Origins and virulence mechanisms of uropathogenic Escherichia coli.

Strains of uropathogenic E. coli (UPEC) are the primary cause of urinary tract infections, including both cystitis and pyelonephritis. These bacteria have evolved a multitude of virulence factors and strategies that facilitate bacterial growth and persistence within the adverse settings of the host urinary tract. Expression of adhesive organelles like type 1 and P pili allow UPEC to bind and invade host cells and tissues within the urinary tract while expression of iron-chelating factors (siderophores) enable UPEC to pilfer host iron stores. Deployment of an array of toxins, including hemolysin and cytotoxic necrotizing factor 1, provide UPEC with the means to inflict extensive tissue damage, facilitating bacterial dissemination as well as releasing host nutrients and disabling immune effector cells. These toxins also have the capacity to modulate, in more subtle ways, host signaling pathways affecting myriad processes, including inflammatory responses, host cell survival, and cytoskeletal dynamics. Here, we discuss the mechanisms by which these and other virulence factors promote UPEC survival and growth within the urinary tract. Comparisons are also made between UPEC and other strains of extraintestinal pathogenic E. coli that, although closely related to UPEC, are distinct in their abilities to colonize the host and cause disease.

[1]  Betsy Foxman,et al.  Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. , 2002, The American journal of medicine.

[2]  Kelly J. Wright,et al.  Uropathogenic Escherichia coli Flagella Aid in Efficient Urinary Tract Colonization , 2005, Infection and Immunity.

[3]  Viktoria Hancock,et al.  Biofilm formation by asymptomatic and virulent urinary tract infectious Escherichia coli strains. , 2007, FEMS microbiology letters.

[4]  James R. Johnson,et al.  Concurrent fecal colonization with extraintestinal pathogenic Escherichia coli in a homosexual man with recurrent urinary tract infection and in his male sex partner. , 2002, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[5]  J. Hacker,et al.  Molecular Basis of Commensalism in the Urinary Tract: Low Virulence or Virulence Attenuation? , 2007, Infection and Immunity.

[6]  A. Hall,et al.  Rho GTPases in cell biology , 2002, Nature.

[7]  L. Mashburn-Warren,et al.  Special delivery: vesicle trafficking in prokaryotes , 2006, Molecular microbiology.

[8]  L. Wieler,et al.  [Avian pathogenic Escherichia coli (APEC)]. , 2003, Berliner und Munchener tierarztliche Wochenschrift.

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

[10]  F. Goñi,et al.  Interaction of the bacterial protein toxin α‐haemolysin with model membranes: protein binding does not always lead to lytic activity , 1995, FEBS letters.

[11]  B. Uhlin,et al.  Regulatory cross‐talk between adhesin operons in Escherichia coli: inhibition of type 1 fimbriae expression by the PapB protein , 2000, The EMBO journal.

[12]  Richard Bauer,et al.  Uropathogenic Escherichia coli are more likely than commensal E. coli to be shared between heterosexual sex partners. , 2002, American journal of epidemiology.

[13]  H. Verbrugh,et al.  Role of Escherichia coli K capsular antigens during complement activation, C3 fixation, and opsonization , 1979, Infection and immunity.

[14]  G. Ulett,et al.  Asymptomatic bacteriuria Escherichia coli strain 83972 carries mutations in the foc locus and is unable to express F1C fimbriae. , 2006, Microbiology.

[15]  S. Normark,et al.  Host‐specificity of uropathogenic Escherichia coli depends on differences in binding specificity to Gal alpha 1‐4Gal‐containing isoreceptors. , 1990, The EMBO journal.

[16]  I. Henderson,et al.  Type V Protein Secretion Pathway: the Autotransporter Story , 2004, Microbiology and Molecular Biology Reviews.

[17]  P. Humphrey,et al.  Detection of Intracellular Bacterial Communities in Human Urinary Tract Infection , 2007, PLoS medicine.

[18]  P. Sansonetti,et al.  Calcium signalling during cell interactions with bacterial pathogens , 2004, Biology of the cell.

[19]  H. Mobley,et al.  Coordinate Expression of Fimbriae in Uropathogenic Escherichia coli , 2005, Infection and Immunity.

[20]  H. Mobley,et al.  Role of P-fimbrial-mediated adherence in pyelonephritis and persistence of uropathogenic Escherichia coli (UPEC) in the mammalian kidney. , 2007, Kidney international.

