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James B Kaper - One of the best experts on this subject based on the ideXlab platform.
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espc Pathogenicity Island of enteropathogenic escherichia coli encodes an enterotoxin
Infection and Immunity, 2001Co-Authors: Jay L Mellies, Fernando Navarrogarcia, Iruka N Okeke, Julie Frederickson, James P Nataro, James B KaperAbstract:At least five proteins are secreted extracellularly by enteropathogenic Escherichia coli (EPEC), a leading cause of infant diarrhea in developing countries. However only one, EspC, is known to be secreted independently of the type III secretion apparatus encoded by genes located within the 35.6-kb locus of enterocyte effacement Pathogenicity Island. EspC is a member of the autotransporter family of proteins, and the secreted portion of the molecule is 110 kDa. Here we determine that the espC gene is located within a second EPEC Pathogenicity Island at 60 min on the chromosome of E. coli. We also show that EspC is an enterotoxin, indicated by rises in short-circuit current and potential difference in rat jejunal tissue mounted in Ussing chambers. In addition, preincubation with antiserum against the homologous Pet enterotoxin of enteroaggregative E. coli eliminated EspC enterotoxin activity. Like the EAF plasmid, the espC Pathogenicity Island was found only in a subset of EPEC, suggesting that EspC may play a role as an accessory virulence factor in some but not all EPEC strains.
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a bacteriophage encoding a Pathogenicity Island a type iv pilus and a phage receptor in cholera bacteria
Nature, 1999Co-Authors: David K R Karaolis, Sita Somara, David R Maneval, Judith A Johnson, James B KaperAbstract:The virulence properties of many pathogenic bacteria are due to proteins encoded by large gene clusters called Pathogenicity Islands1,2, which are found in a variety of human pathogens including Escherichia coli, Salmonella, Shigella, Yersinia, Helicobacter pylori, Vibrio cholerae, and animal and plant pathogens such as Dichelobacter nodosus and Pseudomonas syringae1,2,3. Although the presence of Pathogenicity Islands is a prerequisite for many bacterial diseases, little is known about their origins or mechanism of transfer into the bacterium. The bacterial agent of epidemic cholera, Vibrio cholerae , contains a bacteriophage known as cholera-toxin phage (CTXφ)4, which encodes the cholera toxin, and a large Pathogenicity Island called the VPI (for V. cholerae Pathogenicity Island)5 which itself encodes a toxin-coregulated pilus that functions as a colonization factor6 and as a CTXφ receptor4. We have now identified the VPI Pathogenicity Island as the genome of another filamentous bacteriophage, VPIφ. We show that VPIφ is transferred between V. cholerae strains and provide evidence that the TcpA subunit of the toxin-coregulated type IV pilus is in fact a coat protein of VPIφ. Our results are the first description of a phage that encodes a receptor for another phage and of a virus–virus interaction that is necessary for bacterial Pathogenicity.
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a vibrio cholerae Pathogenicity Island associated with epidemic and pandemic strains
Proceedings of the National Academy of Sciences of the United States of America, 1998Co-Authors: David K R Karaolis, James B Kaper, Judith A Johnson, Camella C Bailey, Edgar C Boedeker, Peter R ReevesAbstract:The bacterial species Vibrio cholerae includes harmless aquatic strains as well as strains capable of causing epidemics and global pandemics of cholera. While investigating the relationship between pathogenic and nonpathogenic strains, we identified a chromosomal Pathogenicity Island (PAI) that is present in epidemic and pandemic strains but absent from nonpathogenic strains. Initially, two ToxR-regulated genes (aldA and tagA) were studied and were found to be associated with epidemic and pandemic strains but absent in nontoxigenic strains. The region containing aldA and tagA comprises 13 kb of previously unidentified DNA and is part of a PAI that contains a regulator of virulence genes (ToxT) and a gene cluster encoding an essential colonization factor and the cholera toxin phage receptor (toxin-coregulated pilus; TCP). The PAI is 39.5 kb in size, has low %G+C (35%), contains putative integrase and transposase genes, is flanked by att sites, and inserts near a 10Sa RNA gene (ssrA), suggesting it may be of bacteriophage origin. We found this PAI in two clinical non-O1/non-O139 cholera toxin-positive strains, suggesting that it can be transferred within V. cholerae. The sequence within this PAI includes an ORF with homology to a gene associated with the type IV pilus gene cluster of enteropathogenic Escherichia coli, a transposase from Vibrio anguillarum, and several ORFs with no known homology. As the PAI contains the CTXΦ receptor, it may represent the initial genetic factor required for the emergence of epidemic and pandemic cholera. We propose to call this Island VPI (V. cholerae Pathogenicity Island).
