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. 2014 Sep 18;10(9):e1004384.
doi: 10.1371/journal.ppat.1004384. eCollection 2014 Sep.

Molecular insights into the evolutionary pathway of Vibrio cholerae O1 atypical El Tor variants

Affiliations

Molecular insights into the evolutionary pathway of Vibrio cholerae O1 atypical El Tor variants

Eun Jin Kim et al. PLoS Pathog. .

Abstract

Pandemic V. cholerae strains in the O1 serogroup have 2 biotypes: classical and El Tor. The classical biotype strains of the sixth pandemic, which encode the classical type cholera toxin (CT), have been replaced by El Tor biotype strains of the seventh pandemic. The prototype El Tor strains that produce biotype-specific cholera toxin are being replaced by atypical El Tor variants that harbor classical cholera toxin. Atypical El Tor strains are categorized into 2 groups, Wave 2 and Wave 3 strains, based on genomic variations and the CTX phage that they harbor. Whole-genome analysis of V. cholerae strains in the seventh cholera pandemic has demonstrated gradual changes in the genome of prototype and atypical El Tor strains, indicating that atypical strains arose from the prototype strains by replacing the CTX phages. We examined the molecular mechanisms that effected the emergence of El Tor strains with classical cholera toxin-carrying phage. We isolated an intermediary V. cholerae strain that carried two different CTX phages that encode El Tor and classical cholera toxin, respectively. We show here that the intermediary strain can be converted into various Wave 2 strains and can act as the source of the novel mosaic CTX phages. These results imply that the Wave 2 and Wave 3 strains may have been generated from such intermediary strains in nature. Prototype El Tor strains can become Wave 3 strains by excision of CTX-1 and re-equipping with the new CTX phages. Our data suggest that inter-chromosomal recombination between 2 types of CTX phages is possible when a host bacterial cell is infected by multiple CTX phages. Our study also provides molecular insights into population changes in V. cholerae in the absence of significant changes to the genome but by replacement of the CTX prophage that they harbor.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Genetic map of CTX phages of Vibrio cholerae O1 El Tor Wave 3 atypical strains aligned with Wave 1 strain N16961 (genomes not shown to scale).
ctxAB of N16961 (ctxB genotype 3) is shown in blue, and ctxABs (classical ctxB, or ctxB genotype 1) of CTX-3, CTX-4, CTX-5, and CTX-6 are shown in red. ctxB of genotype 7 (Haiti strain type) of CTX-3b and CTX-6b is shown in purple. SNPs of rstA and rstB are shown as superscripts (position 927, 933, and 942 of rstA and positions 74–76, 87, 93, 105, and 189 of rstB). Del indicates 3-nucleotide (74–76 of rstB) deletion.
Figure 2
Figure 2. Generation of Wave 2 strains by excision of CTX-1 and RS1 from V212-1.
V212-1 can be converted into several variants that belong to Wave 2 strains by excision of RS1s, CTX-1, and TLC (toxin-linked cryptic) from chromosome 1. Six variants of V212-1—PM1, PM2, PM3, PM4, PM5, and PM6—were generated in this report. Although PM4 and PM5 were generated from PM3 in this report, they could be generated directly from V212-1. RS1 is shown as a rectangle divided into 2 parts: RS2 (yellow) and rstC (white). CTX is shown as a rectangle divided into 3 parts: RS2 (white for CTX-1, grey for CTX-2), core, and ctxB (El Tor type ctxB is shown in blue and classical type ctxB is shown in red).
Figure 3
Figure 3. The generation of new mosaic CTX phages from V212-1 by inter-strand recombination between CTX phages and intra-strand recombination between CTX-1 and RS1 on chromosome 1.
A double crossover recombination event between 2 prophages on each chromosome of V212-1 (indicated by arrows) results in the generation of the CTX-1* prophage which contains ctxB cla on chromosome 1. Intra-stand recombination between CTX-1* and RS1 generates a mosaic CTX prophage. Depending on the recombination position (shown as R1, R2, and R3), CTX-3, -5, and -6 can be generated (CTX-4 can also be generated, but not shown in this figure). The infectious CTX-3, -5, or -6 virions can be transduced to a new host to give rise to Wave 3 strains.
Figure 4
Figure 4. A model of the generation of Wave 2 and Wave 3 strains.
Prototype El Tor strains transform into an intermediary strain by CTX-2 phage infection. It is unknown how the CTX-2 phage was generated, but we hypothesize that CTX-2 is generated in a strain containing CTX-1 and CTXcla. The intermediary stain is converted into Wave 2 strains by stepwise removal of CTX-1 and RS1. Mosaic CTX phages, such as CTX-3, CTX-4, are generated from the intermediary strain, and transduced into a new host bacterial strain that harbors only RS1 on chromosome 1, resulting in Wave 3 strains. ctxB type 1 of some Wave 3 strains is further converted into ctxB type 7 by a point mutation.

References

    1. Kaper JB, Morris JG Jr, Levine MM (1995) Cholera. Clin Microbiol Rev 8: 48–86. - PMC - PubMed
    1. Sack DA, Sack RB, Nair GB, Siddique AK (2004) Cholera. Lancet 363: 223–233. - PubMed
    1. Choi SY, Lee JH, Kim EJ, Lee HR, Jeon YS, et al. (2010) Classical RS1 and environmental RS1 elements in Vibrio cholerae O1 El Tor strains harbouring a tandem repeat of CTX prophage: revisiting Mozambique in 2005. J Med Microbiol 59: 302–308. - PubMed
    1. Boyd EF, Heilpern AJ, Waldor MK (2000) Molecular analyses of a putative CTXΦ precursor and evidence for independent acquisition of distinct CTXΦs by toxigenic Vibrio cholerae . J Bacteriol 182: 5530–5538. - PMC - PubMed
    1. Nair GB, Qadri F, Holmgren J, Svennerholm AM, Safa A, et al. (2006) Cholera due to altered El Tor strains of Vibrio cholerae O1 in Bangladesh. J Clin Microbiol 44: 4211–4213. - PMC - PubMed

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