[21]  C. Merril,et al.  Escherichia coli K1's Capsule Is a Barrier to Bacteriophage T7 , 2005, Applied and Environmental Microbiology.

[22]  W. Seeger,et al.  The hemolysin of escherichia coli , 1988, European Journal of Epidemiology.

[23]  C. Buchrieser,et al.  How to become a uropathogen: Comparative genomic analysis of extraintestinal pathogenic Escherichia coli strains , 2006, Proceedings of the National Academy of Sciences.

[24]  D. Rasschaert,et al.  Extraintestinal Pathogenic Escherichia coli Strains of Avian and Human Origin: Link between Phylogenetic Relationships and Common Virulence Patterns , 2007, Journal of Clinical Microbiology.

[25]  J. Pinkner,et al.  Type 1 pilus‐mediated bacterial invasion of bladder epithelial cells , 2000, The EMBO journal.

[26]  J. L. Sundsbak,et al.  Actin‐gated intracellular growth and resurgence of uropathogenic Escherichia coli , 2006, Cellular microbiology.

[27]  R. Conran,et al.  Mutation of the Gene Encoding Cytotoxic Necrotizing Factor Type 1 (cnf1) Attenuates the Virulence of Uropathogenic Escherichia coli , 2001, Infection and Immunity.

[28]  L. Wieler,et al.  Avian pathogenic, uropathogenic, and newborn meningitis-causing Escherichia coli: how closely related are they? , 2007, International journal of medical microbiology : IJMM.

[29]  L. Pavone,et al.  Engagement of integrins as a cellular route of invasion by bacterial pathogens. , 2007, Veterinary journal.

[30]  Göran Widmalm,et al.  The structures of Escherichia coli O-polysaccharide antigens. , 2006, FEMS microbiology reviews.

[31]  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.

[32]  H. Akaza,et al.  Type 1, P and S fimbriae, and afimbrial adhesin I are not essential for uropathogenic Escherichia coli to adhere to and invade bladder epithelial cells. , 2002, FEMS immunology and medical microbiology.

[33]  G. Ulett,et al.  The Asymptomatic Bacteriuria Escherichia coli Strain 83972 Outcompetes Uropathogenic E. coli Strains in Human Urine , 2006, Infection and Immunity.

[34]  F. Blattner,et al.  Extensive mosaic structure revealed by the complete genome sequence of uropathogenic Escherichia coli , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[35]  G. Waksman,et al.  Structural basis of tropism of Escherichia coli to the bladder during urinary tract infection , 2002, Molecular microbiology.

[36]  B. Foxman,et al.  Escherichia coli mediated urinary tract infections: are there distinct uropathogenic E. coli (UPEC) pathotypes? , 2005, FEMS microbiology letters.

[37]  J. Hacker,et al.  Loss of Regulatory Protein RfaH Attenuates Virulence of Uropathogenic Escherichia coli , 2002, Infection and Immunity.

[38]  R. Strong,et al.  The neutrophil lipocalin NGAL is a bacteriostatic agent that interferes with siderophore-mediated iron acquisition. , 2002, Molecular cell.

[39]  Kelly J. Wright,et al.  Development of intracellular bacterial communities of uropathogenic Escherichia coli depends on type 1 pili , 2007, Cellular microbiology.

[40]  F. Bäckhed,et al.  Role of the Lipopolysaccharide-CD14 Complex for the Activity of Hemolysin from Uropathogenic Escherichia coli , 2006, Infection and Immunity.

[41]  S. Hultgren,et al.  Induction and evasion of host defenses by type 1-piliated uropathogenic Escherichia coli. , 1998, Science.

[42]  C. Svanborg,et al.  Type 1 fimbrial expression enhances Escherichia coli virulence for the urinary tract. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[43]  E. Nielsen,et al.  Asymptomatic bacteriuria Escherichia coli strains: adhesins, growth and competition. , 2006, FEMS microbiology letters.

[44]  U. Dobrindt,et al.  Demonstration of regulatory cross-talk between P fimbriae and type 1 fimbriae in uropathogenic Escherichia coli. , 2006, Microbiology.

[45]  W. Donovan,et al.  Urinary tract infection prophylaxis using Escherichia coli 83972 in spinal cord injured patients. , 2000, The Journal of urology.

[46]  J. Saunders,et al.  Contribution of capsular polysaccharide and surface properties to virulence of Escherichia coli K1 , 1987, Infection and immunity.

