Publications (64)490.36 Total impact
-
Article: Quantitative Polymerase Chain Reaction for Detection of Shigella Improves Ascertainment of Shigella Burden in Children with Moderate to Severe Diarrhea in Low Income Countries.
[show abstract] [hide abstract]
ABSTRACT: Estimates of Shigella prevalence are limited by suboptimal sensitivity of current methods. We used a quantitative (Q)PCR assay to detect Shigella in stools of 3,533 children aged less than 59 -months from The Gambia, Mali, Kenya and Bangladesh, with or without moderate to severe diarrhea (MSD). We compared the results of conventional culture to those of QPCR for the Shigella ipaH gene. Using MSD as the reference standard, we determined the optimal cut point to be 2.9x10E4 ipaH gene copies per 100 ng of stool DNA for Set 1 (N=877). One-hundred and fifty-eight (18%) samples specimens yielded greater than 2.9x10E4 ipaH gene copies. Ninety (10%) specimens were positive by traditional culture for Shigella. Individuals with a value of ≥2.9x10E4 have 5.6 times higher odds of having diarrhea compared to those with values <2.9x10E4 (95%CI 3.7-8.5; p<0.0001). Nearly identical results were found using an independent set of samples. QPCR detected 155 additional MSD cases with high copy numbers of ipaH, a 90% increase from the 172 cases detected by culture within both samples. Among a subset (N=2,874) comprising MSD cases, and age-, gender- and location-matched controls, the fraction of MSD cases attributable to Shigella infection increased from 9.6% (N=129) for culture to 17.6% (N=262) for QPCR employing our cut-point. We suggest that QPCR with a cut-point of approximately 1.4×10E4 become the new reference standard for the detection and diagnosis of Shigellosis in children in low-income countries. Acceptance of a new standard would substantially increase the fraction of MSD attributable to Shigella.Journal of clinical microbiology 03/2013; · 4.16 Impact Factor -
Article: Transcriptional Modulation of Enterotoxigenic Escherichia coli Virulence Genes in Response to Epithelial Cell Interactions.
[show abstract] [hide abstract]
ABSTRACT: Enterotoxigenic Escherichia coli are a leading cause of morbidity and mortality due to diarrheal illness in developing countries. There is currently no effective vaccine against these important pathogens. Because genes modulated by pathogen-host interactions potentially encode putative vaccine targets, we investigated changes in gene expression and surface morphology of ETEC upon interaction with intestinal epithelial cells in vitro. Pan-genome microarrays, quantitative reverse transcriptase PCR (qRT-PCR), and transcriptional reporter fusions of selected promoters were used to study changes in ETEC transcriptomes. Flow cytometry, immunofluorescence microscopy, and scanning electron microscopy were used to investigate alterations in surface antigen expression and morphology following pathogen-host interactions. Following host cell contact, genes for motility, adhesion, toxin production, immunodominant peptides, and key regulatory molecules including CRP and c-di-GMP were substantially modulated. These changes were accompanied by visible changes in both ETEC architecture and the expression of surface antigens including a novel highly conserved adhesin molecule, EaeH. The studies reported here suggest that pathogen-host interactions are finely orchestrated by ETEC, and are characterized by coordinated responses involving the sequential deployment of multiple virulence molecules. Elucidation of the molecular details of these interactions could highlight novel strategies for development of vaccines for these important pathogens.Infection and immunity 10/2012; · 4.21 Impact Factor -
Article: Hybrid error correction and de novo assembly of single-molecule sequencing reads.
