| Nucleic Acids Research | Pages |
The complete DNA sequence and analysis of the large virulence plasmid of Escherichia coli O157:H7
Introduction
Materials And Methods
Sequencing of pO157
Annotation
Results And Discussion
Organization and physical properties
New putative virulence gene
Previously sequenced virulence genes
General secretory pathway
Other putative proteins
Replication regions and plasmid maintenance
Transfer region
Insertion sequence elements
Tn801
Phylogeny
Base distribution
Acknowledgements
References
The complete DNA sequence and analysis of the large virulence plasmid of Escherichia coli O157:H7
DDBJ/EMBL/GenBank accession nos AF074613 and AF080442
ABSTRACT
INTRODUCTION
Enterohemorrhagic Escherichia coli (EHEC) O157:H7 strains are the predominant causative agent of hemorrhagic colitis, a bloody diarrhea which can lead to potentially lethal renal failure in hemolytic-uremic syndrome (HUS) (1,2). EHEC have become increasingly recognized as an important public health concern world-wide since they were first implicated in these diseases in 1983. The Center for Disease Control and Prevention (CDC) currently estimate that O157:H7 causes 25 000 cases of illness with 100 deaths each year in the US alone (3), and new outbreaks are reported every few months. Some virulence determinants contributing to EHEC infections have been characterized, but clearly, a search for all the underlying genes of EHEC pathogenesis will be facilitated by complete DNA sequencing of the O157:H7 genome, now underway in this laboratory. Since the genome sequence of a benign strain, E.coli K-12 is known (4), we are in a position to discover the genetic factors that distinguish the pathogenic E.coli genome from the benign, keeping in mind that 'virulence' is multigenic, that determinants may act in concert to produce a pathogenic effect, and that benign strains may also encode parts of pathogenic pathways or mechanisms. Most of the Gram-negative pathogens contain plasmids, which frequently carry virulence determinants. In this paper we present the results of the first part of this project, the complete plasmid sequence.
EHEC infections are characterized by binding of the infecting bacteria to intestinal epithelial cells, inducing structural changes by disruption of actin organization. These changes, and production of the resulting lesions, are known as attachment and effacement, and occur in both EHEC and EPEC (enteropathogenic E.coli) infections (5,6; reviewed in 7,8). Several virulence factors contributing to pathogenesis have been identified, including Shiga-like toxins (SLTs) (9), and intimin, essential for the tight binding of bacteria to target cells (10). These genes are encoded on 'pathogenicity islands' (PAIs) in the O157 chromosome. In the case of the SLTII, the island is an integrated phage, 933W (11), and intimin is encoded by the LEE element (8,12), also thought to have been acquired by horizontal transfer from an outside source. The large plasmid pO157 is found in most EHEC O157:H7 strains. Its role in pathogenicity is not clearly defined, partly because of conflicting results from studies in various animal models, none of which consistently displays all the characteristics of infection in humans (7). Several reports do correlate pO157 with virulence, for example, with hemolytic activity (13), and adherence to intestinal cells (14,15). Some pO157 putative virulence genes have already been sequenced. A catalase-peroxidase (16), an extracellular serine protease (17), the four genes of the hemolysin locus (18), and 13 genes comprising a type II secretory system (19) have been reported, though the functions of the protease and the putative secretory system have not been examined. A heat stable enterotoxin, EAST1, is encoded by astA on the large plasmid of entero-aggregative E.coli where it was discovered. In O157:H7 strains, including EDL933, astA was found in two copies on the chromosome (20).
Obtaining the complete DNA sequence of the plasmid may help to raise the level of our understanding of the plasmid itself, and its roles in virulence and gene transfer. The sequence offers a catalog of the potential genes and the opportunity to identify new potential virulence determinants, and may point the way to experimental approaches that address the complexities of E.coli pathogenesis.
MATERIALS AND METHODS
Sequencing of pO157
The plasmid was was obtained in host C600 from R. A. Welch. It was initially isolated from EHEC O157:H7 strain EDL933 and marked for genetic experiments with the ampicillin-resistance transposon Tn801 from RP1 (13,15). It was known in this form as pSK3. To avoid confusion with other unrelated plasmids called pSK3, the name pO157 has been used here. The marker transposon (previously unsequenced) was included as part of the entire plasmid project, then spliced out of the finished pO157 sequence file and submitted to the database separately. The insertion point is included in the plasmid annotation file. Both the plasmid and the transposon sequences were deposited in GenBank, accession numbers AF074613 (pO157) and AF080442 (Tn801).
Sequences were initially collected from random library clones in a genomic library of O157:H7 EDL933 containing the natural plasmid unmarked by Tn801, and also from a library of purified pO157::Tn801 DNA. Libraries were prepared (21) in M13 Janus (22). DNA templates were purified from library clones (23) and sequences collected using dye-terminator labelled fluorescent cycle sequencing (Prism[trade] reagents and ABI377 automated sequencer; Applied Biosystem Division of Perkin-Elmer). After assembly into contigs using DNASTAR software, clones were selected for sequencing from the opposite end by the Janus method (22), followed by primer walking to close the last gap. The accuracy of the sequence is estimated at better than one error in 10 000 bases. Any errors persisting after rigorous efforts to detect and resolve frameshifts are most likely to be base substitutions.