[47]  B. Bishop,et al.  TLR4-initiated and cAMP-mediated abrogation of bacterial invasion of the bladder. , 2007, Cell host & microbe.

[48]  J. R. Johnson,et al.  Virulence factors in Escherichia coli urinary tract infection , 1991, Clinical Microbiology Reviews.

[49]  J. R. Johnson,et al.  Proposal for a new inclusive designation for extraintestinal pathogenic isolates of Escherichia coli: ExPEC. , 2000, The Journal of infectious diseases.

[50]  F. Bäckhed,et al.  α-Haemolysin of uropathogenic E. coli induces Ca 2+ oscillations in renal epithelial cells , 2000, Nature.

[51]  C. Tang,et al.  Type 1 fimbriae and extracellular polysaccharides are preeminent uropathogenic Escherichia coli virulence determinants in the murine urinary tract , 2002, Molecular microbiology.

[52]  S. Bhakdi,et al.  Why Escherichia coli α‐hemolysin induces calcium oscillations in mammalian cells‐the pore is on its own , 2006, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[53]  T. Johnson,et al.  Characterizing the APEC pathotype. , 2005, Veterinary research.

[54]  S. Wai,et al.  Release of the type I secreted α‐haemolysin via outer membrane vesicles from Escherichia coli , 2006 .

[55]  N. Baker,et al.  Binding specificities of wild-type and cloned Escherichia coli strains that recognize globo-A , 1989, Infection and immunity.

[56]  A. Stapleton,et al.  Chromosomal restriction fragment length polymorphism analysis of Escherichia coli strains causing recurrent urinary tract infections in young women. , 1995, The Journal of infectious diseases.

[57]  R. Darouiche,et al.  Virulence Properties of Escherichia coli83972, a Prototype Strain Associated with Asymptomatic Bacteriuria , 1999, Infection and Immunity.

[58]  V. Parreira,et al.  A Novel Pathogenicity Island Integrated Adjacent to the thrW tRNA Gene of Avian Pathogenic Escherichia coli Encodes a Vacuolating Autotransporter Toxin , 2003, Infection and Immunity.

[59]  P. Klemm,et al.  Global Gene Expression Profiling of the Asymptomatic Bacteriuria Escherichia coli Strain 83972 in the Human Urinary Tract , 2006, Infection and Immunity.

[60]  T. Johnson,et al.  Acquisition of Avian Pathogenic Escherichia coli Plasmids by a Commensal E. coli Isolate Enhances Its Abilities To Kill Chicken Embryos, Grow in Human Urine, and Colonize the Murine Kidney , 2006, Infection and Immunity.

[61]  C. Dozois,et al.  Autotransporter-Encoding Sequences Are Phylogenetically Distributed among Escherichia coli Clinical Isolates and Reference Strains , 2007, Applied and Environmental Microbiology.

[62]  David R. Liu,et al.  The pathogen-associated iroA gene cluster mediates bacterial evasion of lipocalin 2 , 2006, Proceedings of the National Academy of Sciences.

[63]  M. Achtman,et al.  Role of the capsule and the O antigen in resistance of O18:K1 Escherichia coli to complement-mediated killing , 1983, Infection and immunity.

[64]  J Hacker,et al.  Pathogenicity islands of virulent bacteria: structure, function and impact on microbial evolution , 1997, Molecular microbiology.

[65]  D. Polk,et al.  Commensal bacteria in the gut: learning who our friends are , 2004, Current opinion in gastroenterology.

[66]  S. Langermann,et al.  Prevention of mucosal Escherichia coli infection by FimH-adhesin-based systemic vaccination. , 1997, Science.

[67]  J. Hacker,et al.  Active Cytotoxic Necrotizing Factor 1 Associated with Outer Membrane Vesicles from Uropathogenic Escherichia coli , 2006, Infection and Immunity.

[68]  A. O’Brien,et al.  Cytotoxic Necrotizing Factor Type 1 of Uropathogenic Escherichia coli Kills Cultured Human Uroepithelial 5637 Cells by an Apoptotic Mechanism , 2000, Infection and Immunity.

[69]  L. Truong,et al.  pap-2-encoded fimbriae adhere to the P blood group-related glycosphingolipid stage-specific embryonic antigen 4 in the human kidney , 1990, Infection and immunity.