[show abstract] [hide abstract]
ABSTRACT: Single-molecule sequencing instruments can generate multikilobase sequences with the potential to greatly improve genome and transcriptome assembly. However, the error rates of single-molecule reads are high, which has limited their use thus far to resequencing bacteria. To address this limitation, we introduce a correction algorithm and assembly strategy that uses short, high-fidelity sequences to correct the error in single-molecule sequences. We demonstrate the utility of this approach on reads generated by a PacBio RS instrument from phage, prokaryotic and eukaryotic whole genomes, including the previously unsequenced genome of the parrot Melopsittacus undulatus, as well as for RNA-Seq reads of the corn (Zea mays) transcriptome. Our long-read correction achieves >99.9% base-call accuracy, leading to substantially better assemblies than current sequencing strategies: in the best example, the median contig size was quintupled relative to high-coverage, second-generation assemblies. Greater gains are predicted if read lengths continue to increase, including the prospect of single-contig bacterial chromosome assembly.Nature Biotechnology 07/2012; 30(7):693-700. · 29.50 Impact Factor -
Article: Genome sequence of Klebsiella oxytoca 11492-1, a nosocomial isolate possessing a FOX-5 AmpC β-lactamase.
[show abstract] [hide abstract]
ABSTRACT: Klebsiella oxytoca strain 11492-1 was isolated from a perianal swab culture from a patient at the University of Maryland Medical Center in 2005. The K. oxytoca 11492-1 draft genome contains multiple antibiotic resistance genes, including a FOX-5 AmpC β-lactamase encoded on a large IncA/C plasmid.Journal of bacteriology 06/2012; 194(11):3028-9. · 3.94 Impact Factor -
Article: Draft genome sequences of the diarrheagenic Escherichia coli collection.
[show abstract] [hide abstract]
ABSTRACT: We report the draft genome sequences of the collection referred to as the Escherichia coli DECA collection, which was assembled to contain representative isolates of the 15 most common diarrheagenic clones in humans (http://shigatox.net/new/). These genomes represent a valuable resource to the community of researchers who examine these enteric pathogens.Journal of bacteriology 06/2012; 194(11):3026-7. · 3.94 Impact Factor -
Article: Phylomark, a tool to identify conserved phylogenetic markers from whole-genome alignments.
[show abstract] [hide abstract]
ABSTRACT: The sequencing and analysis of multiple housekeeping genes has been routinely used to phylogenetically compare closely related bacterial isolates. Recent studies using whole-genome alignment (WGA) and phylogenetics from >100 Escherichia coli genomes has demonstrated that tree topologies from WGA and multilocus sequence typing (MLST) markers differ significantly. A nonrepresentative phylogeny can lead to incorrect conclusions regarding important evolutionary relationships. In this study, the Phylomark algorithm was developed to identify a minimal number of useful phylogenetic markers that recapitulate the WGA phylogeny. To test the algorithm, we used a set of diverse draft and complete E. coli genomes. The algorithm identified more than 100,000 potential markers of different fragment lengths (500 to 900 nucleotides). Three molecular markers were ultimately chosen to determine the phylogeny based on a low Robinson-Foulds (RF) distance compared to the WGA phylogeny. A phylogenetic analysis demonstrated that a more representative phylogeny was inferred for a concatenation of these markers compared to all other MLST schemes for E. coli. As a functional test of the algorithm, the three markers (genomic guided E. coli markers, or GIG-EM) were amplified and sequenced from a set of environmental E. coli strains (ECOR collection) and informatically extracted from a set of 78 diarrheagenic E. coli strains (DECA collection). In the instances of the 40-genome test set and the DECA collection, the GIG-EM system outperformed other E. coli MLST systems in terms of recapitulating the WGA phylogeny. This algorithm can be employed to determine the minimal marker set for any organism that has sufficient genome sequencing.Applied and environmental microbiology 05/2012; 78(14):4884-92. · 3.69 Impact Factor -
Article: Shigella flexneri effectors OspE1 and OspE2 mediate induced adherence to the colonic epithelium following bile salts exposure.