Annotation
We identified the open reading frames (ORFs), promoters, operons, regulatory sites, mobile genetic elements and repeated sequences in the plasmid genome, using DNASTAR software and programs written in the laboratory (4). ORFs of at least 50 amino acids were selected from among all possible ORFs by a combination of codon usage analysis, database matches and presence of upstream elements such as promoter-like sequences and ribosome binding sites. Codon usage statistics were used in Geneplot or GeneQuest (DNASTAR) to help predict ORFs, with codon usage matrices developed by Borodovsky (24). Operons were predicted from the arrangement of ORFs and promoters and should be considered as putative. In the absence of any other information, the translation initiation codon giving the longest coding region was chosen, including GUG and UUG. The latter two codons are becoming more frequently validated, especially for genes that apparently have been horizontally transferred. The DNA sequence was searched against GenBank to identify non-coding features. ORF amino acid sequences were searched against SWISS-PROT 34 and GenPept 104 using the BLOSUM62 matrix and the Smith-Waterman algorithm accelerated by the DeCypher II system (TimeLogic Inc.) to assign known functions or suggest functions for new ORFs (4). The criteria for good matches to database entries for assignment of putative function were >30% similarity over >60% of each sequence. ORFs are labelled with numbers L7001-L7100, clockwise as shown on the map in Figure
Figure 1. Map of pO157, with small scale map of the F plasmid for comparison. Outer circle of pO157 represents scale in nt. Middle circle shows ORFs color coded for function as indicated by the key. Orientation of transcription is clockwise for the outer ORFs, counter-clockwise for the inner ORFs. Operons are indicated by arrows. Inner circle shows the inverse of the CAI score for each ORF, color coded so that unusually low scores are emphasized (light green). The F plasmid map is approximately scaled (not yet fully sequenced) and color coded for comparison with pO157. The genome of pO157-EDL933, shown in Figure We found 100 ORFs, most of them oriented in the same direction. Operon arrangements are indicated in Figure Analysis of base composition showed the G+C content of the plasmid to be significantly lower than in E.coli K-12, with A (26.74%), T (25.53%), C (21.97%) and G (25.73%), giving G+C as 47.7%. The rare palindromic tetramer, CTAG, found in K-12 strain MG1655 at only 5% of the frequency predicted from base composition (4) occurs at 8% of predicted frequency in pO157. A restriction map of the plasmid for seven enzymes (27) was compared with the map predicted from the complete sequence. Several BamHI, ClaI and EcoRI sites we found in the sequence were not observed by Schmidt et al. (27), but would have produced very small restriction fragments which could easily be lost on a mapping gel. Three other missing ClaI fragments are explained by dam methylase-sensitive sites. The only unexplained difference is that one of the two XbaI sites in the digest is not found in the sequence. It was reported several years ago that the intestinal lesions produced in O157:H7 colitis, and the toxin-mediated damage to intestinal cells in Clostridium difficile infections, are similar enough to confuse (28). It was suggested by these authors that O157:H7 toxins were responsible. Intriguingly, the most striking newly sequenced gene in pO157 is an unusually large ORF of 3169 amino acids (L7095) which shows strong sequence similarity in a BLAST search, within the first 700 residues, to the activity-containing N-terminal domain of a toxin family known as the large clostridial toxins (LCT) that includes ToxA (2710 amino acids) and ToxB (2366 amino acids) from C.difficile. The four known LCT proteins include Clostridium novyi alpha toxin (2178 amino acids) and Clostridium sordelli cytotoxin L (2364 amino acids) as well as the two Clostridium difficile proteins. These AB cytotoxins share a C-terminal domain that functions in toxin entry into the cell and an N-terminal glucosyltransferase that modifies G proteins such as rho, rac and ras, resulting in the altered regulation of the cytoskeleton, with these two fundamental domains separated by a proposed membrane spanning region. The glucosyltransferase activity of these LCT proteins has been demonstrated biochemically, but they have not been previously described as part of a known glycosyltransferase family based on sequence similarity (29-32). Strong similarity is also seen between the N-terminal domain of L7095 protein over the full extent of a 639 amino acids protein from Chlamydia trachomatis (gi¦3328569). A conserved motif from the OCH1 glycosyltransferase family was detected in the N-terminal domains of the L7095 protein and the four LCT toxins using Probe program which performs an iterative profile search (33) (Fig. Figure 2. A conserved motif is shared between L7095 and the LCT proteins and the OCH1 glycosyltransferase family. A Probe search of the nr database derived from GenBank (4.16.98) using the N-terminal domain of L7095 detected a conserved motif that is shared with the four known LCT proteins and the yeast OCH1 family. The sequences shown in the motif are identified by the following accession or GenInfo (gi) numbers and can be located using the SwissProt or GenBank databases: ToxA from C.difficile (sp¦P16154¦TOXA_CLODI); ToxB from C.difficile (sp¦P18177¦TOXB_CLODI); alpha-toxin from C.novyi (gi¦755724); cytotoxin L from C.sordellii (gi¦1000695); hypothetical protein from C.trachomatis gi¦3328569; OCH1 from Saccharomyces cerevisiae (sp¦P31755¦OCH1_YEAST¦); HOC1 from S.cerevisiae (sp¦P47124¦HOC1_YEAST); SUR1 from S.cerevisiae (sp¦P33300¦SUR1_YEAST); 44.4 kDa protein from S.cerevisiae (sp¦P38287¦YB11_YEAST); 42.2 kDa protein fromSchizosaccharomyces pombe (sp¦P10323¦YD6B_SCHPO); hypothetical protein from S.pombe (gi¦2408057); 21.6 kDa protein from Actinobacillus pleuropneumoniae (sp¦P46393¦YARQ_ACTPL). Both the OCH1 family and the toxin proteins show an absolutely conserved DXD pattern of aspartates in the motif. Highly conserved aspartate or glutamate residues are expected to be characteristic of glycosyltransferases (37). After submission of this manuscript, work was published showing these two aspartate residues to be essential for the enzymatic activity of the C.sordelli cytotoxin L (D286 and D288) (38). The region in the C.sordelli cytotoxin L between residues 364 and 516 has recently been shown to play an important role in determining the specificity of the small G protein substrate for the glycosylation reaction (39). These findings are entirely consistent with the putative function of L7095 as a cytotoxin. Prediction of transmembrane spanning domains using the PHD software on the PredictProtein server (40) showed a single membrane-spanning helix in each of the LCT proteins at ~1100 residues (CdA, 1075..1099; CdB, 1073..1098; CnA, 1081..1105; CsL, 1073..1097) and in the L7095 protein a single predicted transmembrane region is located at 1961..1980. In each case the putative transmembrane domain is contained within a larger region predicted by the Seg program to be non-globular in structure (41,42). In the clostridial proteins the putative transmembrane region is located within a low-complexity region of ~400 residues (CdA, 764..1134; CdB, 722..1131; CnA, 767..1186; CsL, 746..1131). The predicted transmembrane region in the L7095 protein is located within a smaller medium-complexity region of ~40 residues (1942..1981), but an additional low-complexity domain is seen upstream at 1659..1813. The sequence in the vicinity of L7095 was examined for regulatory elements. A putative promoter was found to overlap the first possible start codon, and the next upstream ORF, a transposase gene in the same orientation, has a good promoter which could conceivably read through L7095. Curiously, the strongest promoter consensus in the region (identical with the sigma 70 consensus sequence) was found in the middle of L7095 oriented with the ORF. No rho-independent transcription terminators were found. Codon usage by L7095 is more like that of genes of phages and mobile elements than E.coli genes, while the CAI (Fig. The plasmid-encoded hemolysin was the first pO157 sequence to be determined (X86087) (18,27). The term EHEC-hemolysin was used