome (14,15). Taken together, these results suggest that Xer recombination between attP TLC and dif1 is the most likely mechanism for the elimination of entire chrI IMEX arrays.…”

Section: Discussionmentioning

confidence: 99%

“…VGJϕ particles have a different receptor than CTXϕ, which permits transduction of the cholera toxin genes to cells that do not express the receptor of CTXϕ (11)(12)(13). Finally, integration of the toxinlinked cryptic phage (TLCϕ), a satellite phage that defines a third category of IMEXs, seems to be a prerequisite to the toxigenic conversion of many V. cholerae strains (14,15). IMEXs from this family are found integrated in the genome of many bacteria outside of the Vibrios, including human, animal, and plant pathogens, which sparked considerable interest in the understanding of how they exploit the Xer machinery at the molecular level (3,4).…”

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confidence: 99%

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XerD-mediated FtsK-independent integration of TLCϕ into the Vibrio cholerae genome

Midonet

Das

Paly

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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As in most bacteria, topological problems arising from the circularity of the two Vibrio cholerae chromosomes, chrI and chrII, are resolved by the addition of a crossover at a specific site of each chromosome, dif, by two tyrosine recombinases, XerC and XerD. The reaction is under the control of a cell division protein, FtsK, which activates the formation of a Holliday Junction (HJ) intermediate by XerD catalysis that is resolved into product by XerC catalysis. Many plasmids and phages exploit Xer recombination for dimer resolution and for integration, respectively. In all cases so far described, they rely on an alternative recombination pathway in which XerC catalyzes the formation of a HJ independently of FtsK. This is notably the case for CTXϕ, the cholera toxin phage. Here, we show that in contrast, integration of TLCϕ, a toxin-linked cryptic satellite phage that is almost always found integrated at the chrI dif site before CTXϕ, depends on the formation of a HJ by XerD catalysis, which is then resolved by XerC catalysis. The reaction nevertheless escapes the normal cellular control exerted by FtsK on XerD. In addition, we show that the same reaction promotes the excision of TLCϕ, along with any CTXϕ copy present between dif and its left attachment site, providing a plausible mechanism for how chrI CTXϕ copies can be eliminated, as occurred in the second wave of the current cholera pandemic. cholera | site-specific DNA recombination | lysogenic conversion | chromosome segregation | lateral gene transfer

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“…It is usually found integrated downstream of CTXf in the dif site of the largest V. cholerae chromosome. 12 In contrast to RstA and PII VGJf , structural analysis of the initiator protein of TLCf, Cri, revealed striking similarity with the initiator proteins of Ff coliphages. Two domains, pfam05144 and pfam05155, are conserved in these phages.…”

Section: Introductionmentioning

confidence: 99%

CTXφ: Exploring new alternatives in host factor-mediated filamentous phage replications

2016

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For a long time Ff phages from Escherichia coli provided the majority of the knowledge about the rolling circle replication mechanism of filamentous phages. Host factors involved in coliphages replication have been fully identified. Based on these studies, the function of Rep protein as the accessory helicase directly implicated in filamentous phage replication was considered a paradigm. We recently reported that the replication of some filamentous phages from Vibrio cholerae, including the cholera toxin phage CTXf, depended on the accessory helicase UvrD instead of Rep. We also identified HU protein as one of the host factors involved in CTXf and VGJf replication. The requirement of UvrD and HU for rolling circle replication was previously reported in some family of plasmids but had no precedent in filamentous phages. Here, we enrich the discussion of our results and present new preliminary data highlighting remarkable divergence in the lifestyle of filamentous phages.

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Satellite phage TLCφ enables toxigenic conversion by CTX phage through dif site alteration

Cited by 103 publications

References 22 publications

A composite bacteriophage alters colonization by an intestinal commensal bacterium

A composite bacteriophage alters colonization by an intestinal commensal bacterium

XerD-mediated FtsK-independent integration of TLCϕ into the Vibrio cholerae genome

CTXφ: Exploring new alternatives in host factor-mediated filamentous phage replications

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