[show abstract] [hide abstract]
ABSTRACT: Shigella flexneri is a Gram-negative pathogen that invades the colonic epithelium. While invasion has been thoroughly investigated, it is unknown how Shigella first attaches to the epithelium. Previous literature suggests that Shigella utilizes adhesins that are induced by environmental signals, including bile salts, encountered in the small intestine prior to invasion. We hypothesized that bile would induce adherence factors to facilitate attachment to colonic epithelial cells. To test our hypothesis, S. flexneri strain 2457T was subcultured in media containing bile salts, and the ability of the bacteria to adhere to the apical surface of polarized T84 epithelial cells was measured. We observed a significant increase in adherence, which was absent in a virulence plasmid-cured strain and a type-III secretion system mutant. Microarray expression analysis indicated that the ospE1/ospE2 genes were induced in the presence of bile, and bile-induced adherence was lost in a ΔospE1/ΔospE2 mutant. Further studies demonstrated that the OspE1/OspE2 proteins were localized to the bacterial outer membrane following exposure to bile salts. The data presented are the first demonstration that the OspE1/OspE2 proteins promote initial adherence to the intestinal epithelium. The adhesins required for Shigella attachment to the colonic epithelium may serve as ideal targets for vaccine development.Molecular Microbiology 05/2012; 85(1):107-21. · 5.01 Impact Factor -
Article: Whole-genome sequences of Bacillus subtilis and close relatives.
[show abstract] [hide abstract]
ABSTRACT: We sequenced four strains of Bacillus subtilis and the type strains for two closely related species, Bacillus vallismortis and Bacillus mojavensis. We report the high-quality Sanger genome sequences of B. subtilis subspecies subtilis RO-NN-1 and AUSI98, B. subtilis subspecies spizizenii TU-B-10(T) and DV1-B-1, Bacillus mojavensis RO-H-1(T), and Bacillus vallismortis DV1-F-3(T).Journal of bacteriology 05/2012; 194(9):2378-9. · 3.94 Impact Factor -
Article: Genome sequences of four divergent multidrug-resistant Acinetobacter baumannii strains isolated from patients with sepsis or osteomyelitis.
[show abstract] [hide abstract]
ABSTRACT: Acinetobacter baumannii is a Gram-negative bacterium that causes nosocomial infections worldwide, with recent prevalence and higher frequency in wounded military personnel. Four A. baumannii strains from the Walter Reed Army Medical Center (WRAMC) isolated between 2008 and 2009 were sequenced, representing diverse, multidrug-resistant isolates from osteomyelitis or septic patients.Journal of bacteriology 03/2012; 194(6):1619-20. · 3.94 Impact Factor -
Article: Draft genome sequence of Vibrio fischeri SR5, a strain isolated from the light organ of the Mediterranean squid Sepiola robusta.
[show abstract] [hide abstract]
ABSTRACT: Here, we describe the draft genome sequence of Vibrio fischeri SR5, a squid symbiotic isolate from Sepiola robusta in the Mediterranean Sea. This 4.3-Mbp genome sequence represents the first V. fischeri genome from an S. robusta symbiont and the first from outside the Pacific Ocean.Journal of bacteriology 03/2012; 194(6):1639. · 3.94 Impact Factor -
Article: Analysis of global transcriptional profiles of enterotoxigenic Escherichia coli isolate E24377A.
[show abstract] [hide abstract]
ABSTRACT: Enterotoxigenic Escherichia coli (ETEC) is an important pathogenic variant (pathovar) of E. coli in developing countries from a human health perspective, causing significant morbidity and mortality. Previous studies have examined specific regulatory networks in ETEC, although little is known about the global effects of inter- and intrakingdom signaling on the expression of virulence and colonization factors in ETEC. In this study, an E. coli/Shigella pan-genome microarray, combined with quantitative reverse transcriptase PCR (qRT-PCR) and RNA sequencing (RNA-seq), was used to quantify the expression of ETEC virulence and colonization factors. Biologically relevant chemical signals were combined with ETEC isolate E24377A during growth in either Luria broth (LB) or Dulbecco's modified Eagle medium (DMEM), and transcription was examined during different phases of the growth cycle; chemical signals examined included glucose, bile salts, and preconditioned media from E. coli/Shigella isolates. The results demonstrate that the presence of bile salts, which are found in the intestine and thought to be bactericidal, upregulates the expression of many ETEC virulence factors, including heat-stable (estA) and heat-labile (eltA) enterotoxin genes. In contrast, the ETEC colonization factors CS1 and CS3 were downregulated in the presence of bile, consistent with findings in studies of other enteric pathogens. RNA-seq analysis demonstrated that one of the most differentially expressed genes in the presence of bile is a unique plasmid-encoded AraC-like transcriptional regulator (peaR); other previously unknown genetic elements were found as well. These results provide transcriptional targets and putative mechanisms that should help improve understanding of the global regulatory networks and virulence expression in this important human pathogen.Infection and immunity 01/2012; 80(3):1232-42. · 4.21 Impact Factor -
Article: Comparative Genomics and stx Phage Characterization of LEE-Negative Shiga Toxin-Producing Escherichia coli.