to distinguish it from alpha-hemolysin to which it is related but not identical. EHEC-hemolysin belongs to the RTX (repeats in toxin) family of exoproteins (43,44). Four gene products of the hlyCABD operon (L7047-L7050), encode a pore-forming cytolysin and its secretion apparatus. Toxicity results from the insertion of HlyA into the cytoplasmic membrane of the target mammalian cells disrupting permeability control (45). Our sequence of pO157 has several differences from the original determination (X86087) by Schmidt et al. (46). However, more recent determinations for hlyA, B and the 5[prime] part of hlyC (U12572 and Y09824) are in complete agreement with our sequence, including correction of a frameshift error at the start of hlyC. There are no other recent determinations for the plasmid-encoded hlyD, in which our sequence has four differences from X86087, three resulting in a different amino acid. The product of the tolC gene is also required for secretion of this toxin. In O157:H7 EDL933 TolC is encoded on the chromosome (preliminary data, this laboratory). An EHEC catalase-peroxidase is encoded on pO157 by katP (L7017) (16) (X89017), whose product is a bifunctional periplasmic enzyme that protects the bacterium against oxidative stress, one possible hazard of infecting mammalian cells. The occurrence of the katP gene in EHEC strains is associated with the EHEC hemolysin operon (16,17). Brunder et al. also located an extracellular serine protease gene, espP (L7020), on pO157 (X97542). EspP is homologous to EspC (U69128), a secreted protein of EPEC whose role in pathogenicity is unknown. The proteases are Type IV secreted proteins (autotransporters). A domain for effecting translocation across the cell membrane is encoded within the polypeptide. This protein belongs to a family of virulence factors that are secreted in this manner (47). Widely observed in O157 strains, its demonstrated ability to cleave human coagulation factor V probably exacerbates the epithelial degradation and hemorrhage resulting from EHEC infection. A gene cluster closely related to the type II secretion pathway of Gram-negative bacteria has recently been sequenced in pO157 (19); Y09824. The 13 genes of this operon, etpC through etpO (L7032-L7044), show a high degree of similarity to the genes of the general secretory pathway (GSP) in Klebsiella pnueumoniae (M32613), Aeromonas hydrophyla (X66504), Erwinia chrysanthemi (L02214) and Erwinia caratova (X70049), ranging from 40% to >90% identity over at least half of each gene. This pathway provides a mechanism of exoprotein secretion for these and other pathogenic Gram-negative bacteria (48,49). Although the operon appears to contain the necessary genes, its ability to secrete proteins has not yet been demonstrated, nor is its substrate known. Its correlation with disease is also unclear. Curiously, E.coli K-12 also has a chromosomally encoded GSP operon, though only two of its genes appear to be expressed in the laboratory strain (50). We have preliminary sequence data showing that this K-12 chromosomal operon is also present in the O157:H7 EDL933 genome. The similarities between the genome-encoded GSP and corresponding genes of the plasmid etp operon are in the range 15-60%, i.e. much lower than the matches to operons in other organisms; clearly this operon is more likely to have been acquired from outside than to have derived directly from the K-12 genome. We note that in Y09824, the translation starts chosen for EtpD, I, L and N are AUG codons giving shorter ORFs than those we defined. In these four cases we chose upstream in-frame GUG starts, since the amino acid sequence between the GUG and AUG codons showed a high degree of similarity with the homologous ORFs in Klebsiella or Erwinia; the similarity scores are, respectively, 65.5% over 57 amino acids, 50% over 6 amino acids, 33.1% over 143 amino acids and 53.9% over 39 amino acids. We found a homolog (L7004; 90% identity, full length alignment) of the E.coli regulator Hha, a modulator of hemolysin expression (P23870) (51). Of two ORFs encoded on opposite strands of the same DNA region, L7023 shows 85% similarity to 46 residues of an ORF that was originally identified as PerD (P43476) of EPEC strain E2348/69 (O127:H6). The per operon was shown to regulate expression of intimin, an essential factor in the attaching and effacing lesions of EHEC infection (52). The perD gene was also reported to show similarity to Tn7 and IS630 sequences, though our ORF does not. No role in regulation has been established for this gene, and a recent account of the per operon no longer shows the fourth gene (7). No other plasmid ORFs had any match to the other per products, and neither did the ORF on the opposite strand show any striking match. Downstream of the hemolysin operon, two adjacent ORFs showed ~50% similarity with 20 and 42 residues from different parts of a second E.coli regulator, PapX, that controls pilus production (P42193). The two ORFs (L7051 and L7052) represent parts of the gene separated by a frameshift. Pili are integral to the recognition and initial attachment of EHECs to the target cells. While there are no obvious pilus components encoded on pO157, two ORFs have some similarity to pilin-related proteins; one (L7081) shows 27% similarity over 67 residues to OrfQ (Q46527), of unidentified function in the fim operon of Bacteroides, and the second (L7024) shows 49% similarity to 43 amino acids in part of the fimbrial regulator FimB of E.coli (P04742). Two ORFs show similarity to proteins involved in cell membrane or its production. L7029 is 66% identical over 323 amino acids with MsbB, an E.coli acyltransferase (P24205). Though not acting on its normal substrate, this protein can take part in LPS production by substituting for HtrB, an acetyltransferase that adds the myristoyl fatty acid to lipid A (53). The myristate component of lipid A, which is the endotoxin portion of LPS, appears to activate and antagonize immune cells (54). L7092 has a region that is 34% similar over 77 amino acids to the functional domain of TolA (P19934), a membrane receptor in E.coli for colicins and filamentous phages, though the structural domains do not appear to be present. Two ORFs are similar to genes of Vibrio cholerae. A 324 amino acid segment of L7031 shows 43% identity to 131 amino acids of the C-terminal half of TagA of V.cholerae (Q56595). This is a lipoprotein regulated by ToxR (55), thought to be involved in fimbrial biosynthesis because of its similarity to FanD of E.coli K99 (P12050) (56), but not essential for virulence. The similarities between L7031, TagA and FanD do not overlap, and neither the signal peptide nor the lipid attachment site of TagA are found in L7031, so no function may be deduced. L7074 is 33% similar over 204 amino acids to hemagglutinin-associated protein in V.cholerae, whose function is unknown (Q56638). This pO157 ORF has a homolog in the large virulence plasmid pMT1 of Yersinia pestis (Lindler,L.E., Plano.G.V., Burland,V., Mayhew,G.F. and Blattner,F.R., submitted to Infect. Immunol.) suggesting a common function. However, both proteins also show similar identities to methylases of several organisms, so a virulence function cannot yet be assigned. In summary, 19 of the 100 ORFs on the plasmid have confirmed functions, 42 may be assigned putative functions on the basis of their database matches, and 17 have good matches to hypothetical genes in the database. The remaining 22 ORFs had only poor matches to database entries and cannot be assigned functions with any confidence. Three possible replication origins were found, their structures consistent with pO157 belonging to the incFII group of F plasmids (57,58). In Figure Figure 3. (A) Comparison of the RepFIA regions of pO157 and the F plasmid. Deletions are represented by [ ]. In pO157, IS629 replaces incB and the N-terminus of the protein E gene, and part of incD is deleted. (B) Comparison of the RepFIB regions of pO157 and p307. Short vertical lines represent repeats. 