Acquisition and Evolution of SXT-R391 Integrative Conjugative Elements in the Seventh-Pandemic Vibrio cholerae Lineage

Spagnoletti, Matteo; Ceccarelli, Daniela; Rieux, Adrien; Fondi, Marco; Taviani, Elisa; Fani, Renato; Colombo, Mauro; Colwell, Rita R.; Balloux, François

doi:10.1128/mbio.01356-14

Cited by 82 publications

(76 citation statements)

References 54 publications

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“…SXT/R391 ICEs are major vectors of multidrug resistance dissemination across a plethora of bacterial genera encountered in clinical and environmental settings (7)(8)(9). Their highly conserved regulatory region governs the transition between the ICE quiescent and conjugative states (24,29,30).…”

Section: Discussionmentioning

confidence: 99%

“…SXT integrates itself into the chromosome of V. cholerae in a site-specific manner at the 5= end of prfC, a gene coding for the peptide release factor RF3 (6). Since the discovery of SXT, SXT or related ICEs have been found to be prevalent in the seventh pandemic isolates of V. cholerae and sporadically present in other Vibrio species (7)(8)(9) and other Gammaproteobacteria of clinical origin or isolated from the aquatic environment, such as Photobacterium (10), Proteus (11), Alteromonas (12), Marinomonas (13), and Shewanella (9,14) species. SXT is closely related to R391, an ICE conferring resistance to kanamycin and mercury, originally detected in a 1967 South African isolate of Providencia rettgeri (15,16).…”

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confidence: 99%

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A λ Cro-Like Repressor Is Essential for the Induction of Conjugative Transfer of SXT/R391 Elements in Response to DNA Damage

Poulin-Laprade

Burrus

2015

J Bacteriol

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Integrative and conjugative elements (ICEs) of the SXT/R391 family are the main contributors to acquired multidrug resistance in the seventh pandemic lineage of Vibrio cholerae, the etiological agent of the diarrheal disease cholera. Conjugative transfer of SXT/R391 ICEs is triggered by antibiotics and agents promoting DNA damage through RecA-dependent autoproteolysis of SetR, an ICE-encoded CI-like repressor. Here, we describe the role of CroS, a distant Cro homolog, as a key component contributing to the regulation of expression of the activator SetCD that orchestrates the expression of the conjugative transfer genes. We show that deletion of croS abolishes the SOS response-dependent induction of SXT despite the presence of a functional setR gene. Using quantitative reverse transcription-PCR and lacZ reporter assays, we also show that CroS represses setR and setCD expression by binding to operator sites shared with SetR. Furthermore, we provide evidence of an additional operator site bound by SetR and CroS. Finally, we show that SetCD expression generates a positive feedback loop due to SXT excision and replication in a fraction of the cell population. Together, these results refine our understanding of the genetic regulation governing the propagation of major vectors of multidrug resistance. IMPORTANCEHealthcare systems worldwide are challenged by an alarming drug resistance crisis caused by the massive and rapid propagation of antibiotic resistance genes and the associated emergence of multidrug-resistant pathogenic bacteria. SXT/R391 ICEs contribute to this phenomenon not only in clinical and environmental vibrios but also in several members of the family Enterobacteriaceae. We have identified and characterized here the regulator CroS as a key factor in the stimulation of conjugative transfer of these ICEs in response to DNA-damaging agents. We have also untangled conflicting evidence regarding autoactivation of transfer by the master activator of SXT/R391 ICEs, SetCD. Discovery of CroS provides a clearer and more complete understanding of the regulatory network that governs the dissemination of SXT/R391 ICEs in bacterial populations. Cholera is a severe infectious disease caused by the ingestion of food or water contaminated by Vibrio cholerae. This disease remains widespread in regions with limited access to clean water and where poor sanitation allows easy dissemination of the bacterium in drinking water sources. Cholera is characterized by a profuse watery diarrhea that rapidly induces massive fluid loss, causing severe dehydration of the patient, which may lead to death within 24 h of symptom onset. Although epidemic cholera is usually caused by V. cholerae O1, the unusual serogroup O139 emerged in the early 1990s as the cause of a cholera outbreak in India (1). O139 clinical isolates were found to be resistant to sulfamethoxazole and trimethoprim, two antibiotics commonly used for the treatment of severe cases of cholera (2). This resistance was found to be transmissible and linked to an integ...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

A λ Cro-Like Repressor Is Essential for the Induction of Conjugative Transfer of SXT/R391 Elements in Response to DNA Damage