[show abstract] [hide abstract]
ABSTRACT: Infection by Escherichia coli and Shigella species are among the leading causes of death due to diarrheal disease in the world. Shiga toxin-producing E. coli (STEC) that do not encode the locus of enterocyte effacement (LEE-negative STEC) often possess Shiga toxin gene variants and have been isolated from humans and a variety of animal sources. In this study, we compare the genomes of nine LEE-negative STEC harboring various stx alleles with four complete reference LEE-positive STEC isolates. Compared to a representative collection of prototype E. coli and Shigella isolates representing each of the pathotypes, the whole genome phylogeny demonstrated that these isolates are diverse. Whole genome comparative analysis of the 13 genomes revealed that in addition to the absence of the LEE pathogenicity island, phage-encoded genes including non-LEE encoded effectors, were absent from all nine LEE-negative STEC genomes. Several plasmid-encoded virulence factors reportedly identified in LEE-negative STEC isolates were identified in only a subset of the nine LEE-negative isolates further confirming the diversity of this group. In combination with whole genome analysis, we characterized the lambdoid phages harboring the various stx alleles and determined their genomic insertion sites. Although the integrase gene sequence corresponded with genomic location, it was not correlated with stx variant, further highlighting the mosaic nature of these phages. The transcription of these phages in different genomic backgrounds was examined. Expression of the Shiga toxin genes, stx(1) and/or stx(2), as well as the Q genes, were examined with quantitative reverse transcriptase polymerase chain reaction assays. A wide range of basal and induced toxin induction was observed. Overall, this is a first significant foray into the genome space of this unexplored group of emerging and divergent pathogens.Frontiers in cellular and infection microbiology. 01/2012; 2:133. -
Article: Genomic characterization of enteroaggregative Escherichia coli from children in Mali.
[show abstract] [hide abstract]
ABSTRACT: Enteroaggregative Escherichia coli (EAEC) is a cause of epidemic and sporadic diarrhea, yet its role as an enteric pathogen is not fully understood. We characterized 121 EAEC strains isolated in 2008 as part of a case-control study of moderate to severe acute diarrhea among children 0-59 months of age in Bamako, Mali. We applied multiplex polymerase chain reaction and comparative genome hybridization to identify potential virulence factors among the EAEC strains, coupled with classification and regression tree modeling to reveal combinations of factors most strongly associated with illness. The gene encoding the autotransporter protease SepA, originally described in Shigella species, was most strongly associated with diarrhea among the EAEC strains tested (odds ratio, 5.6 [95% confidence interval, 1.92-16.17]; P = .0006). In addition, we identified 3 gene combinations correlated with diarrhea: (1) a clonal group positive for sepA and a putative hemolysin; (2) a group harboring the EAST-1 enterotoxin and the flagellar type H33 but no other previously identified EAEC virulence factor; and (3) a group carrying several of the typical EAEC virulence genes. Our data suggest that only a subset of EAEC strains are pathogenic in Mali and suggest that sepA may serve as a valuable marker for the most virulent isolates.The Journal of Infectious Diseases 12/2011; 205(3):431-44. · 6.41 Impact Factor -
Article: Hfq virulence regulation in enterohemorrhagic Escherichia coli O157:H7 strain 86-24.