209 bp are deleted from the left end of the minimum replication region, but all the repeats required for function are present. The second replication origin is 97% similar to the RepFIB replicon region of the enterotoxinogenic (incFI) plasmid p307 (M26308) (60), which differs by only a few bases from that of the F plasmid (61). RepFIB is conserved as a functional replicon in most of the incF plasmids (62). A pO157 ORF (L7056) in this region is 99% identical to an essential replication protein Orf1 of p307 (gi¦516615). By comparison with the essential replication region of p307, the 'rep' region of pO157 includes all the essential repeats (BCD and EFG), but lacks 209 bp at the left end (Fig. The third replication origin in pO157 corresponds to the RepFIA region of the F plasmid. It is disrupted in pO157 by insertion of IS629 (Fig. pO157 was known to be non-conjugative (57). In comparision with F (Fig. pO157 contains several insertion sequence (IS) elements and related sequences at seven different loci, shown in Figure Table 1. This ampicillin resistance transposon is closely related to Tn3. On insertion, the 5 bp target site TTATA, different from the Tn3 target, is duplicated as a direct repeat. The 4949 bp element is 8 bp shorter than Tn3 (68), and 97.7% similar across the whole element at the nucleotide level. Inverted repeats of 38 bp are at each end, with three genes encoded in between, a transposase (tnpA), the ampicillin resistance ([beta]-lactamase, bla) and a repressor (tnpR), showing the same organization as Tn3. The transposase is 14 amino acids shorter at the N-terminus than the Tn3 protein, the repressor is identical, and [beta]-lactamase is 99% identical. The internal resolution site in the N-terminal portion of tnpA is intact and differs from the Tn3 site by only two out of 23 bp. The site also contains 18 bp identical to a part of the inverted repeats, compared with 19 bp for Tn3 (69). Boyd et al. (26) have suggested that the genes of plasmids are more heterogeneous than those of the chromosome, as a result of higher rates of recombination, and frequent plasmid transfer. To understand the relationship between pO157 and other F-like plasmids, and place pO157 in the phylogenic trees constructed by Boyd, we compared their RepA and FinO sequences. The proteins of pO157 were aligned with previously published homologs from F-like plasmids in reference collections of E.coli (ECOR) and Salmonella (SARA) strains (26,70). Phylogenetic trees, shown in Figure Figure 4. Phylogenetic trees show the relationships among SARA (Salmonella) and ECOR (E.coli) strains (see text) for RepA and FinO sequences from the F-like plasmids of these strains. Alignments were made by MegAlign (DNASTAR) and the phylogeny was reconstructed by MEGA (75). Genetic distances are maximum likelihood estimates of the number of nucleotide substitutions between two sequences, corrected for multiple substitutions. The numbers shown along the branches indicate the percentage of 2000 bootstrap replicates supporting each cluster. The alignments are available for inspection on request. The analysis of base distribution revealed two notably AT-rich regions. A 7.7 kb region of 62.6% A+T corresponded to the genes of the hemolysin operon with the adjacent broken reading frames of papX. A second region, 9.5 kb of 68.6% A+T, corresponded to ORF L7095 encoding the putative cytotoxin. To observe more closely these compositional shifts in the different segments of pO157, we studied the variation in the third position of the codons of each gene. The third position is less constrained by selection than the first two, and base composition at this position is indicative of rates and patterns of mutation (73). Figure Figure 5. Third codon position composition. For each gene of pO157, the percentage of each base occurring in the third codon positions was calculated, and plotted against the coordinate on the pO157 sequence at the center of each gene. The composition of the etp and hly operons, and that of L7095 (red symbols) is different from that of adjacent genes. The values for katP and espP are also shown in red for comparison. The positions of the IS elements are shown by shaded bars. The complete sequence of this plasmid has revealed a number of potential virulence genes, consistent with a role for the plasmid in the pathogenic mechanism of O157:H7. From this point of view, the most significant discovery in pO157 is the putative new cytotoxin. This molecule potentially represents a new type of toxin since its third domain has no clear resemblance to any of the known motifs that mediate binding to the target cell. The similarity with the LCTs suggests a common effector mechanism leading to disorganization of the target cell's cytoskeleton. EHEC infection induces morphological changes in intestinal cells, resulting in the characteristic pedestal structure to which the bacteria attach. This is accompanied by changes in actin distribution and leads to new actin structures forming beneath the pedestal. Several genes involved in this process have been identified (reviewed in 8), but the biochemical details are not yet known. Thus, experimental investigation of the L7095 protein may add crucial understanding of EHEC disease. The emerging picture from partial sequences indicates that Gram-negative plasmid genomes are dynamic, with frequent transfer and recombination events among and between strains and even species. The complete plasmid sequence reported here is consistent with this, and with the notion that extrachromosomal elements such as plasmids and bacteriophages play a significant role in bringing together the virulence factors that make up the disease-potential of the organism. The sequence reveals a backbone of typical F-like replication and maintenance features like those previously reported for plasmids bearing virulence factors and drug resistances (57,58). Interspersed among the plasmid functions are genes and gene groups that have confirmed (e.g. hlyABCD) or putative (e.g. L7095) virulence potential, together forming a mosaic of elements of widely varying size assembled in the course of evolution (26), reflecting the situation in the O157:H7 chromosome (74). Although the transfer functions that would have mobilized these elements have been destroyed by insertion of the putative cytotoxin gene, the IS elements may be equally effective in mediating genetic mobility. We are beginning to discern the dynamic exchange of virulence determinants resulting in a reassortment of different pathogenic mechanisms. These observations suggest that the sum of all the pathogenic genes shared among related enteric bacteria form a pool or 'pathosphere', and that plasmids and genomes contain genes from this pool assembled by mechanisms that are, in evolutionary terms, relatively fast. This is paper 3508 from the Laboratory of Genetics. The work was supported by a research grant from the Ronald McDonald House Charities. N.T.P. is supported by NSF-Sloan Foundation Postdoctoral Fellowship BIR-9626042. We thank D. Rose, G. Mayhew and the technical staff of the Wisconsin Genome Project for help with sequencing, and Dr R. A. Welch for useful discussions and critical reading of the manuscript.
RESULTS AND DISCUSSION
Organization and physical properties
New putative virulence gene
Previously sequenced virulence genes
General secretory pathway
Other putative proteins
Replication regions and plasmid maintenance
Transfer region
Insertion sequence elements
IS element
Similarity
% (nt)aGenBank
Location
Coding regionsb
ORF length
(aa)Inverted repeats
IS629a
95.7
X51586
53269..54578
(53311..54201)
(54201..54524)296
10827 bp
IS629b
80.4
X51586
9831..11103
10174..11061
295
one only 27 bp
IS911
90.7
X17613
37521..38772
37557..37898
37943..38764113
27336 bp
ISx (IS3)
51.0
X02311
77032..77764
(77322..77681)
119
none
ISx (IS21)
71.2
X14793
77768..78257
77863..78273
136
none
ISy (IS3)
91.2
X02311
88137..88348
88143..88415
90
none
ISy (IS629)
69.0
X51586
88476..88899
(88342..88845)
167
one only 27 bp
ISz (IS91)
59.5
X17114
5661..7215
(5755..5976)
(6547..7056) 73
169one only 8 bp
ISz (IS600)
89.1
X05952
5986..6667
(6029..6763)
244
one only 27 bp
isoIS1N
77.7
J01737
15462..15926
(15609..15881)
90
none
Tn801
Phylogeny
Base distribution
ACKNOWLEDGEMENTS
REFERENCES
This article has been cited by other articles:
This page is run by Oxford University Press, Great Clarendon Street, Oxford OX2 6DP, as part of the OUP Journals
Comments and feedback: www-admin{at}oup.co.uk
Last modification: 29 Aug 1998
Copyright©Oxford University Press, 1998.
CiteULike 
Connotea 
Del.icio.us What's this?
T. J. Johnson and L. K. Nolan
Pathogenomics of the Virulence Plasmids of Escherichia coli
Microbiol. Mol. Biol. Rev.,
December 1, 2009;
73(4):
750 - 774.
