RS1 Satellite Phage Promotes Diversity of Toxigenic Vibrio cholerae by Driving CTX Prophage Loss and Elimination of Lysogenic Immunity

Kamruzzaman, Muhammad; Robins, William; Bari, S. M. Nayeemul; Nahar, Shamsun; Mekalanos, John J.; Faruque, Shah M.

doi:10.1128/iai.01699-14

Cited by 17 publications

(15 citation statements)

References 39 publications

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“…The deletion in the 2012Env-9/390 genomes encompasses CTXϕ and satellite phages TLCϕ and RS1ϕ, which are present in canonical toxigenic O1 strains18. The absence of CTXϕ core genes ( cep , orfU , ace , and zot ) and RS1 element ( rstR , rstA , rstB , and rstC ) were confirmed through BLAST searches of 2012Env-9/390.…”

Section: Resultsmentioning

confidence: 89%

Non-toxigenic environmental Vibrio cholerae O1 strain from Haiti provides evidence of pre-pandemic cholera in Hispaniola

Azarian

Ali

Johnson

et al. 2016

Sci Rep

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Vibrio cholerae is ubiquitous in aquatic environments, with environmental toxigenic V. cholerae O1 strains serving as a source for recurrent cholera epidemics and pandemic disease. However, a number of questions remain about long-term survival and evolution of V. cholerae strains within these aquatic environmental reservoirs. Through monitoring of the Haitian aquatic environment following the 2010 cholera epidemic, we isolated two novel non-toxigenic (ctxA/B-negative) Vibrio cholerae O1. These two isolates underwent whole-genome sequencing and were investigated through comparative genomics and Bayesian coalescent analysis. These isolates cluster in the evolutionary tree with strains responsible for clinical cholera, possessing genomic components of 6th and 7th pandemic lineages, and diverge from “modern” cholera strains around 1548 C.E. [95% HPD: 1532–1555]. Vibrio Pathogenicity Island (VPI)-1 was present; however, SXT/R391-family ICE and VPI-2 were absent. Rugose phenotype conversion and vibriophage resistance evidenced adaption for persistence in aquatic environments. The identification of V. cholerae O1 strains in the Haitian environment, which predate the first reported cholera pandemic in 1817, broadens our understanding of the history of pandemics. It also raises the possibility that these and similar environmental strains could acquire virulence genes from the 2010 Haitian epidemic clone, including the cholera toxin producing CTXϕ.

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Section: Resultsmentioning

confidence: 89%

Non-toxigenic environmental Vibrio cholerae O1 strain from Haiti provides evidence of pre-pandemic cholera in Hispaniola

Azarian

Ali

Johnson

et al. 2016

Sci Rep

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“…All of the V. mimicus strains in this study were observed to produce replicative forms of both CTXФ ET and pre-CTXФ Env when induced by mitomycinC in the culture filtrates, which was detected by PCRs after DNAse and RNAse treatment (data not shown). On the other hand, like the El Tor strains of V. cholerae , the environmental V. mimicus strains also harbored rstC , i.e., the RS1 element, which has been recently observed to promote diversity by the loss of CTX prophage and lysogenic immunity to make room for new CTX prophage to be integrated (29). Presence of rstC has been shown to increase rstA transcription and CTXФ production (17), which may influence ctxAB transcription and diversification.…”

Section: Discussionmentioning

confidence: 99%

Novel cholera toxin variant and ToxT regulon in environmentalVibrio mimicusstrains: potential resources for the evolution ofVibrio choleraehybrid strains