[show abstract] [hide abstract]
ABSTRACT: Enterohemorrhagic Escherichia coli O157:H7 (EHEC) causes bloody diarrhea and hemolytic-uremic syndrome. EHEC encodes the sRNA chaperone Hfq, which is important in posttranscriptional regulation. In EHEC strain EDL933, Hfq acts as a negative regulator of the locus of enterocyte effacement (LEE), which encodes most of the proteins involved in type III secretion and attaching and effacing (AE) lesions. Here, we deleted hfq in the EHEC strain 86-24 and compared global transcription profiles of the hfq mutant and wild-type (WT) strains in exponential growth phase. Deletion of hfq affected transcription of genes common to nonpathogenic and pathogenic strains of E. coli as well as pathogen-specific genes. Downregulated genes in the hfq mutant included ler, the transcriptional activator of all the LEE genes, as well as genes encoded in the LEE2 to -5 operons. Decreased expression of the LEE genes in the hfq mutant occurred at middle, late, and stationary growth phases. We also confirmed decreased regulation of the LEE genes by examining the proteins secreted and AE lesion formation by the hfq mutant and WT strains. Deletion of hfq also caused decreased expression of the two-component system qseBC, which is involved in interkingdom signaling and virulence gene regulation in EHEC, as well as an increase in expression of stx(2AB), which encodes the deadly Shiga toxin. Altogether, these data indicate that Hfq plays a regulatory role in EHEC 86-24 that is different from what has been reported for EHEC strain EDL933 and that the role of Hfq in EHEC virulence regulation extends beyond the LEE.Journal of bacteriology 12/2011; 193(24):6843-51. · 3.94 Impact Factor -
Article: Origins of the E. coli strain causing an outbreak of hemolytic-uremic syndrome in Germany.
[show abstract] [hide abstract]
ABSTRACT: A large outbreak of diarrhea and the hemolytic-uremic syndrome caused by an unusual serotype of Shiga-toxin-producing Escherichia coli (O104:H4) began in Germany in May 2011. As of July 22, a large number of cases of diarrhea caused by Shiga-toxin-producing E. coli have been reported--3167 without the hemolytic-uremic syndrome (16 deaths) and 908 with the hemolytic-uremic syndrome (34 deaths)--indicating that this strain is notably more virulent than most of the Shiga-toxin-producing E. coli strains. Preliminary genetic characterization of the outbreak strain suggested that, unlike most of these strains, it should be classified within the enteroaggregative pathotype of E. coli. We used third-generation, single-molecule, real-time DNA sequencing to determine the complete genome sequence of the German outbreak strain, as well as the genome sequences of seven diarrhea-associated enteroaggregative E. coli serotype O104:H4 strains from Africa and four enteroaggregative E. coli reference strains belonging to other serotypes. Genomewide comparisons were performed with the use of these enteroaggregative E. coli genomes, as well as those of 40 previously sequenced E. coli isolates. The enteroaggregative E. coli O104:H4 strains are closely related and form a distinct clade among E. coli and enteroaggregative E. coli strains. However, the genome of the German outbreak strain can be distinguished from those of other O104:H4 strains because it contains a prophage encoding Shiga toxin 2 and a distinct set of additional virulence and antibiotic-resistance factors. Our findings suggest that horizontal genetic exchange allowed for the emergence of the highly virulent Shiga-toxin-producing enteroaggregative E. coli O104:H4 strain that caused the German outbreak. More broadly, these findings highlight the way in which the plasticity of bacterial genomes facilitates the emergence of new pathogens.New England Journal of Medicine 08/2011; 365(8):709-17. · 53.30 Impact Factor -
Article: Genomic comparison of multi-drug resistant invasive and colonizing Acinetobacter baumannii isolated from diverse human body sites reveals genomic plasticity.