[Abstract]
[Full Text]
[PDF]
T. Slanec, A. Fruth, K. Creuzburg, and H. Schmidt
Molecular Analysis of Virulence Profiles and Shiga Toxin Genes in Food-Borne Shiga Toxin-Producing Escherichia coli
Appl. Envir. Microbiol.,
October 1, 2009;
75(19):
6187 - 6197.
[Abstract]
[Full Text]
[PDF]
F. Zhuang, M. Karberg, J. Perutka, and A. M. Lambowitz
EcI5, a group IIB intron with high retrohoming frequency: DNA target site recognition and use in gene targeting
RNA,
March 1, 2009;
15(3):
432 - 449.
[Abstract]
[Full Text]
[PDF]
M. Bielaszewska, R. Prager, L. Vandivinit, A. Musken, A. Mellmann, N. J. Holt, P. I. Tarr, H. Karch, and W. Zhang
Detection and Characterization of the Fimbrial sfp Cluster in Enterohemorrhagic Escherichia coli O165:H25/NM Isolates from Humans and Cattle
Appl. Envir. Microbiol.,
January 1, 2009;
75(1):
64 - 71.
[Abstract]
[Full Text]
[PDF]
H. Suzuki, M. Sota, C. J. Brown, and E. M. Top
Using Mahalanobis distance to compare genomic signatures between bacterial plasmids and chromosomes
Nucleic Acids Res.,
December 1, 2008;
36(22):
e147 - e147.
[Abstract]
[Full Text]
[PDF]
T. Saitoh, S. Iyoda, S. Yamamoto, Y. Lu, K. Shimuta, M. Ohnishi, J. Terajima, and H. Watanabe
Transcription of the ehx Enterohemolysin Gene Is Positively Regulated by GrlA, a Global Regulator Encoded within the Locus of Enterocyte Effacement in Enterohemorrhagic Escherichia coli
J. Bacteriol.,
July 15, 2008;
190(14):
4822 - 4830.
[Abstract]
[Full Text]
[PDF]
A. Musken, M. Bielaszewska, L. Greune, C. H. Schweppe, J. Muthing, H. Schmidt, M. A. Schmidt, H. Karch, and W. Zhang
Anaerobic Conditions Promote Expression of Sfp Fimbriae and Adherence of Sorbitol-Fermenting Enterohemorrhagic Escherichia coli O157:NM to Human Intestinal Epithelial Cells
Appl. Envir. Microbiol.,
February 15, 2008;
74(4):
1087 - 1093.
[Abstract]
[Full Text]
[PDF]
A. Carattoli, A. Garcia-Fernandez, P. Varesi, D. Fortini, S. Gerardi, A. Penni, C. Mancini, and A. Giordano
Molecular Epidemiology of Escherichia coli Producing Extended-Spectrum -Lactamases Isolated in Rome, Italy
J. Clin. Microbiol.,
January 1, 2008;
46(1):
103 - 108.
[Abstract]
[Full Text]
[PDF]
A. G. Torres, G. N. Lopez-Sanchez, L. Milflores-Flores, S. D. Patel, M. Rojas-Lopez, C. F. Martinez de la Pena, M. M. P. Arenas-Hernandez, and Y. Martinez-Laguna
Ler and H-NS, Regulators Controlling Expression of the Long Polar Fimbriae of Escherichia coli O157:H7
J. Bacteriol.,
August 15, 2007;
189(16):
5916 - 5928.
[Abstract]
[Full Text]
[PDF]
T. Naas, D. Aubert, A. Ozcan, and P. Nordmann
Chromosome-Encoded Narrow-Spectrum Ambler Class A {beta}-Lactamase GIL-1 from Citrobacter gillenii
Antimicrob. Agents Chemother.,
April 1, 2007;
51(4):
1365 - 1372.
[Abstract]
[Full Text]
[PDF]
J. Y. Lim, H. Sheng, K. S. Seo, Y. H. Park, and C. J. Hovde
Characterization of an Escherichia coli O157:H7 Plasmid O157 Deletion Mutant and Its Survival and Persistence in Cattle
Appl. Envir. Microbiol.,
April 1, 2007;
73(7):
2037 - 2047.
[Abstract]
[Full Text]
[PDF]
M. Steele, K. Ziebell, Y. Zhang, A. Benson, P. Konczy, R. Johnson, and V. Gannon
Identification of Escherichia coli O157:H7 Genomic Regions Conserved in Strains with a Genotype Associated with Human Infection
Appl. Envir. Microbiol.,
January 1, 2007;
73(1):
22 - 31.
[Abstract]
[Full Text]
[PDF]
C. Brinkley, V. Burland, R. Keller, D. J. Rose, A. T. Boutin, S. A. Klink, F. R. Blattner, and J. B. Kaper
Nucleotide Sequence Analysis of the Enteropathogenic Escherichia coli Adherence Factor Plasmid pMAR7
Infect. Immun.,
September 1, 2006;
74(9):
5408 - 5413.
[Abstract]
[Full Text]
[PDF]
C.-C. Chen and S.-T. Hu
Two Frameshift Products Involved in the Transposition of Bacterial Insertion Sequence IS629
J. Biol. Chem.,
August 4, 2006;
281(31):
21617 - 21628.
[Abstract]
[Full Text]
[PDF]
R. A. Rashid, T. A. Tabata, M. J. Oatley, T. E. Besser, P. I. Tarr, and S. L. Moseley
Expression of Putative Virulence Factors of Escherichia coli O157:H7 Differs in Bovine and Human Infections
Infect. Immun.,
July 1, 2006;
74(7):
4142 - 4148.
[Abstract]
[Full Text]
[PDF]
T. E. Grys, L. L. Walters, and R. A. Welch
Characterization of the StcE Protease Activity of Escherichia coli O157:H7
J. Bacteriol.,
July 1, 2006;
188(13):
4646 - 4653.
[Abstract]
[Full Text]
[PDF]
M. A. Toleman, P. M. Bennett, and T. R. Walsh
ISCR Elements: Novel Gene-Capturing Systems of the 21st Century?
Microbiol. Mol. Biol. Rev.,
June 1, 2006;
70(2):
296 - 316.
[Abstract]
[Full Text]
[PDF]
M. Adamczyk, P. Dolowy, M. Jonczyk, C. M. Thomas, and G. Jagura-Burdzy
The kfrA gene is the first in a tricistronic operon required for survival of IncP-1 plasmid R751
Microbiology,
June 1, 2006;
152(6):
1621 - 1637.
[Abstract]
[Full Text]
[PDF]
W. Zhang, W. Qi, T. J. Albert, A. S. Motiwala, D. Alland, E. K. Hyytia-Trees, E. M. Ribot, P. I. Fields, T. S. Whittam, and B. Swaminathan
Probing genomic diversity and evolution of Escherichia coli O157 by single nucleotide polymorphisms
Genome Res.,
June 1, 2006;
16(6):
757 - 767.
[Abstract]
[Full Text]
[PDF]
R. Tozzoli, A. Caprioli, and S. Morabito
Detection of toxB, a Plasmid Virulence Gene of Escherichia coli O157, in Enterohemorrhagic and Enteropathogenic E. coli
J. Clin. Microbiol.,
August 1, 2005;
43(8):
4052 - 4056.