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A cloned Pathogenicity Island from enteropathogenic Escherichia coli confers the attaching and effacing phenotype on E. coli K‐12
Molecular microbiology, 1997Co-Authors: Timothy K. Mcdaniel, James B KaperAbstract:Attaching and effacing (AE) bacteria are a diverse group of gastrointestinal pathogens, comprising members of four genera, that cause the intestinal epithelial microvilli to be replaced with raised clusters of filamentous actin that conform to the surface of attached bacteria. We have cloned a 35.4 kb ‘Pathogenicity Island’ from the prototype AE bacterium, enteropathogenic Escherichia coli, containing all previously described AE genes. Transfer of this Pathogenicity Island to avirulent E. coli converts the recipients into strains that secrete virulence proteins, induce host signal-transduction pathways, and cause AE lesions on cultured epithelial cells. These results demonstrate that this Pathogenicity Island contains all pathogen-specific genes necessary for inducing AE lesions, and that the defining feature of this class of pathogens can be acquired by an avirulent bacterium in a single genetic step.
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a cloned Pathogenicity Island from enteropathogenic escherichia coli confers the attaching and effacing phenotype on e coli k 12
Molecular Microbiology, 1997Co-Authors: Timothy K. Mcdaniel, James B KaperAbstract:Attaching and effacing (AE) bacteria are a diverse group of gastrointestinal pathogens, comprising members of four genera, that cause the intestinal epithelial microvilli to be replaced with raised clusters of filamentous actin that conform to the surface of attached bacteria. We have cloned a 35.4 kb ‘Pathogenicity Island’ from the prototype AE bacterium, enteropathogenic Escherichia coli, containing all previously described AE genes. Transfer of this Pathogenicity Island to avirulent E. coli converts the recipients into strains that secrete virulence proteins, induce host signal-transduction pathways, and cause AE lesions on cultured epithelial cells. These results demonstrate that this Pathogenicity Island contains all pathogen-specific genes necessary for inducing AE lesions, and that the defining feature of this class of pathogens can be acquired by an avirulent bacterium in a single genetic step.
Elisabeth Carniel - One of the best experts on this subject based on the ideXlab platform.
