An inducible lambdoid prophage encoding cytolethal distending toxin (Cdt-I) and a type III effector protein in enteropathogenic
            <i>Escherichia coli</i>

Asakura, Masahiro; Hinenoya, Atsushi; Alam, Mohammad Samiul; Shima, Kensuke; Zahid, Shamim Hasan; Shi, Lei; Sugimoto, Norihiko; Ghosh, Avishek; Ramamurthy, T.; Faruque, Shah M.; Nair, G. Balakrish; Yamasaki, Shinji

doi:10.1073/pnas.0706695104

Cited by 58 publications

(67 citation statements)

References 29 publications

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“…E. coli is unique amongst CDTproducing bacteria in that at least five divergent variants of CdtB have been found within this single species so far, which also differentially segregate according to E. coli pathotypes ( Degnan & Moran, 2008). Indeed, carriage of the CDT operon by certain enteropathogenic E. coli with EcolCdtB-I on a lysogenic phage background mediates HGT among related species, and confers enhanced bacterial toxicity during phage induction (Asakura et al, 2007a;Johnson et al, 2007; Oswald et al, 1994; Pérès et al, 1997;Tó th et al, 2009). Also unique to E. coli is the location of the operon encoding EcolCdtB-III which is found on a large conjugative plasmid called pVir (Johnson et al, 2010).…”

Section: Cdt Operonmentioning

confidence: 99%

“…E. coli is unique amongst CDTproducing bacteria in that at least five divergent variants of CdtB have been found within this single species so far, which also differentially segregate according to E. coli pathotypes (Table 2; Janka et al, 2003). Since it is presently unknown whether or not the genes encoding the CdtA and CdtC subunits display sequence divergence similar to their corresponding CdtB variants, and until this can be resolved, we propose to designate these toxins as EcolCdtB-I to -V. Similar to other CDT-producing bacteria, EcolCdtB-I, -II, -IV and -V are encoded by chromosomal gene loci (Asakura et al, 2007a;Johnson et al, 2007;Oswald et al, 1994;Pérès et al, 1997;Tó th et al, 2009). However, analyses of sequences upstream and downstream of operons encoding EcolCdtB-I and -IV variants revealed lambdoid prophage genes (Asakura et al, 2007a;Tó th et al, 2009), whereas homologues of bacteriophages P2 and lambda are found in E. coli strain O157 : H 2 493/89 harbouring EcolCdtB-V (Janka et al, 2003).…”

Section: Cdt Operonmentioning

confidence: 99%

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Cytolethal distending toxin: a conserved bacterial genotoxin that blocks cell cycle progression, leading to apoptosis of a broad range of mammalian cell lineages