[Abstract]
[Full Text]
[PDF]
E. Frirdich and C. Whitfield
Review: Lipopolysaccharide inner core oligosaccharide structure and outer membrane stability in human pathogens belonging to the Enterobacteriaceae
Innate Immunity,
June 1, 2005;
11(3):
133 - 144.
[Abstract]
[PDF]
M. John, I. T. Kudva, R. W. Griffin, A. W. Dodson, B. McManus, B. Krastins, D. Sarracino, A. Progulske-Fox, J. D. Hillman, M. Handfield, et al.
Use of In Vivo-Induced Antigen Technology for Identification of Escherichia coli O157:H7 Proteins Expressed during Human Infection
Infect. Immun.,
May 1, 2005;
73(5):
2665 - 2679.
[Abstract]
[Full Text]
[PDF]
J. W. Yoon, J. Y. Lim, Y. H. Park, and C. J. Hovde
Involvement of the Escherichia coli O157:H7(pO157) ecf Operon and Lipid A Myristoyl Transferase Activity in Bacterial Survival in the Bovine Gastrointestinal Tract and Bacterial Persistence in Farm Water Troughs
Infect. Immun.,
April 1, 2005;
73(4):
2367 - 2378.
[Abstract]
[Full Text]
[PDF]
R. Szczepanowski, S. Braun, V. Riedel, S. Schneiker, I. Krahn, A. Puhler, and A. Schluter
The 120 592 bp IncF plasmid pRSB107 isolated from a sewage-treatment plant encodes nine different antibiotic-resistance determinants, two iron-acquisition systems and other putative virulence-associated functions
Microbiology,
April 1, 2005;
151(4):
1095 - 1111.
[Abstract]
[Full Text]
[PDF]
T. E. Grys, M. B. Siegel, W. W. Lathem, and R. A. Welch
The StcE Protease Contributes to Intimate Adherence of Enterohemorrhagic Escherichia coli O157:H7 to Host Cells
Infect. Immun.,
March 1, 2005;
73(3):
1295 - 1303.
[Abstract]
[Full Text]
[PDF]
M. P. Stevens, A. J. Roe, I. Vlisidou, P. M. van Diemen, R. M. La Ragione, A. Best, M. J. Woodward, D. L. Gally, and T. S. Wallis
Mutation of toxB and a Truncated Version of the efa-1 Gene in Escherichia coli O157:H7 Influences the Expression and Secretion of Locus of Enterocyte Effacement-Encoded Proteins but not Intestinal Colonization in Calves or Sheep
Infect. Immun.,
September 1, 2004;
72(9):
5402 - 5411.
[Abstract]
[Full Text]
[PDF]
N. A. Kaniuk, E. Vinogradov, J. Li, M. A. Monteiro, and C. Whitfield
Chromosomal and Plasmid-encoded Enzymes Are Required for Assembly of the R3-type Core Oligosaccharide in the Lipopolysaccharide of Escherichia coli O157:H7
J. Biol. Chem.,
July 23, 2004;
279(30):
31237 - 31250.
[Abstract]
[Full Text]
[PDF]
S.-H. Kim, W. Jia, R. E. Bishop, and C. Gyles
An msbB Homologue Carried in Plasmid pO157 Encodes an Acyltransferase Involved in Lipid A Biosynthesis in Escherichia coli O157:H7
Infect. Immun.,
February 1, 2004;
72(2):
1174 - 1180.
[Abstract]
[Full Text]
[PDF]
R. Mills, M. Rozanov, A. Lomsadze, T. Tatusova, and M. Borodovsky
Improving gene annotation of complete viral genomes
Nucleic Acids Res.,
December 1, 2003;
31(23):
7041 - 7055.
[Abstract]
[Full Text]
[PDF]
D. L. Leyton, J. Sloan, R. E. Hill, S. Doughty, and E. L. Hartland
Transfer Region of pO113 from Enterohemorrhagic Escherichia coli: Similarity with R64 and Identification of a Novel Plasmid-Encoded Autotransporter, EpeA
Infect. Immun.,
November 1, 2003;
71(11):
6307 - 6319.
[Abstract]
[Full Text]
[PDF]
M. A. Karmali, M. Mascarenhas, S. Shen, K. Ziebell, S. Johnson, R. Reid-Smith, J. Isaac-Renton, C. Clark, K. Rahn, and J. B. Kaper
Association of Genomic O Island 122 of Escherichia coli EDL 933 with Verocytotoxin-Producing Escherichia coli Seropathotypes That Are Linked to Epidemic and/or Serious Disease
J. Clin. Microbiol.,
November 1, 2003;
41(11):
4930 - 4940.
[Abstract]
[Full Text]
[PDF]
E. M. Nielsen and M. T. Andersen
Detection and Characterization of Verocytotoxin-Producing Escherichia coli by Automated 5' Nuclease PCR Assay
J. Clin. Microbiol.,
July 1, 2003;
41(7):
2884 - 2893.
[Abstract]
[Full Text]
[PDF]
S. Bekal, R. Brousseau, L. Masson, G. Prefontaine, J. Fairbrother, and J. Harel
Rapid Identification of Escherichia coli Pathotypes by Virulence Gene Detection with DNA Microarrays
J. Clin. Microbiol.,
May 1, 2003;
41(5):
2113 - 2125.
[Abstract]
[Full Text]
[PDF]
T. Ide, S. Michgehl, S. Knappstein, G. Heusipp, and M. A. Schmidt
Differential Modulation by Ca2+ of Type III Secretion of Diffusely Adhering Enteropathogenic Escherichia coli
Infect. Immun.,
April 1, 2003;
71(4):
1725 - 1732.
[Abstract]
[Full Text]
[PDF]
M. Ohnishi, J. Terajima, K. Kurokawa, K. Nakayama, T. Murata, K. Tamura, Y. Ogura, H. Watanabe, and T. Hayashi
Genomic diversity of enterohemorrhagic Escherichia coli O157 revealed by whole genome PCR scanning
PNAS,
December 24, 2002;
99(26):
17043 - 17048.
[Abstract]
[Full Text]
[PDF]
S. Doughty, J. Sloan, V. Bennett-Wood, M. Robertson, R. M. Robins-Browne, and E. L. Hartland
Identification of a Novel Fimbrial Gene Cluster Related to Long Polar Fimbriae in Locus of Enterocyte Effacement-Negative Strains of Enterohemorrhagic Escherichia coli
Infect. Immun.,
December 1, 2002;
70(12):
6761 - 6769.
[Abstract]
[Full Text]
[PDF]
A. L. COOKSON, C. M. HAYES, G. R. PEARSON, J. M. ROE, A. D. WALES, and M. J. WOODWARD
Isolation from a sheep of an attaching and effacing Escherichia coli O115:H- with a novel combination of virulence factors
J. Med. Microbiol.,
December 1, 2002;
51(12):
1041 - 1049.
[Abstract]
[Full Text]
[PDF]
V. Dubois, C. Arpin, P. Noury, and C. Quentin
Clinical Strain of Pseudomonas aeruginosa Carrying a blaTEM-21 Gene Located on a Chromosomal Interrupted TnA Type Transposon
Antimicrob. Agents Chemother.,
November 1, 2002;
46(11):
3624 - 3626.