Neogi¹,

Chowdhury²,

Awasthi³

et al. 2018

Preprint

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23Atypical El Tor strains of Vibrio cholerae O1 harboring variant ctxB genes of cholera toxin 24 (CT) are gradually becoming a major cause of recent cholera epidemics. Vibrio mimicus 25 occasionally contains virulence factors associated with cholera, e.g., CT, encoded by ctxAB 26 on CTXФ genome; and TCP, the CTXФ-specific receptor. This study carried out extensive 27 molecular characterization of CTXФ and ToxT regulon in ctx +ve strains of V. mimicus 28 isolated from the Bengal coast. Southern hybridization, PCR, and DNA sequencing of 29 virulence related-genes revealed the presence of an El Tor type CTX prophage (CTX ET ) 30 carrying a novel ctxAB, tandem copies of environmental type pre-CTX prophage (pre-31 CTX Env ), and RS1 elements, which were organized in an array of RS1-CTX ET -RS1-pre-32 CTX Env -pre-CTX Env . Additionally, a novel variant of tcpA and toxT respectively, showing 33 clonal lineage to a phylogenetic clade of V. cholerae non-O1/O139, was identified. The V. 34 mimicus strains lacked the RTX and TLC elements, and Vibrio seventh pandemic islands of 35 the El Tor strains, but contained five heptamer (TTTTGAT) repeats in ctxAB promoter region 36 like some classical strains of V. cholerae O1. PFGE analysis showed all the ctx +ve V. mimicus 37 strains were clonally related. However, their in vitro CT production and in vivo toxigenecity 38 were variable, which could be explained by differential transcription of virulence genes along 39 with ToxR regulon. Taken together, our findings strongly suggest that environmental V. 40 mimicus strains act as potential reservoir of atypical virulence factors, including variant CT 41 and ToxT regulon, and may contribute to the evolution of V. cholerae hybrid strains. 42 (248/250 words) 43 IMPORTANCE 44 Natural diversification of CTXФ and ctxAB genes certainly influences disease severity and 45 shifting patterns in major etiological agents of cholera, e.g., the overwhelming emergence of 46 hybrid El Tor variants, replacing the prototype El Tor strains of V. cholerae. This study 47 showing the occurrence of CTX ET comprising a novel variant of ctxAB in V. mimicus points 48 out a previously unnoticed evolutionary event, independent to that of the El Tor strains of V. 49 cholerae. Identification and cluster analysis of the newly-discovered alleles of tcpA and toxT 50 indicates their horizontal transfer from an uncommon clone of V. cholerae. The genomic 51 content of ToxT regulon, and tandemly arranged multiple pre-CTXФ Env and a CTXФ ET in V. 52 mimicus probably act as salient raw materials inducing natural recombination among the 53 hallmark virulence genes of hybrid V. cholerae strains. This study will facilitate deeper 54 understanding of the evolution of new variant CT and ToxT regulon, influencing cholera 55 epidemiology. 56 (150/150 words) 57 58 Vibrio mimicus is genetically and ecologically very similar to Vibrio cholerae, the 59 cholera bacterium and share similar environmental niche in freshwater and estuarine 60 ecosystems, particularly ...

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“…To our knowledge, the only other tyrosine recombinase for which efficient recombination between half-sites has been observed is Flp, the flippase of the 2-μm plasmid of Saccharomyces cerevisiae. Flp normally works as a homotetramer; however, in case of recombination between half-sites and full sites, the synapses imply three recombinases (27). In the case of Flp, trimer recombination is possibly related to the fact that active sites are assembled in trans (28).…”

Section: Discussionmentioning

confidence: 99%

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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RS1 Satellite Phage Promotes Diversity of Toxigenic Vibrio cholerae by Driving CTX Prophage Loss and Elimination of Lysogenic Immunity

Cited by 17 publications

References 39 publications

Non-toxigenic environmental Vibrio cholerae O1 strain from Haiti provides evidence of pre-pandemic cholera in Hispaniola

Non-toxigenic environmental Vibrio cholerae O1 strain from Haiti provides evidence of pre-pandemic cholera in Hispaniola

Novel cholera toxin variant and ToxT regulon in environmentalVibrio mimicusstrains: potential resources for the evolution ofVibrio choleraehybrid strains

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

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