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The Yersinia high-Pathogenicity Island
International Microbiology, 2010Co-Authors: Elisabeth CarnielAbstract:A Pathogenicity Island present only in highly pathogenic strains of Yersinia (Y. enterocolitica 1B, Y. pseudotuberculosis I and Y. pestis) has been identified on the chromosome of Yersinia spp. and has been designated High- Pathogenicity Island (HPI). The Yersinia HPI carries a cluster of genes involved in the biosynthesis, transport and regulation of the siderophore yersiniabactin. The major function of this Island is thus to acquire iron molecules essential for in vivo bacterial growth and dissemination. The presence of an integrase gene and att sites homologous to those of phage P4, together with a G + C content much higher than the chromosomal background, suggests that the HPI is of foreign origin and has been acquired by chromosomal integration of a phage. The HPI can excise from the chromosome of Y. pseudotuberculosis and is found inserted into any of the three copies of the asn tRNA loci present in this species. A unique characteristic of the HPI is its wide distribution in various enterobacteria. Although first identified in Yersinia spp., it has subsequently been detected in other genera such as E. coli, Klebsiella and Citrobacter
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The High-Pathogenicity Island Is Absent in Human Pathogens of Salmonella enterica Subspecies I but Present in Isolates of Subspecies III and VI
Journal of bacteriology, 2003Co-Authors: Tobias A. Oelschlaeger, Sören Schubert, D. Zhang, Elisabeth Carniel, Wolfgang Rabsch, Helge Karch, Jörg HackerAbstract:In this study we tested 74 Salmonella strains of all eight Salmonella groups and were able to demonstrate the presence of two high-Pathogenicity Island types in strains of Salmonella groups IIIa, IIIb, and VI. Most high-Pathogenicity Island-positive isolates produced yersiniabactin under iron-limited conditions and were positive for the high-molecular-weight proteins HMWP1 and HMWP2.
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The Yersinia high-Pathogenicity Island: an iron-uptake Island.
Microbes and infection, 2001Co-Authors: Elisabeth CarnielAbstract:Highly pathogenic Yersinia carry a Pathogenicity Island termed high-Pathogenicity Island (HPI). The Yersinia HPI comprises genes involved in the synthesis of the siderophore yersiniabactin and can thus be regarded as an iron-uptake Island. A unique characteristic of the HPI is its wide distribution among different enterobacteria such as Escherichia coli, Klebsiella, Citrobacter and Salmonella. Other types of iron-uptake systems are also carried by different Pathogenicity Islands in enterobacteria.
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The Yersinia high-Pathogenicity Island is present in different members of the family Enterobacteriaceae
FEMS microbiology letters, 2000Co-Authors: Sandrine Bach, Alzira Maria Paiva De Almeida, Elisabeth CarnielAbstract:A Pathogenicity Island termed high-Pathogenicity Island (HPI) is present in pathogenic Yersinia. This 35 to 45 kb Island carries genes involved in synthesis, regulation and transport of the siderophore yersiniabactin. Recently, the HPI was also detected in various strains of Escherichia coli. In this study, the distribution of the HPI in the family Enterobacteriaceae was investigated. Among the 67 isolates pertaining to 18 genera and 52 species tested, nine (13.4%) harbored the Island. These isolates were three E. coli, one Citrobacter diversus and five Klebsiella of various species (Klebsiella pneumoniae, Klebsiella rhinoscleromatis, Klebsiella ozaenae, Klebsiella planticola, and Klebsiella oxytoca). As in Yersinia sp., all nine isolates synthesized the HPI-encoded iron-repressible proteins HMWP1 and HMWP2. In the K. oxytoca strain, the right-end portion of the HPI was deleted, whereas the entire core region of the Island was present in the eight other enterobacteria strains analyzed. In most of these isolates, the HPI was bordered by an asn tRNA locus, as in Yersinia sp. This report thus demonstrates the spread of the HPI among various members of the family Enterobacteriaceae.