et al. 2011

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Cytolethal distending toxin (CDT) is a heterotrimeric AB-type genotoxin produced by several clinically important Gram-negative mucocutaneous bacterial pathogens. Irrespective of the bacterial species of origin, CDT causes characteristic and irreversible cell cycle arrest and apoptosis in a broad range of cultured mammalian cell lineages. The active subunit CdtB has structural homology with the phosphodiesterase family of enzymes including mammalian DNase I, and alone is necessary and sufficient to account for cellular toxicity. Indeed, mammalian cells treated with CDT initiate a DNA damage response similar to that elicited by ionizing radiationinduced DNA double strand breaks resulting in cell cycle arrest and apoptosis. The mechanism of CDT-induced apoptosis remains incompletely understood, but appears to involve both p53-dependent and -independent pathways. While epithelial, endothelial and fibroblast cell lines respond to CDT by undergoing arrest of cell cycle progression resulting in nuclear and cytoplasmic distension that precedes apoptotic cell death, cells of haematopoietic origin display rapid apoptosis following a brief period of cell cycle arrest. In this review, the ecology of pathogens producing CDT, the molecular biology of bacterial CDT and the molecular mechanisms of CDT-induced cytotoxicity are critically appraised. Understanding the contribution of a broadly conserved bacterial genotoxin that blocks progression of the mammalian cell cycle, ultimately causing cell death, should assist with elucidating disease mechanisms for these important pathogens. IntroductionJohnson and Lior's seminal observations in the 1980s identified a novel heat-labile toxin in culture filtrates obtained from certain Escherichia coli, Shigella dysenteriae and Campylobacter jejuni strains which caused distinctive and progressive cytoplasmic and nuclear enlargement of cultured mammalian cells, so called cytolethal distending toxin (CDT), and uncovered a novel paradigm amongst bacterial toxins and virulence mechanisms (Johnson & Lior, 1987, 1988a. It was not until many years later that Scott & Kaper (1994) identified the genes encoding CDT in E. coli, which set the stage for fundamental investigations into the ecology, biochemistry and molecular mechanisms of cellular toxicity associated with this novel bacterial toxin (Table 1). While a secreted protein cytotoxin was identified among Haemophilus (Haem.) ducreyi clinical isolates in the early 1990s by Purvén & Lagergård (1992), it was not until the late 1990s that this cytotoxin was conclusively shown to be encoded by a cdt gene cluster with homology to the previously identified E. coli genes (Cope et al., 1997). This discovery extended the range of niches where CDTproducing bacteria are found to include mucocutaneous surfaces of the genital tract in addition to the intestinal tract. At that time, Pérès et al. (1997) first reported that the mechanism of mammalian cell intoxication by E. coli CDT involved arrest of the cell cycle at the G2/M phase. Soon after, these observa...

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Section: Cdt Operonmentioning

confidence: 99%

“…E. coli is unique amongst CDTproducing bacteria in that at least five divergent variants of CdtB have been found within this single species so far, which also differentially segregate according to E. coli pathotypes (Table 2; Janka et al, 2003). Since it is presently unknown whether or not the genes encoding the CdtA and CdtC subunits display sequence divergence similar to their corresponding CdtB variants, and until this can be resolved, we propose to designate these toxins as EcolCdtB-I to -V. Similar to other CDT-producing bacteria, EcolCdtB-I, -II, -IV and -V are encoded by chromosomal gene loci (Asakura et al, 2007a;Johnson et al, 2007;Oswald et al, 1994;Pérès et al, 1997;Tó th et al, 2009). However, analyses of sequences upstream and downstream of operons encoding EcolCdtB-I and -IV variants revealed lambdoid prophage genes (Asakura et al, 2007a;Tó th et al, 2009), whereas homologues of bacteriophages P2 and lambda are found in E. coli strain O157 : H 2 493/89 harbouring EcolCdtB-V (Janka et al, 2003).…”

Section: Cdt Operonmentioning

confidence: 99%

Cytolethal distending toxin: a conserved bacterial genotoxin that blocks cell cycle progression, leading to apoptosis of a broad range of mammalian cell lineages

et al. 2011

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“…Epidemiological studies from elsewhere have detected only a low frequency of CLDTEC and an association of this toxin with EPEC or EHEC-linked serovars. The role of this toxin in human disease remains to be established and rather than a distinct category, CLDTEC may represent other pathotypes that are converted by lysogenization with a cdtbearing lambdoid phage [242].…”

Section: Other Potentially Diarrheagenic E Coli Categoriesmentioning

confidence: 99%

“…At least five different cytolethal distending toxins have been described in E. coli, and type I is phage borne [240][241][242]. Only two African studies have sought cytolethal distending toxinproducing E. coli (CLDTEC).…”

Section: Other Potentially Diarrheagenic E Coli Categoriesmentioning

confidence: 99%

Diarrheagenic Escherichia coli in sub-Saharan Africa: Status, Uncertainties and Necessities