[show abstract] [hide abstract]
ABSTRACT: Acinetobacter baumannii has recently emerged as a significant global pathogen, with a surprisingly rapid acquisition of antibiotic resistance and spread within hospitals and health care institutions. This study examines the genomic content of three A. baumannii strains isolated from distinct body sites. Isolates from blood, peri-anal, and wound sources were examined in an attempt to identify genetic features that could be correlated to each isolation source. Pulsed-field gel electrophoresis, multi-locus sequence typing and antibiotic resistance profiles demonstrated genotypic and phenotypic variation. Each isolate was sequenced to high-quality draft status, which allowed for comparative genomic analyses with existing A. baumannii genomes. A high resolution, whole genome alignment method detailed the phylogenetic relationships of sequenced A. baumannii and found no correlation between phylogeny and body site of isolation. This method identified genomic regions unique to both those isolates found on the surface of the skin or in wounds, termed colonization isolates, and those identified from body fluids, termed invasive isolates; these regions may play a role in the pathogenesis and spread of this important pathogen. A PCR-based screen of 74 A. baumanii isolates demonstrated that these unique genes are not exclusive to either phenotype or isolation source; however, a conserved genomic region exclusive to all sequenced A. baumannii was identified and verified. The results of the comparative genome analysis and PCR assay show that A. baumannii is a diverse and genomically variable pathogen that appears to have the potential to cause a range of human disease regardless of the isolation source.BMC Genomics 06/2011; 12:291. · 4.07 Impact Factor -
Article: Investigating the genome diversity of B. cereus and evolutionary aspects of B. anthracis emergence.
[show abstract] [hide abstract]
ABSTRACT: Here we report the use of a multi-genome DNA microarray to investigate the genome diversity of Bacillus cereus group members and elucidate the events associated with the emergence of Bacillus anthracis the causative agent of anthrax-a lethal zoonotic disease. We initially performed directed genome sequencing of seven diverse B. cereus strains to identify novel sequences encoded in those genomes. The novel genes identified, combined with those publicly available, allowed the design of a "species" DNA microarray. Comparative genomic hybridization analyses of 41 strains indicate that substantial heterogeneity exists with respect to the genes comprising functional role categories. While the acquisition of the plasmid-encoded pathogenicity island (pXO1) and capsule genes (pXO2) represents a crucial landmark dictating the emergence of B. anthracis, the evolution of this species and its close relatives was associated with an overall shift in the fraction of genes devoted to energy metabolism, cellular processes, transport, as well as virulence.Genomics 03/2011; 98(1):26-39. · 3.02 Impact Factor -
Article: Bacillus anthracis comparative genome analysis in support of the Amerithrax investigation.
[show abstract] [hide abstract]
ABSTRACT: Before the anthrax letter attacks of 2001, the developing field of microbial forensics relied on microbial genotyping schemes based on a small portion of a genome sequence. Amerithrax, the investigation into the anthrax letter attacks, applied high-resolution whole-genome sequencing and comparative genomics to identify key genetic features of the letters' Bacillus anthracis Ames strain. During systematic microbiological analysis of the spore material from the letters, we identified a number of morphological variants based on phenotypic characteristics and the ability to sporulate. The genomes of these morphological variants were sequenced and compared with that of the B. anthracis Ames ancestor, the progenitor of all B. anthracis Ames strains. Through comparative genomics, we identified four distinct loci with verifiable genetic mutations. Three of the four mutations could be directly linked to sporulation pathways in B. anthracis and more specifically to the regulation of the phosphorylation state of Spo0F, a key regulatory protein in the initiation of the sporulation cascade, thus linking phenotype to genotype. None of these variant genotypes were identified in single-colony environmental B. anthracis Ames isolates associated with the investigation. These genotypes were identified only in B. anthracis morphotypes isolated from the letters, indicating that the variants were not prevalent in the environment, not even the environments associated with the investigation. This study demonstrates the forensic value of systematic microbiological analysis combined with whole-genome sequencing and comparative genomics.Proceedings of the National Academy of Sciences 03/2011; 108(12):5027-32. · 9.68 Impact Factor -
Article: Functional and phylogenetic analysis of ureD in Shiga toxin-producing Escherichia coli.