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prevalence of the high Pathogenicity Island of yersinia species among escherichia coli strains that are pathogenic to humans
Infection and Immunity, 1998Co-Authors: S. Schubert, Alexander Rakin, Elisabeth Carniel, H Karch, Jürgen HeesemannAbstract:The fyuA-irp gene cluster contributes to the virulence of highly pathogenic Yersinia (Yersinia pestis, Yersinia pseudotuberculosis, and Yersinia enterocolitica 1B). The cluster encodes an iron uptake system mediated by the siderophore yersiniabactin and reveals features of a Pathogenicity Island. Two evolutionary lineages of this “high Pathogenicity Island” (HPI) can be distinguished on the basis of DNA sequence comparison: a Y. pestis group and a Y. enterocolitica group. In this study we demonstrate that the HPI of the Y. pestis evolutionary group is disseminated among species of the family Enterobacteriaceae which are pathogenic to humans. It prevails in enteroaggregative Escherichia coli and in E. coli blood culture isolates (93 and 80%, respectively), but is rarely found in enteropathogenic E. coli, enteroinvasive E. coli, and enterotoxigenic E. coli isolates. In contrast, the HPI was absent from enterohemorrhagic E. coli, Shigella, and Salmonella enterica strains investigated. Polypeptides encoded by the fyuA, irp1, and irp2 genes located on the HPI could be detected in E. coli strains pathogenic to humans. However, these E. coli strains showed a reduced sensitivity to the bacteriocin pesticin, whose uptake is mediated by the FyuA receptor. Escherichia strains do not possess the hms gene locus thought to be a part of the HPI of Y. pestis. Deletions of the fyuA-irp gene cluster affecting solely the fyuA part of the HPI were identified in 3% of the E. coli strains tested. These results suggest horizontal transfer of the HPI between Y. pestis and some pathogenic E. coli strains.
Eduardo A. Groisman - One of the best experts on this subject based on the ideXlab platform.
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Control of Salmonella Pathogenicity Island-2 gene expression.
Current opinion in microbiology, 2009Co-Authors: Ephraim Fass, Eduardo A. GroismanAbstract:The Salmonella Pathogenicity Island-2 (i.e. SPI-2) encodes a unique type III secretion system that delivers effector proteins from the Salmonella-containing vacuole (SCV) into the host cell. The SPI-2 locus also encodes translocated effectors as well as a two-component system - termed SpiR/SsrB - that is essential for the expression of SPI-2 genes. Transcription of the horizontally acquired SPI-2 genes requires the ancestral nucleoid-associated proteins (i.e. NAPs) IHF and Fis, the regulatory protein SlyA, and the two-component systems PhoP/PhoQ and OmpR/EnvZ, as well as the DNA binding protein HilD encoded in a different Pathogenicity Island. Some of these positive SPI-2 regulators act to antagonize the robust silencing promoted by the NAPs H-NS, Hha, and YdgT.
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The SPI-3 Pathogenicity Island of Salmonella enterica
Journal of bacteriology, 1999Co-Authors: Anne-béatrice Blanc-potard, Felix Solomon, Jayson Kayser, Eduardo A. GroismanAbstract:Pathogenicity Islands are chromosomal clusters of pathogen-specific virulence genes often found at tRNA loci. We have determined the molecular genetic structure of SPI-3, a 17-kb Pathogenicity Island located at the selC tRNA locus of Salmonella enterica serovar Typhimurium. The G+C content of SPI-3 (47.5%) differs from that of the Salmonella genome (52%), consistent with the notion that these sequences have been horizontally acquired. SPI-3 harbors 10 open reading frames organized in six transcriptional units, which include the previously described mgtCB operon encoding the macrophage survival protein MgtC and the Mg2+ transporter MgtB. Among the newly identified open reading frames, one exhibits sequence similarity to the ToxR regulatory protein of Vibrio cholerae and one is similar to the AIDA-I adhesin of enteropathogenic Escherichia coli. The distribution of SPI-3 sequences varies among the salmonellae: the right end of the Island, which harbors the virulence gene mgtC, is present in all eight subspecies of Salmonella; however, a four-gene cluster at the center of SPI-3 is found in only some of the subspecies and is bracketed by remnants of insertion sequences, suggesting a multistep process in the evolution of SPI-3 sequences.
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The selC-associated SHI-2 Pathogenicity Island of Shigella flexneri.