Poulin-Laprade

Burrus

2015

J Bacteriol

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“…These elements can range from ∼80 to 110 Kb in size and contain all of the genes required for conjugative transfer into naive hosts (10,11); they integrate in a site-specific manner into the 5′ end of the highly conserved prfC (peptide-chain-release factor C) gene (10)(11)(12). The first natural transfer of an ICE into V. cholerae likely occurred between 1980 and 1985 (10,13) and, by the 1990s, virtually all clinical isolates of V. cholerae contained an ICE (13). These elements confer resistance to multiple antibiotics, and it is likely that widespread use of antibiotics has rapidly selected for strains containing ICEs.…”

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confidence: 99%

“…These ICEs share a core set of genes, but have varied gene content at distinct sites. The most common ICE in V. cholerae is VchInd5, which is present in ∼77% of currently sequenced clinical isolates (10,11). It is hypothesized that the current (seventh) pandemic of cholera originated in the Bay of Bengal, and strains have spread globally from this region in three overlapping waves of transmission (13,14).…”

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confidence: 99%

A globally distributed mobile genetic element inhibits natural transformation of Vibrio cholerae

Dalia

Seed

Calderwood

et al. 2015

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

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Natural transformation is one mechanism of horizontal gene transfer (HGT) in Vibrio cholerae, the causative agent of cholera. Recently, it was found that V. cholerae isolates from the Haiti outbreak were poorly transformed by this mechanism. Here, we show that an integrating conjugative element (ICE)-encoded DNase, which we name IdeA, is necessary and sufficient for inhibiting natural transformation of Haiti outbreak strains. We demonstrate that IdeA inhibits this mechanism of HGT in cis via DNA endonuclease activity that is localized to the periplasm. Furthermore, we show that natural transformation between cholera strains in a relevant environmental context is inhibited by IdeA. The ICE encoding IdeA is globally distributed. Therefore, we analyzed the prevalence and role for this ICE in limiting natural transformation of isolates from Bangladesh collected between 2001 and 2011. We found that IdeA+ ICEs were nearly ubiquitous in isolates from 2001 to 2005; however, their prevalence decreased to ∼40% from 2006 to 2011. Thus, IdeA+ ICEs may have limited the role of natural transformation in V. cholerae. However, the rise in prevalence of strains lacking IdeA may now increase the role of this conserved mechanism of HGT in the evolution of this pathogen.

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“…It has been estimated that conjugative systems of ICEs are more abundant among bacteria than those of plasmids (7), yet we know far less about ICE behavior because they are difficult to follow and isolate. ICEs have attracted interest because they can transmit antibiotic resistance genes (8) and suspected virulence factors (9)(10)(11), but also genes for toxic compound degradation (12,13) and heavy metal resistance (14). Several evolutionary distinct families of ICEs have been described, which have a mechanistically similar lifestyle (4,6,15).…”

mentioning

confidence: 99%

Highly variable individual donor cell fates characterize robust horizontal gene transfer of an integrative and conjugative element

Delavat

Mitri

Pelet

et al. 2016

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

106

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Horizontal gene transfer is an important evolutionary mechanism for bacterial adaptation. However, given the typical low transfer frequencies in a bacterial population, little is known about the fate and interplay of donor cells and the mobilized DNA during transfer. Here we study transfer of an integrative and conjugative element (ICE) among individual live bacterial cells. ICEs are widely distributed mobile DNA elements that are different than plasmids because they reside silent in the host chromosome and are maintained through vertical descent. Occasionally, ICEs become active, excise, and transmit their DNA to a new recipient, where it is reintegrated. We develop a fluorescent tool to differentiate excision, transfer, and reintegration of a model ICE named ICEclc (for carrying the clc genes for chlorocatechol metabolism) among single Pseudomonas cells by using timelapse microscopy. We find that ICEclc activation is initiated in stationary phase cells, but excision and transfer predominantly occur only when such cells have been presented with new nutrients. Donors with activated ICE develop a number of different states, characterized by reduced cell division rates or growth arrest, persistence, or lysis, concomitant with ICE excision, and likely, ICE loss or replication. The donor cell state transitions can be described by using a stochastic model, which predicts that ICE fitness is optimal at low initiation rates in stationary phase. Despite highly variable donor cell fates, ICE transfer is remarkably robust overall, with 75% success after excision. Our results help to better understand ICE behavior and shed a new light on bacterial cellular differentiation during horizontal gene transfer.

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Acquisition and Evolution of SXT-R391 Integrative Conjugative Elements in the Seventh-Pandemic Vibrio cholerae Lineage

Cited by 82 publications

References 54 publications

A λ Cro-Like Repressor Is Essential for the Induction of Conjugative Transfer of SXT/R391 Elements in Response to DNA Damage

A λ Cro-Like Repressor Is Essential for the Induction of Conjugative Transfer of SXT/R391 Elements in Response to DNA Damage

A globally distributed mobile genetic element inhibits natural transformation of Vibrio cholerae

Highly variable individual donor cell fates characterize robust horizontal gene transfer of an integrative and conjugative element

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