[Abstract]
[Full Text]
[PDF]
J. L. Martinez and F. Baquero
Interactions among Strategies Associated with Bacterial Infection: Pathogenicity, Epidemicity, and Antibiotic Resistance
Clin. Microbiol. Rev.,
October 1, 2002;
15(4):
647 - 679.
[Abstract]
[Full Text]
[PDF]
M. P. Stevens, P. M. van Diemen, G. Frankel, A. D. Phillips, and T. S. Wallis
Efa1 Influences Colonization of the Bovine Intestine by Shiga Toxin-Producing Escherichia coli Serotypes O5 and O111
Infect. Immun.,
September 1, 2002;
70(9):
5158 - 5166.
[Abstract]
[Full Text]
[PDF]
A. D. WALES, F. A. CLIFTON-HADLEY, A. L. COOKSON, M. P. DIBB-FULLER, R. M. LARAGIONE, G. R. PEARSON, and M. J. WOODWARD
Production of attaching-effacing lesions in ligated large intestine loops of 6-month-old sheep by Escherichia coli O157:H7
J. Med. Microbiol.,
September 1, 2002;
51(9):
755 - 763.
[Abstract]
[Full Text]
[PDF]
P. Srimanote, A. W. Paton, and J. C. Paton
Characterization of a Novel Type IV Pilus Locus Encoded on the Large Plasmid of Locus of Enterocyte Effacement-Negative Shiga-Toxigenic Escherichia coli Strains That Are Virulent for Humans
Infect. Immun.,
June 1, 2002;
70(6):
3094 - 3100.
[Abstract]
[Full Text]
[PDF]
H. d'Hauteville, S. Khan, D. J. Maskell, A. Kussak, A. Weintraub, J. Mathison, R. J. Ulevitch, N. Wuscher, C. Parsot, and P. J. Sansonetti
Two msbB Genes Encoding Maximal Acylation of Lipid A Are Required for Invasive Shigella flexneri to Mediate Inflammatory Rupture and Destruction of the Intestinal Epithelium
J. Immunol.,
May 15, 2002;
168(10):
5240 - 5251.
[Abstract]
[Full Text]
[PDF]
N. Pradel, S. Leroy-Setrin, B. Joly, and V. Livrelli
Genomic Subtraction To Identify and Characterize Sequences of Shiga Toxin-Producing Escherichia coli O91:H21
Appl. Envir. Microbiol.,
May 1, 2002;
68(5):
2316 - 2325.
[Abstract]
[Full Text]
[PDF]
I. T. Kudva, P. S. Evans, N. T. Perna, T. J. Barrett, F. M. Ausubel, F. R. Blattner, and S. B. Calderwood
Strains of Escherichia coli O157:H7 Differ Primarily by Insertions or Deletions, Not Single-Nucleotide Polymorphisms
J. Bacteriol.,
April 1, 2002;
184(7):
1873 - 1879.
[Abstract]
[Full Text]
[PDF]
A. W. Paton and J. C. Paton
Reactivity of Convalescent-Phase Hemolytic-Uremic Syndrome Patient Sera with the Megaplasmid-Encoded TagA Protein of Shiga Toxigenic Escherichia coli O157
J. Clin. Microbiol.,
April 1, 2002;
40(4):
1395 - 1399.
[Abstract]
[Full Text]
[PDF]
I. Tatsuno, M. Horie, H. Abe, T. Miki, K. Makino, H. Shinagawa, H. Taguchi, S. Kamiya, T. Hayashi, and C. Sasakawa
toxB Gene on pO157 of Enterohemorrhagic Escherichiacoli O157:H7 Is Required for Full Epithelial Cell Adherence Phenotype
Infect. Immun.,
November 1, 2001;
69(11):
6660 - 6669.
[Abstract]
[Full Text]
[PDF]
A. W. Paton, P. Srimanote, M. C. Woodrow, and J. C. Paton
Characterization of Saa, a Novel Autoagglutinating Adhesin Produced by Locus of Enterocyte Effacement-Negative Shiga-Toxigenic Escherichia coli Strains That Are Virulent for Humans
Infect. Immun.,
November 1, 2001;
69(11):
6999 - 7009.
[Abstract]
[Full Text]
[PDF]
S. N. Luck, S. A. Turner, K. Rajakumar, H. Sakellaris, and B. Adler
Ferric Dicitrate Transport System (Fec) of Shigella flexneri 2a YSH6000 Is Encoded on a Novel Pathogenicity Island Carrying Multiple Antibiotic Resistance Genes
Infect. Immun.,
October 1, 2001;
69(10):
6012 - 6021.
[Abstract]
[Full Text]
[PDF]
W. Deng, Y. Li, B. A. Vallance, and B. B. Finlay
Locus of Enterocyte Effacement from Citrobacter rodentium: Sequence Analysis and Evidence for Horizontal Transfer among Attaching and Effacing Pathogens
Infect. Immun.,
October 1, 2001;
69(10):
6323 - 6335.
[Abstract]
[Full Text]
[PDF]
I. N. Okeke, J. A. Borneman, S. Shin, J. L. Mellies, L. E. Quinn, and J. B. Kaper
Comparative Sequence Analysis of the Plasmid-Encoded Regulator of Enteropathogenic Escherichia coli Strains
Infect. Immun.,
September 1, 2001;
69(9):
5553 - 5564.
[Abstract]
[Full Text]
[PDF]
A. McNally, A. J. Roe, S. Simpson, F. M. Thomson-Carter, D. E. E. Hoey, C. Currie, T. Chakraborty, D. G. E. Smith, and D. L. Gally
Differences in Levels of Secreted Locus of Enterocyte Effacement Proteins between Human Disease-Associated and Bovine Escherichia coli O157
Infect. Immun.,
August 1, 2001;
69(8):
5107 - 5114.
[Abstract]
[Full Text]
[PDF]
E J Elliott, R M Robins-Browne, E V O'Loughlin, V Bennett-Wood, J Bourke, P Henning, G G Hogg, J Knight, H Powell, D Redmond, et al.
Nationwide study of haemolytic uraemic syndrome: clinical, microbiological, and epidemiological features
Arch. Dis. Child.,
August 1, 2001;
85(2):
125 - 131.
[Abstract]
[Full Text]
[PDF]
W. Brunder, A. S. Khan, J. Hacker, and H. Karch
Novel Type of Fimbriae Encoded by the Large Plasmid of Sorbitol-Fermenting Enterohemorrhagic Escherichia coli O157:H{-}
Infect. Immun.,
July 1, 2001;
69(7):
4447 - 4457.
[Abstract]
[Full Text]
[PDF]
N. Pradel, K. Boukhors, Y. Bertin, C. Forestier, C. Martin, and V. Livrelli
Heterogeneity of Shiga Toxin-Producing Escherichia coli Strains Isolated from Hemolytic-Uremic Syndrome Patients, Cattle, and Food Samples in Central France
Appl. Envir. Microbiol.,
June 1, 2001;
67(6):
2460 - 2468.