Molecular microbiology, 1999Co-Authors: Jeremy E. Moss, Timothy Cardozo, Arturo Zychlinsky, Eduardo A. GroismanAbstract:Pathogenicity Islands are chromosomal gene clusters, often located adjacent to tRNA genes, that encode virulence factors present in pathogenic organisms but absent or sporadically found in related non-pathogenic species. The selC tRNA locus is the site of integration of different Pathogenicity Islands in uropathogenic Escherichia coli, enterohaemorrhagic E. coli and Salmonella enterica. We show here that the selC locus of Shigella flexneri, the aetiological agent of bacterial dysentery, also contains a Pathogenicity Island. This Pathogenicity Island, designated SHI-2 (ShigellaIsland 2), occupies 23.8 kb downstream of selC and contains genes encoding the aerobactin iron acquisition siderophore system, colicin V immunity and several novel proteins. Remnants of multiple mobile genetic elements are present in SHI-2. SHI-2-hybridizing sequences were detected in all S. flexneri strains tested and parts of the Island were also found in other Shigella species. SHI-2 may allow Shigella survival in stressful environments, such as those encountered during infection.
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identification of a Pathogenicity Island required for salmonella survival in host cells
Proceedings of the National Academy of Sciences of the United States of America, 1996Co-Authors: Howard Ochman, Felix Solomon, Fernando C Soncini, Eduardo A. GroismanAbstract:Abstract We have identified a region unique to the Salmonella typhimurium chromosome that is essential for virulence in mice. This region harbors at least three genes: two (spiA and spiB) encode products that are similar to proteins found in type III secretion systems, and a third (spiR) encodes a putative regulator. A strain with a mutation in spiA was unable to survive within macrophages but displayed wild-type levels of epithelial cell invasion. The culture supernatants of the spi mutants lacked a modified form of flagellin, which was present in the supernatant of the wild-type strain. This suggests that the Spi secretory apparatus exports a protease, or a protein that can alter the activity of a secreted protease. The "Pathogenicity Island" harboring the spi genes may encode the virulence determinants that set Salmonella apart from other enteric pathogens.
Jürgen Heesemann - One of the best experts on this subject based on the ideXlab platform.
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The High-Pathogenicity Island of Yersiniae
Pathogenicity Islands and Other Mobile Virulence Elements, 2014Co-Authors: Alexander Rakin, Sören Schubert, Daniela Brem, Cosima Pelludat, Jürgen HeesemannAbstract:Yersinia species are gram-negative rods that belong to the family of Enterobacteriaceae. According to biochemical and metabolic characteristics, DNA-DNA hybridization, and 16S rRNA sequencing results, the genus Yersinia comprises 11 different species. Yersinia pestis, Yersinia pseudotuberculosis, and Yersinia enterocolitica are pathogens for humans, and Yersinia ruckeri is known as a fish pathogen. Y. pestis, the bacterial agent of bubonic plague, has been responsible for devastating epidemics throughout human history. This pathogen persists among certain wild rodent populations in many parts of the world (except Australia) and is transmitted by the bite of infected fleas. Deletion of a 102-kb chromosomal pgm fragment that results in nonpigmented yersiniae might be mediated by homologous recombination between two IS700 sequences flanking the pgm locus. Such instability of the 102- kb chromosomal fragment, which is associated with virulence of Y. pestis, was the reason for denoting it a Pathogenicity Island. Survival and proliferation within the host depend on the ability of a pathogen to scavenge essential nutrients such as iron, which is bound by the host molecules ferritin, transferrin, and lactoferrin. The fyuA promoter contains a consensus Fur iron-repressor binding site and a putative binding site for the yersiniabactin AraC-type transcriptional regulator YbtA. Recently, the high-Pathogenicity Island (HPI) was detected in other members of the family Enterobacteriaceae, e.g., in variety of pathotypes of Escherichia coli, Klebsiella, Enterobacter, and Citrobacter.