[show abstract] [hide abstract]
ABSTRACT: Enterohemorrhagic Escherichia coli (EHEC) is a food-borne pathogen that can cause severe health complications and utilizes a much lower infectious dose than other E. coli pathotypes. Despite having an intact ure locus, ureDABCEFG, the majority of EHEC strains are phenotypically urease negative under tested conditions. Urease activity potentially assists with survival fitness by enhancing acid tolerance during passage through the stomach or by aiding with colonization in either human or animal reservoirs. Previously, in the EHEC O157:H7 Sakai strain, a point mutation in ureD, encoding a urease chaperone protein, was identified, resulting in a substitution of an amber stop codon for glutamine. This single nucleotide polymorphism (SNP) is observed in the majority of EHEC O157:H7 isolates and correlates with a negative urease phenotype in vitro. We demonstrate that the lack of urease activity in vitro is not solely due to the amber codon in ureD. Our analysis has identified two additional SNPs in ureD affecting amino acid positions 38 and 205, in both cases determining whether the encoded amino acid is leucine or proline. Phylogenetic analysis based on Ure protein sequences from a variety of urease-encoding bacteria demonstrates that the proline at position 38 is highly conserved among Gram-negative bacteria. Experiments reveal that the L38P substitution enhances urease enzyme activity; however, the L205P substitution does not. Multilocus sequence typing analysis for a variety of Shiga toxin-producing E. coli isolates combined with the ureD sequence reveals that except for a subset of the O157:H7 strains, neither the in vitro urease-positive phenotype nor the ureD sequence is phylogenetically restricted.Journal of bacteriology 02/2011; 193(4):875-86. · 3.94 Impact Factor -
Article: Genomic characterization of asymptomatic Escherichia coli isolated from the neobladder.
[show abstract] [hide abstract]
ABSTRACT: The replacement of the bladder with a neobladder made from ileal tissue is the prescribed treatment in some cases of bladder cancer or trauma. Studies have demonstrated that individuals with an ileal neobladder have recurrent colonization by Escherichia coli and other species that are commonly associated with urinary tract infections; however, pyelonephritis and complicated symptomatic infections with ileal neobladders are relatively rare. This study examines the genomic content of two E. coli isolates from individuals with neobladders using comparative genomic hybridization (CGH) with a pan-E. coli/Shigella microarray. Comparisons of the neobladder genome hybridization patterns with reference genomes demonstrate that the neobladder isolates are more similar to the commensal, laboratory-adapted E. coli and a subset of enteroaggregative E. coli than they are to uropathogenic E. coli isolates. Genes identified by CGH as exclusively present in the neobladder isolates among the 30 examined isolates were primarily from large enteric isolate plasmids. Isolations identified a large plasmid in each isolate, and sequencing confirmed similarity to previously identified plasmids of enteric species. Screening, via PCR, of more than 100 isolates of E. coli from environmental, diarrhoeagenic and urinary tract sources did not identify neobladder-specific genes that were widely distributed in these populations. These results taken together demonstrate that the neobladder isolates, while distinct, are genomically more similar to gastrointestinal or commensal E. coli, suggesting why they can colonize the transplanted intestinal tissue but rarely progress to acute pyelonephritis or more severe disease.Microbiology 01/2011; 157(Pt 4):1088-102. · 3.06 Impact Factor
Top co-authors
Top Journals
Institutions
-
2012
-
Walter Reed Army Institute of Research
Silver Spring, MD, USA -
Harvard University
- Department of Microbiology and Molecular Genetics
Boston, MA, USA
-
-
2011–2012
-
University of Maryland-School of Medicine
Baltimore, MD, USA
-
-
2004–2012
-
University of Maryland, Baltimore
- • Institute for Genome Sciences
- • Department of Microbiology and Immunology
Baltimore, MD, USA -
Centers for Disease Control and Prevention
Atlanta, MI, USA
-
-
2005–2011
-
University of Texas Southwestern Medical Center
- Department of Microbiology
Dallas, TX, USA -
University of Utah
- Department of Medicinal Chemistry
Salt Lake City, UT, USA
-
-
2007–2010
-
University of Michigan
- Department of Microbiology and Immunology
Ann Arbor, MI, USA -
J. Craig Venter Institute
Rockville, MD, USA
-
-
2004–2005
-
St Joseph Medical Center (MD, USA)
Towson, MD, USA
-
