Role of Enteroaggregative Escherichia coli Virulence Factors in Uropathogenesis

ABSTRACT A multiresistant clonal Escherichia coli O78:H10 strain qualifying molecularly as enteroaggregative Escherichia coli (EAEC) was recently shown to be the cause of a community-acquired outbreak of urinary tract infection (UTI) in greater Copenhagen, Denmark, in 1991. This marks the first time EAEC has been associated with an extraintestinal disease outbreak. Importantly, the outbreak isolates were recovered from the urine of patients with symptomatic UTI, strongly implying urovirulence. Here, we sought to determine the uropathogenic properties of the Copenhagen outbreak strain and whether these properties are conferred by the EAEC-specific virulence factors. We demonstrated that through expression of aggregative adherence fimbriae, the principal adhesins of EAEC, the outbreak strain exhibited pronouncedly increased adherence to human bladder epithelial cells compared to prototype uropathogenic strains. Moreover, the strain was able to produce distinct biofilms on abiotic surfaces, including urethral catheters. These findings suggest that EAEC-specific virulence factors increase uropathogenicity and may have played a significant role in the ability of the strain to cause a community-acquired outbreak of UTI. Thus, inclusion of EAEC-specific virulence factors is warranted in future detection and characterization of uropathogenic E. coli.

[1]  J. Nataro,et al.  Characterization of the AggR Regulon in Enteroaggregative Escherichia coli , 2012, Infection and Immunity.

[2]  J. Nataro,et al.  Enteroaggregative Escherichia coli O78:H10, the Cause of an Outbreak of Urinary Tract Infection , 2012, Journal of Clinical Microbiology.

[3]  J. Nataro,et al.  The fimbriae of enteroaggregative Escherichia coli induce epithelial inflammation in vitro and in a human intestinal xenograft model. , 2012, The Journal of infectious diseases.

[4]  C. Struve,et al.  Biofilm formation of Klebsiella pneumoniae on urethral catheters requires either type 1 or type 3 fimbriae , 2012, FEMS immunology and medical microbiology.

[5]  E. Denamur,et al.  Virulence of Escherichia coli Clinical Isolates in a Murine Sepsis Model in Relation to Sequence Type ST131 Status, Fluoroquinolone Resistance, and Virulence Genotype , 2012, Infection and Immunity.

[6]  C. Struve,et al.  Enteroaggregative Escherichia coli promotes transepithelial migration of neutrophils through a conserved 12‐lipoxygenase pathway , 2012, Cellular microbiology.

[7]  James H. Bullard,et al.  Origins of the E. coli strain causing an outbreak of hemolytic-uremic syndrome in Germany. , 2011, The New England journal of medicine.

[8]  F. Ruiz-Perez,et al.  Serine protease autotransporters from Shigella flexneri and pathogenic Escherichia coli target a broad range of leukocyte glycoproteins , 2011, Proceedings of the National Academy of Sciences.

[9]  T. Dallman,et al.  Enteroaggregative E. coli O104 from an outbreak of HUS in Germany 2011, could it happen again? , 2011, Journal of infection in developing countries.

[10]  A. Nazemi,et al.  Distribution of Pathogenic Genes aatA, aap, aggR, among Uropathogenic Escherichia coli (UPEC) and Their Linkage with StbA Gene , 2011, Indian Journal of Microbiology.

[11]  J. Nataro,et al.  Enteroaggregative Escherichia coli Disrupts Epithelial Cell Tight Junctions , 2010, Infection and Immunity.

[12]  U. Römling,et al.  Characteristics of Biofilms from Urinary Tract Catheters and Presence of Biofilm-Related Components in Escherichia coli , 2010, Current Microbiology.

[13]  C. Struve,et al.  Identification of a Conserved Chromosomal Region Encoding Klebsiella pneumoniae Type 1 and Type 3 Fimbriae and Assessment of the Role of Fimbriae in Pathogenicity , 2009, Infection and Immunity.