Okeke

2009

J Infect Dev Ctries

125

103

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Diarrhea is a leading cause of illness and death, particularly in developing countries. Enteropathogenic Escherichia coli, enterotoxigenic E. coli (ETEC), enteroinvasive E. coli, enterohemorrhaghic E. coli (EHEC), enteroaggregative E. coli (EAEC) and diffusely adherent E. coli (DAEC) have been associated with diarrheal disease in different parts of Africa, particularly among young children, HIV-positive individuals, and visitors from abroad. Each of these E. coli pathotypes uses distinct mechanisms, which are only partially understood, to colonize infected hosts and produce diarrhea. All known diarrheagenic E. coli pathotypes have been reported from diverse locations within Africa but the true burden from these pathogens is unknown because very few studies seeking these organisms with discriminatory methodology have been performed. Recent reports implicate ETEC and EAEC in a considerable proportion of childhood and travellers' diarrheas and suggest that some sub-types of these categories may have greater epidemiological significance than others. The significant contribution of EHEC to bloody diarrhea and hemolytic uremic syndrome is underappreciated because diagnostic capacity for this pathotype is generally inferior to that for confounders such as Shigella and Entamoeba. Recent studies in Africa have revealed the worrisome emergence of antimicrobial resistance and high asymptomatic carriage rates for diarrheagenic E. coli but bacterial and host factors that predispose to disease, as well as non-human reservoirs, are largely unknown. Future diarrheal disease research needs to focus on broadening the repertoire of pathogens sought in epidemiological surveys to include multiple categories of diarrheagenic E. coli while building capacity to detect these pathogens in local reference laboratories.

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“…CDTs are quite disseminated in several species and so far in E. coli fi ve genotypes were identifi ed (reviewed by Tóth and Sváb) [7]. In all cases the cdtABC operons were either part of the genome of an inducible converting lambdoid prophage [8], a defective P-2 like prophage [9], a large plasmid [10], as part of a PAI [11] or framed with lambdoid phage genes [12].…”

Section: Introductionmentioning

confidence: 99%

The cytolethal distending toxin-IV cdt coding region in an avian pathogenic Escherichia coli (APEC) strain shows instability and irregular excision pattern

Tóth

Schneider

2015

Acta Microbiologica et Immunologica Hungarica

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Cytolethal distending toxins (CDT) represent an emerging toxin family, widely distributed among pathogenic bacteria. The cdtABC genes in E. coli are either part of the genome of prophages, plasmid or pathogenicity island. In order to investigate the stability and the transfer potential of cdt-IV genes cdtB gene was replaced by chloramphenicol (Cm) resistance encoding cat gene in the avian pathogenic E. coli (APEC) strain E250. After consecutive passages in non-selective medium at 37 °C 7.6% (219/2900) of the investigated colonies of E250::cat strain became Cm-sensitive (Cm S ). To reveal deletion mechanism 177 Cm S colonies were investigated for presence of cdtA, cdtC and cdtC associated gene by PCR. One hundred and sixteen colonies of the Cm S colonies (65.5%) showed partial or complete deletion in the cdt-IV region. Progressive loss of the upstream genes of the cdt cluster in E250 compared to other CDT-IV producing APEC strains and the fact that all the potential deletion patterns were identifi ed, suggests the presence of an unstable hitherto unknown genomic region. The failure of in vitro transfer of cdt genes into a porcine EPEC E. coli strain suggests that the deletion of cdt-IV fl anking genes alone do not promote the spread of cdt-IV.

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An inducible lambdoid prophage encoding cytolethal distending toxin (Cdt-I) and a type III effector protein in enteropathogenic Escherichia coli

Cited by 58 publications

References 29 publications

Cytolethal distending toxin: a conserved bacterial genotoxin that blocks cell cycle progression, leading to apoptosis of a broad range of mammalian cell lineages

Cytolethal distending toxin: a conserved bacterial genotoxin that blocks cell cycle progression, leading to apoptosis of a broad range of mammalian cell lineages

Diarrheagenic Escherichia coli in sub-Saharan Africa: Status, Uncertainties and Necessities

The cytolethal distending toxin-IV cdt coding region in an avian pathogenic Escherichia coli (APEC) strain shows instability and irregular excision pattern

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