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Transcriptional regulation of high Pathogenicity Island iron uptake genes by YbtA
International journal of medical microbiology : IJMM, 2005Co-Authors: Roman Anisimov, Jürgen Heesemann, Daniela Brem, Alexander RakinAbstract:A large group of Enterobacteriaceae, including members of the genus Yersinia, produce the extracellular siderophore yersiniabactin enabling them to multiply under iron-depleted conditions. Genes, involved in yersiniabactin synthesis, transport and regulation are clustered in the high Pathogenicity Island (HPI). YbtA, an AraC-like transcriptional regulator, is presumed to be the central regulator of yersiniabactin production together with the ferric uptake regulator Fur. In this work, we identified the transcriptional start points of YbtA-regulated promoters of the HPI by primer extension, purified homogeneous YbtA and defined the YbtA-binding sites by DNaseI footprint analysis in ybtA, fyuA, irp6, and irp2 promoters. Besides of the anticipated pair repeats RS1 and RS2 in each promoter, we identified an additional YbtA-binding site designated RS3 in the divergently transcribed ybtA/irp6 promoter. Also, comparing ybtA/irp6 promoters of Y. enterocolitica and Y. pestis, we found that a 125-bp ERIC element insertion in the RS2 sequence of the Y. enterocolitica ybtA/irp6 promoter might increase YbtA expression, but did not affect expression of Irp6.
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Integrative module of the high-Pathogenicity Island of Yersinia
Molecular microbiology, 2001Co-Authors: Alexander Rakin, C. Noelting, P. Schropp, Jürgen HeesemannAbstract:The high-Pathogenicity Island of Yersinia pestis (Yps HPI) encodes virulence-associated genes involved in siderophore yersiniabactin-mediated iron uptake. The Yps HPI contains a P4-type integrase (Int-HPI), associated with the asn-tRNA locus, and is flanked by 17 bp direct repeats. We constructed a minimal integrative module of the Pathogenicity Island carrying the reconstituted 266 bp attP (POP′) attachment site derived from putative attR and attL junctions of the Yps HPI and the functional int-HPI gene from Y. pestis KUMA. The attP–int-HPI module recombined efficiently, site specifically and RecA independently with the bacterial attB site present either in the chromosome (asn-tDNA) or on a plasmid, with no preference for a certain asn-tRNA gene. The excision of the integrated suicide plasmid carrying the integrative module, on the other hand, was a rare event and could be demonstrated only by polymerase chain reaction. Analysis of the 5′ terminus of the transcript for int-HPI revealed that the integration of attP–int-HPI was coupled with the replacement of the endogenous int-HPI promoter, localized in the P′ part of the attP site, by the adjacent asn-tRNA promoter. These results suggest that two alternative promoters control integration and excision of the HPI by its integrase.
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prevalence of the high Pathogenicity Island of yersinia species among escherichia coli strains that are pathogenic to humans
Infection and Immunity, 1998Co-Authors: S. Schubert, Alexander Rakin, Elisabeth Carniel, H Karch, Jürgen HeesemannAbstract:The fyuA-irp gene cluster contributes to the virulence of highly pathogenic Yersinia (Yersinia pestis, Yersinia pseudotuberculosis, and Yersinia enterocolitica 1B). The cluster encodes an iron uptake system mediated by the siderophore yersiniabactin and reveals features of a Pathogenicity Island. Two evolutionary lineages of this “high Pathogenicity Island” (HPI) can be distinguished on the basis of DNA sequence comparison: a Y. pestis group and a Y. enterocolitica group. In this study we demonstrate that the HPI of the Y. pestis evolutionary group is disseminated among species of the family Enterobacteriaceae which are pathogenic to humans. It prevails in enteroaggregative Escherichia coli and in E. coli blood culture isolates (93 and 80%, respectively), but is rarely found in enteropathogenic E. coli, enteroinvasive E. coli, and enterotoxigenic E. coli isolates. In contrast, the HPI was absent from enterohemorrhagic E. coli, Shigella, and Salmonella enterica strains investigated. Polypeptides encoded by the fyuA, irp1, and irp2 genes located on the HPI could be detected in E. coli strains pathogenic to humans. However, these E. coli strains showed a reduced sensitivity to the bacteriocin pesticin, whose uptake is mediated by the FyuA receptor. Escherichia strains do not possess the hms gene locus thought to be a part of the HPI of Y. pestis. Deletions of the fyuA-irp gene cluster affecting solely the fyuA part of the HPI were identified in 3% of the E. coli strains tested. These results suggest horizontal transfer of the HPI between Y. pestis and some pathogenic E. coli strains.