[14]  I. Henderson,et al.  The Pic Protease of Enteroaggregative Escherichia coli Promotes Intestinal Colonization and Growth in the Presence of Mucin , 2009, Infection and Immunity.

[15]  F. Ruiz-Perez,et al.  Short report: high prevalence of serine protease autotransporter cytotoxins among strains of enteroaggregative Escherichia coli. , 2009, The American journal of tropical medicine and hygiene.

[16]  S. Woo,et al.  Comparison of Escherichia coli uropathogenic genes (kps, usp and ireA) and enteroaggregative genes (aggR and aap) via multiplex polymerase chain reaction from suprapubic urine specimens of young children with fever , 2009, Scandinavian journal of urology and nephrology.

[17]  M. Kaufmann,et al.  UK epidemic Escherichia coli strains A-E, with CTX-M-15 beta-lactamase, all belong to the international O25:H4-ST131 clone. , 2008, The Journal of antimicrobial chemotherapy.

[18]  C. Vincent,et al.  Endemic and Epidemic Lineages of Escherichia coli that Cause Urinary Tract Infections , 2008, Emerging infectious diseases.

[19]  J. Nataro,et al.  New Adhesin of Enteroaggregative Escherichia coli Related to the Afa/Dr/AAF Family , 2008, Infection and Immunity.

[20]  J. Blanco,et al.  Uropathogenic Escherichia coli (UPEC) strains may carry virulence properties of diarrhoeagenic E. coli. , 2008, FEMS immunology and medical microbiology.

[21]  D. Stickler,et al.  Species interactions in mixed-community crystalline biofilms on urinary catheters. , 2007, Journal of medical microbiology.

[22]  Viktoria Hancock,et al.  Specific selection for virulent urinary tract infectious Escherichia coli strains during catheter-associated biofilm formation. , 2007, FEMS immunology and medical microbiology.

[23]  J. Parkhill,et al.  Proteomic and microarray characterization of the AggR regulon identifies a pheU pathogenicity island in enteroaggregative Escherichia coli , 2006, Molecular microbiology.

[24]  J. Nataro,et al.  Aggregative adherence fimbriae contribute to the inflammatory response of epithelial cells infected with enteroaggregative Escherichia coli , 2005, Cellular microbiology.

[25]  J. Nataro.  Enteroaggregative Escherichia coli pathogenesis , 2005, Current opinion in gastroenterology.

[26]  Harry L. T. Mobley,et al.  Pathogenic Escherichia coli , 2004, Nature Reviews Microbiology.

[27]  D. Rasko,et al.  Autotransporter Genes pic and tsh Are Associated with Escherichia coli Strains That Cause Acute Pyelonephritis and Are Expressed during Urinary Tract Infection , 2004, Infection and Immunity.

[28]  K. Mizuguchi,et al.  The Export of Coat Protein from Enteroaggregative Escherichia coli by a Specific ATP-binding Cassette Transporter System* , 2003, Journal of Biological Chemistry.

[29]  M. Kuskowski,et al.  Isolation and Molecular Characterization of Nalidixic Acid-Resistant Extraintestinal Pathogenic Escherichia coli from Retail Chicken Products , 2003, Antimicrobial Agents and Chemotherapy.

[30]  L. Bret,et al.  Indole can act as an extracellular signal to regulate biofilm formation of Escherichia coli and other indole-producing bacteria. , 2003, Canadian journal of microbiology.

[31]  A. Schaeffer.  Global molecular epidemiology of the O15:K52:H1 extraintestinal pathogenic Escherichia coli clonal group: evidence of distribution beyond Europe. , 2003, The Journal of urology.

[32]  I. Henderson,et al.  A novel dispersin protein in enteroaggregative Escherichia coli. , 2002, The Journal of clinical investigation.

[33]  Harry L. T. Mobley,et al.  Sat, the Secreted Autotransporter Toxin of Uropathogenic Escherichia coli, Is a Vacuolating Cytotoxin for Bladder and Kidney Epithelial Cells , 2002, Infection and Immunity.