[Abstract]
[Full Text]
M. Sandkvist
Type II Secretion and Pathogenesis
Infect. Immun.,
June 1, 2001;
69(6):
3523 - 3535.
[Full Text]
[PDF]
M. M. Venkatesan, M. B. Goldberg, D. J. Rose, E. J. Grotbeck, V. Burland, and F. R. Blattner
Complete DNA Sequence and Analysis of the Large Virulence Plasmid of Shigella flexneri
Infect. Immun.,
May 1, 2001;
69(5):
3271 - 3285.
[Abstract]
[Full Text]
[PDF]
M. B. Prentice, K. D. James, J. Parkhill, S. G. Baker, K. Stevens, M. N. Simmonds, K. L. Mungall, C. Churcher, P. C. F. Oyston, R. W. Titball, et al.
Yersinia pestis pFra Shows Biovar-Specific Differences and Recent Common Ancestry with a Salmonella enterica Serovar Typhi Plasmid
J. Bacteriol.,
April 15, 2001;
183(8):
2586 - 2594.
[Abstract]
[Full Text]
C. Zhu, T. S. Agin, S. J. Elliott, L. A. Johnson, T. E. Thate, J. B. Kaper, and E. C. Boedeker
Complete Nucleotide Sequence and Analysis of the Locus of Enterocyte Effacement from Rabbit Diarrheagenic Escherichia coli RDEC-1
Infect. Immun.,
April 1, 2001;
69(4):
2107 - 2115.
[Abstract]
[Full Text]
[PDF]
T. Haneda, N. Okada, N. Nakazawa, T. Kawakami, and H. Danbara
Complete DNA Sequence and Comparative Analysis of the 50-Kilobase Virulence Plasmid of Salmonella enterica Serovar Choleraesuis
Infect. Immun.,
April 1, 2001;
69(4):
2612 - 2620.
[Abstract]
[Full Text]
[PDF]
J. L. Mellies, F. Navarro-Garcia, I. Okeke, J. Frederickson, J. P. Nataro, and J. B. Kaper
espC Pathogenicity Island of Enteropathogenic Escherichia coli Encodes an Enterotoxin
Infect. Immun.,
January 1, 2001;
69(1):
315 - 324.
[Abstract]
[Full Text]
[PDF]
S. J. Elliott, V. Sperandio, J. A. Giron, S. Shin, J. L. Mellies, L. Wainwright, S. W. Hutcheson, T. K. McDaniel, and J. B. Kaper
The Locus of Enterocyte Effacement (LEE)-Encoded Regulator Controls Expression of Both LEE- and Non-LEE-Encoded Virulence Factors in Enteropathogenic and Enterohemorrhagic Escherichia coli
Infect. Immun.,
November 1, 2000;
68(11):
6115 - 6126.
[Abstract]
[Full Text]
[PDF]
P. M. Bavoil, R.-c. Hsia, and D. M. Ojcius
Closing in on Chlamydia and its intracellular bag of tricks
Microbiology,
November 1, 2000;
146(11):
2723 - 2731.
[Full Text]
S. Yaron, G. L. Kolling, L. Simon, and K. R. Matthews
Vesicle-Mediated Transfer of Virulence Genes from Escherichia coli O157:H7 to Other Enteric Bacteria
Appl. Envir. Microbiol.,
October 1, 2000;
66(10):
4414 - 4420.
[Abstract]
[Full Text]
M. Picardeau, J. R. Lobry, and B. J. Hinnebusch
Analyzing DNA Strand Compositional Asymmetry to Identify Candidate Replication Origins of Borrelia burgdorferi Linear and Circular Plasmids
Genome Res.,
October 1, 2000;
10(10):
1594 - 1604.
[Abstract]
[Full Text]
R. H. Ffrench-Constant, N. Waterfield, V. Burland, N. T. Perna, P. J. Daborn, D. Bowen, and F. R. Blattner
A Genomic Sample Sequence of the Entomopathogenic Bacterium Photorhabdus luminescens W14: Potential Implications for Virulence
Appl. Envir. Microbiol.,
August 1, 2000;
66(8):
3310 - 3329.
[Abstract]
[Full Text]
C. K. Sherburne, T. D. Lawley, M. W. Gilmour, F. R. Blattner, V. Burland, E. Grotbeck, D. J. Rose, and D. E. Taylor
The complete DNA sequence and analysis of R27, a large IncHI plasmid from Salmonella typhi that is temperature sensitive for transfer
Nucleic Acids Res.,
May 15, 2000;
28(10):
2177 - 2186.
[Abstract]
[Full Text]
[PDF]
J.-M. A. Klapproth, I. C. A. Scaletsky, B. P. McNamara, L.-C. Lai, C. Malstrom, S. P. James, and M. S. Donnenberg
A Large Toxin from Pathogenic Escherichia coli Strains That Inhibits Lymphocyte Activation
Infect. Immun.,
April 1, 2000;
68(4):
2148 - 2155.
[Abstract]
[Full Text]
[PDF]
T. D. Read, R. C. Brunham, C. Shen, S. R. Gill, J. F. Heidelberg, O. White, E. K. Hickey, J. Peterson, T. Utterback, K. Berry, et al.
Genome sequences of Chlamydia trachomatis MoPn and Chlamydia pneumoniae AR39
Nucleic Acids Res.,
March 15, 2000;
28(6):
1397 - 1406.
[Abstract]
[Full Text]
[PDF]
M. Kusumoto, Y. Nishiya, and Y. Kawamura
Reactivation of Insertionally Inactivated Shiga Toxin 2 Genes of Escherichia coli O157:H7 Caused by Nonreplicative Transposition of the Insertion Sequence
Appl. Envir. Microbiol.,
March 1, 2000;
66(3):
1133 - 1138.
[Abstract]
[Full Text]
T. Tobe, T. Hayashi, C.-G. Han, G. K. Schoolnik, E. Ohtsubo, and C. Sasakawa
Complete DNA Sequence and Structural Analysis of the Enteropathogenic Escherichia coli Adherence Factor Plasmid
Infect. Immun.,
October 1, 1999;
67(10):
5455 - 5462.
[Abstract]
[Full Text]
[PDF]
Y. Wang, S.-H. Huang, C. A. Wass, M. F. Stins, and K. S. Kim
The Gene Locus yijP Contributes to Escherichia coli K1 Invasion of Brain Microvascular Endothelial Cells
Infect. Immun.,
September 1, 1999;
67(9):
4751 - 4756.
[Abstract]
[Full Text]
[PDF]
G. Plunkett III, D. J. Rose, T. J. Durfee, and F. R. Blattner
Sequence of Shiga Toxin 2 Phage 933W from Escherichia coli O157:H7: Shiga Toxin as a Phage Late-Gene Product
J. Bacteriol.,
March 15, 1999;
181(6):
1767 - 1778.
[Abstract]
[Full Text]
This Article 
Abstract
Alert me when this article is cited
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in ISI Web of Science
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Search for citing articles in:
ISI Web of Science (156)
Request Permissions
Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Articles by Burland, V.
Articles by Blattner, F. R.
Search for Related Content
PubMed
PubMed Citation
Articles by Burland, V.
Articles by Blattner, F. R.
Social Bookmarking
What's this?