David K R Karaolis - One of the best experts on this subject based on the ideXlab platform.
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a bacteriophage encoding a Pathogenicity Island a type iv pilus and a phage receptor in cholera bacteria
Nature, 1999Co-Authors: David K R Karaolis, Sita Somara, David R Maneval, Judith A Johnson, James B KaperAbstract:The virulence properties of many pathogenic bacteria are due to proteins encoded by large gene clusters called Pathogenicity Islands1,2, which are found in a variety of human pathogens including Escherichia coli, Salmonella, Shigella, Yersinia, Helicobacter pylori, Vibrio cholerae, and animal and plant pathogens such as Dichelobacter nodosus and Pseudomonas syringae1,2,3. Although the presence of Pathogenicity Islands is a prerequisite for many bacterial diseases, little is known about their origins or mechanism of transfer into the bacterium. The bacterial agent of epidemic cholera, Vibrio cholerae , contains a bacteriophage known as cholera-toxin phage (CTXφ)4, which encodes the cholera toxin, and a large Pathogenicity Island called the VPI (for V. cholerae Pathogenicity Island)5 which itself encodes a toxin-coregulated pilus that functions as a colonization factor6 and as a CTXφ receptor4. We have now identified the VPI Pathogenicity Island as the genome of another filamentous bacteriophage, VPIφ. We show that VPIφ is transferred between V. cholerae strains and provide evidence that the TcpA subunit of the toxin-coregulated type IV pilus is in fact a coat protein of VPIφ. Our results are the first description of a phage that encodes a receptor for another phage and of a virus–virus interaction that is necessary for bacterial Pathogenicity.
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a vibrio cholerae Pathogenicity Island associated with epidemic and pandemic strains
Proceedings of the National Academy of Sciences of the United States of America, 1998Co-Authors: David K R Karaolis, James B Kaper, Judith A Johnson, Camella C Bailey, Edgar C Boedeker, Peter R ReevesAbstract:The bacterial species Vibrio cholerae includes harmless aquatic strains as well as strains capable of causing epidemics and global pandemics of cholera. While investigating the relationship between pathogenic and nonpathogenic strains, we identified a chromosomal Pathogenicity Island (PAI) that is present in epidemic and pandemic strains but absent from nonpathogenic strains. Initially, two ToxR-regulated genes (aldA and tagA) were studied and were found to be associated with epidemic and pandemic strains but absent in nontoxigenic strains. The region containing aldA and tagA comprises 13 kb of previously unidentified DNA and is part of a PAI that contains a regulator of virulence genes (ToxT) and a gene cluster encoding an essential colonization factor and the cholera toxin phage receptor (toxin-coregulated pilus; TCP). The PAI is 39.5 kb in size, has low %G+C (35%), contains putative integrase and transposase genes, is flanked by att sites, and inserts near a 10Sa RNA gene (ssrA), suggesting it may be of bacteriophage origin. We found this PAI in two clinical non-O1/non-O139 cholera toxin-positive strains, suggesting that it can be transferred within V. cholerae. The sequence within this PAI includes an ORF with homology to a gene associated with the type IV pilus gene cluster of enteropathogenic Escherichia coli, a transposase from Vibrio anguillarum, and several ORFs with no known homology. As the PAI contains the CTXΦ receptor, it may represent the initial genetic factor required for the emergence of epidemic and pandemic cholera. We propose to call this Island VPI (V. cholerae Pathogenicity Island).