A genomic island in Vibrio cholerae with VPI-1 site-specific recombination characteristics contains CRISPR-Cas and type VI secretion modules

Labbate, Maurizio; Orata, Fabini D.; Petty, Nicola K.; Jayatilleke, Nathasha D.; King, William L.; Kirchberger, Paul C.; Allen, C.; Mann, Gülay; Mutreja, Ankur; Thomson, Nicholas R.; Boucher, Yan; Charles, Ian G.

doi:10.1038/srep36891

Cited by 43 publications

(62 citation statements)

References 47 publications

(62 reference statements)

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“…this uncharacterized allele VgrG-4. Moreover, we found that Hcp and VgrG-4 alleles from GIVch-T6SS Santiago-089 are also harboured by the GIVchS12 [27]. Thus, the identification of T3SS genes and the VgrG-4 allele in non-O1/non-O139 strains of several lineages suggests these GIs are widely distributed (Fig.…”

Section: Resultsmentioning

confidence: 67%

Genomic characterization of the non-O1/non-O139 Vibrio cholerae strain that caused a gastroenteritis outbreak in Santiago, Chile, 2018

Arteaga

Velasco

Rodriguez

et al. 2019

Preprint

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43Vibrio cholerae is a human pathogen which is transmitted by the consumption of contaminated 44 food or water. V. cholera strains belonging to the serogroups O1 and O139 can cause cholera 45 outbreaks and epidemics, a severe life-threatening diarrheal disease. In contrast, serogroups 46 other than O1 and O139, denominated as non-O1/non-O139, have been mainly associated with 47 sporadic cases of moderate or mild diarrhea, bacteremia and wound infections. Here we 48 investigated the virulence determinants and phylogenetic origin of a non-O1/non-O139 Vibrio 49 cholerae strain that caused a gastroenteritis outbreak in Santiago, Chile, 2018. We found that this 50 outbreak strain lacks the classical virulence genes harbored by O1 and O139 strains, including 51 the cholera toxin (CT) and the toxin-coregulated pilus (TCP). However, this strain carries genomic 52 islands (GIs) encoding Type III and Type VI secretion systems (T3SS/T6SS) and antibiotic 53 resistance genes. Moreover, we found these GIs are wide distributed among several lineages of 54 non-O1/non-O139 strains. Our results suggest that the acquisition of these GIs may enhance the 55 virulence of non-O1/non-O139 strains that lack the CT and TCP-encoding genes. Our results 56 highlight the pathogenic potential of these V. cholerae strains.

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Section: Resultsmentioning

confidence: 67%

Genomic characterization of the non-O1/non-O139 Vibrio cholerae strain that caused a gastroenteritis outbreak in Santiago, Chile, 2018

Arteaga

Velasco

Rodriguez

et al. 2019

Preprint

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“…These data indicated that VPI-6 can excise from the chromosome as a complete unit. A similar CRISPR-Cas island region in a V. cholerae strain isolated in Australia was also shown to excise from the genome, presumably using a similar mechanism (49).…”

Section: Figmentioning

confidence: 87%

CRISPR-Cas and Contact-Dependent Secretion Systems Present on Excisable Pathogenicity Islands with Conserved Recombination Modules

et al. 2017

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Pathogenicity islands (PAIs) are mobile integrated genetic elements that contain a diverse range of virulence factors. PAIs integrate into the host chromosome at a tRNA locus that contains their specific bacterial attachment site, attB, via integrase-mediated site-specific recombination generating attL and attR sites. We identified conserved recombination modules (integrases and att sites) previously described in choleragenic Vibrio cholerae PAIs but with novel cargo genes. Clustered regularly interspaced short palindromic repeat (CRISPR)-associated proteins (Cas proteins) and a type VI secretion system (T6SS) gene cluster were identified at the Vibrio pathogenicity island 1 (VPI-1) insertion site in 19 V. cholerae strains and contained the same recombination module. Two divergent type I-F CRISPR-Cas systems were identified, which differed in Cas protein homology and content. The CRISPR repeat sequence was identical among all V. cholerae strains, but the CRISPR spacer sequences and the number of spacers varied. In silico analysis suggests that the CRISPR-Cas systems were active against phages and plasmids. A type III secretion system (T3SS) was present in 12 V. cholerae strains on a 68-kb island inserted at the same tRNA-serine insertion site as VPI-2 and contained the same recombination module. Bioinformatics analysis showed that two divergent T3SSs exist among the strains examined. Both the CRISPR and T3SS islands excised site specifically from the bacterial chromosome as complete units, and the cognate integrases were essential for this excision. These data demonstrated that identical recombination modules that catalyze integration and excision from the chromosome can acquire diverse cargo genes, signifying a novel method of acquisition for both CRISPR-Cas systems and T3SSs. IMPORTANCE This work demonstrated the presence of CRISPR-Cas systems and T3SSs on PAIs. Our work showed that similar recombination modules can associate with different cargo genes and catalyze their incorporation into bacterial chromosomes, which could convert a strain into a pathogen with very different disease pathologies. Each island had the ability to excise from the chromosome as distinct, complete units for possible transfer. Evolutionary analysis of these regions indicates that they were acquired by horizontal transfer and that PAIs are the units of transfer. Similar to the case for phage evolution, PAIs have a modular structure where different functional regions are acquired by identical recombination modules.KEYWORDS CRISPR-Cas, type III secretion, Vibrio cholerae, pathogenicity islands V ibrio cholerae is the causative agent of the severe diarrheal disease cholera. The factors necessary for manifestation of this disease were acquired by horizontal gene transfer. The cholera toxin (CT), a potent enterotoxin whose effects are respon-