[34]  J. Nataro,et al.  Roles for Fis and YafK in biofilm formation by enteroaggregative Escherichia coli , 2001, Molecular microbiology.

[35]  C. d’Enfert,et al.  A rapid method for efficient gene replacement in the filamentous fungus Aspergillus nidulans. , 2000, Nucleic acids research.

[36]  H. Mobley,et al.  Identification of Sat, an autotransporter toxin produced by uropathogenic Escherichia coli , 2000, Molecular microbiology.

[37]  B. Wanner,et al.  One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[38]  C. Struve,et al.  Development of a Long-Term Ascending Urinary Tract Infection Mouse Model for Antibiotic Treatment Studies , 2000, Antimicrobial Agents and Chemotherapy.

[39]  D. Magde,et al.  Activation of soluble guanylate cyclase by carbon monoxide and nitric oxide: a mechanistic model. , 1999, Methods.

[40]  T Ezaki,et al.  Laboratory investigation of enteroaggregative Escherichia coli O untypeable:H10 associated with a massive outbreak of gastrointestinal illness , 1997, Journal of clinical microbiology.

[41]  T. Cheasty,et al.  Enteroaggregative Escherichia coli and outbreaks of gastroenteritis in UK , 1997, The Lancet.

[42]  N. W. Davis,et al.  The complete genome sequence of Escherichia coli K-12. , 1997, Science.

[43]  J. Nataro,et al.  T84 cells in culture as a model for enteroaggregative Escherichia coli pathogenesis , 1996, Infection and immunity.

[44]  B. Miljković-Selimović,et al.  Enteroaggregative Escherichia coli associated with an outbreak of diarrhoea in a neonatal nursery ward , 1996, Epidemiology and Infection.

[45]  J. R. Johnson,et al.  A novel multiply primed polymerase chain reaction assay for identification of variant papG genes encoding the Gal(alpha 1-4)Gal-binding PapG adhesins of Escherichia coli. , 1996, The Journal of infectious diseases.

[46]  M. Levine,et al.  Heterogeneity of enteroaggregative Escherichia coli virulence demonstrated in volunteers. , 1995, The Journal of infectious diseases.

[47]  J. Nataro,et al.  AggR, a transcriptional activator of aggregative adherence fimbria I expression in enteroaggregative Escherichia coli , 1994, Journal of bacteriology.

[48]  T. Yamamoto,et al.  Characteristics of adherence of enteroaggregative Escherichia coli to human and animal mucosa , 1991, Infection and immunity.

[49]  H. Mobley,et al.  Pyelonephritogenic Escherichia coli and killing of cultured human renal proximal tubular epithelial cells: role of hemolysin in some strains , 1990, Infection and immunity.

[50]  M. Levine,et al.  Detection of an adherence factor of enteropathogenic Escherichia coli with a DNA probe. , 1985, The Journal of infectious diseases.

[51]  V. Cabelli,et al.  Relationship between the mouse colonizing ability of a human fecal Escherichia coli strain and its ability to bind a specific mouse colonic mucous gel protein , 1983, Infection and immunity.

[52]  H. Boyer,et al.  A complementation analysis of the restriction and modification of DNA in Escherichia coli. , 1969, Journal of molecular biology.

[53]  J. Nataro,et al.  Pathogenesis of enteroaggregative Escherichia coli infection. , 2006, FEMS microbiology letters.

[54]  D. Stickler,et al.  Simple physical model to study formation and physiology of biofilms on urethral catheters. , 1999, Methods in enzymology.

[55]  B. Christensen,et al.  Molecular tools for study of biofilm physiology. , 1999, Methods in enzymology.

[56]  H. J. Kolmos,et al.  Cluster of multiresistant Escherichia coli O78:H10 in Greater Copenhagen. , 1994, Scandinavian journal of infectious diseases.