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“…Here we describe a site-specific recombination mechanism of T6SS effector acquisition for the Aux3 locus. The acquisition of genomic islands by this mechanism is not uncommon in V. cholerae (29)(30)(31)(32). For instance, the GIVchS12 element encodes its own integrase, excises from the chromosome to form a circular element, and carries a cluster of T6SS genes including an hcp gene and an E/I pair (32).…”

Section: Discussionmentioning

confidence: 99%

“…Several other virulence factors in V. cholerae such as CT, TCP, and the SXT element are either phage-encoded or acquired by phage-like site-specific recombination (28)(29)(30)(31)(32). In each case, integrases and transposases catalyze recombination.…”

Section: Main Text Introductionmentioning

confidence: 99%

Vibrio choleraeType VI Secretion System Auxiliary Cluster 3 is a Pandemic-associated Mobile Genetic Element

Santoriello

Michel

Unterweger

et al. 2019

Preprint

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All sequenced Vibrio cholerae isolates encode a contact-dependent type VI secretion system (T6SS) in three loci that terminate in a toxic effector and cognate immunity protein (E/I) pair, allowing for competitor killing and clonal expansion in aquatic environments and the host gut.Recent studies have demonstrated variability in the toxic effectors produced by different V. cholerae strains and the propensity for effector genes to undergo horizontal gene transfer. Here we demonstrate that a fourth cluster, auxiliary cluster 3 (Aux3), encoding the E/I pair tseH/tsiH, is located directly downstream from two putative recombinases and is flanked by repeat elements resembling att sites. Genomic analysis of 749 V. cholerae isolates, including both pandemic and environmental strains, revealed that Aux3 exists in two states: a ~40 kb prophage-like element in nine environmental isolates and a ~6 kb element in pandemic isolates. These findings indicate that Aux3 in pandemic V. cholerae is evolutionarily related to an environmental prophage-like element.In both states, Aux3 excises from the chromosome via site-specific recombination to form a circular product, likely priming the module for horizontal transfer. Finally, we show that Aux3 can integrate into the Aux3-naïve chromosome in an integrase-dependent, site-specific manner. This highlights the potential of Aux3 to undergo horizontal transfer by a phage-like mechanism, which based on pandemic coincidence may confer currently unknown fitness advantages to the recipient V. cholerae cell. Significance StatementV. cholerae is a human pathogen that causes pandemics affecting 2.8 million people annually (1).The O1 El Tor lineage is responsible for the current pandemic. A subset of non-O1 strains cause cholera-like disease by producing the major virulence factors cholera toxin and toxin co-regulated pilus but fail to cause pandemics. The full set of V. cholerae pandemic factors is unknown. Here we describe the type VI secretion system (T6SS) Aux3 element as a largely pandemic-specific factor that is evolutionarily related to an environmental prophage-like element circulating in nonpathogenic strains. These findings shed light on V. cholerae T6SS evolution and indicate the Aux3 element as a pandemic-enriched mobile genetic element.

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A genomic island in Vibrio cholerae with VPI-1 site-specific recombination characteristics contains CRISPR-Cas and type VI secretion modules

Cited by 43 publications

References 47 publications

Genomic characterization of the non-O1/non-O139 Vibrio cholerae strain that caused a gastroenteritis outbreak in Santiago, Chile, 2018

Genomic characterization of the non-O1/non-O139 Vibrio cholerae strain that caused a gastroenteritis outbreak in Santiago, Chile, 2018

CRISPR-Cas and Contact-Dependent Secretion Systems Present on Excisable Pathogenicity Islands with Conserved Recombination Modules

Vibrio choleraeType VI Secretion System Auxiliary Cluster 3 is a Pandemic-associated Mobile Genetic Element

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