[70]  B. Finlay,et al.  Pathogenicity islands: a molecular toolbox for bacterial virulence , 2006, Cellular microbiology.

[71]  I. Snyder,et al.  Effect of Escherichia coli alpha-hemolysin on human peripheral leukocyte function in vitro , 1982, Infection and Immunity.

[72]  S. Hultgren,et al.  Intracellular Bacterial Biofilm-Like Pods in Urinary Tract Infections , 2003, Science.

[73]  K. Mori,et al.  Cell biology: Iron thievery , 2004, Nature.

[74]  D. Rasko,et al.  Defining Genomic Islands and Uropathogen-Specific Genes in Uropathogenic Escherichia coli , 2007, Journal of bacteriology.

[75]  W. Rabsch,et al.  Salmochelins, siderophores of Salmonella enterica and uropathogenic Escherichia coli strains, are recognized by the outer membrane receptor IroN , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[76]  M. Kuehn,et al.  Bacterial outer membrane vesicles and the host-pathogen interaction. , 2005, Genes & development.

[77]  J. L. Sundsbak,et al.  Integrin-Mediated Host Cell Invasion by Type 1–Piliated Uropathogenic Escherichia coli , 2007, PLoS pathogens.

[78]  E. Bingen,et al.  Combined multilocus sequence typing and O serogrouping distinguishes Escherichia coli subtypes associated with infant urosepsis and/or meningitis. , 2007, The Journal of infectious diseases.

[79]  T. J. Wiles,et al.  Inactivation of host Akt/protein kinase B signaling by bacterial pore-forming toxins. , 2008, Molecular biology of the cell.

[80]  S. Andrews,et al.  Bacterial iron homeostasis. , 2003, FEMS microbiology reviews.

[81]  Hening Lin,et al.  How pathogenic bacteria evade mammalian sabotage in the battle for iron , 2006, Nature chemical biology.

[82]  S. Hakomori,et al.  The Globoseries Glycosphingolipid Sialosyl Galactosyl Globoside Is Found in Urinary Tract Tissues and Is a Preferred Binding Receptor In Vitro for Uropathogenic Escherichia coli Expressing pap-Encoded Adhesins , 1998, Infection and Immunity.

[83]  S. Kariyawasam,et al.  Common and specific genomic sequences of avian and human extraintestinal pathogenic Escherichia coli as determined by genomic subtractive hybridization. , 2007, BMC microbiology.

[84]  Shizuo Akira,et al.  Lipocalin 2 mediates an innate immune response to bacterial infection by sequestrating iron , 2004, Nature.

[85]  A. Nelson,et al.  Epithelial Cells Are Sensitive Detectors of Bacterial Pore-forming Toxins* , 2006, Journal of Biological Chemistry.

[86]  E. Ron Host specificity of septicemic Escherichia coli: human and avian pathogens. , 2006, Current opinion in microbiology.

[87]  P. Cossart,et al.  Histone modifications induced by a family of bacterial toxins , 2007, Proceedings of the National Academy of Sciences.

[88]  Kelly D. Smith Iron metabolism at the host pathogen interface: lipocalin 2 and the pathogen-associated iroA gene cluster. , 2007, The international journal of biochemistry & cell biology.

[89]  K. Hantke,et al.  The structure of salmochelins: C-glucosylated enterobactins of Salmonella enterica§ , 2004, Biometals.

[90]  J. R. Johnson,et al.  Widespread distribution of urinary tract infections caused by a multidrug-resistant Escherichia coli clonal group. , 2001, The New England journal of medicine.

[91]  Curt Doetkott,et al.  The Genome Sequence of Avian Pathogenic Escherichia coli Strain O1:K1:H7 Shares Strong Similarities with Human Extraintestinal Pathogenic E. coli Genomes , 2007, Journal of bacteriology.

[92]  J. Hacker,et al.  Pathogenicity islands and the evolution of microbes. , 2000, Annual review of microbiology.

[93]  H. Mobley,et al.  Role of Motility in the Colonization of Uropathogenic Escherichia coli in the Urinary Tract , 2005, Infection and Immunity.

[94]  A. O’Brien,et al.  Cytotoxic Necrotizing Factor Type 1 Delivered by Outer Membrane Vesicles of Uropathogenic Escherichia coli Attenuates Polymorphonuclear Leukocyte Antimicrobial Activity and Chemotaxis , 2006, Infection and Immunity.

[95]  D. Eto,et al.  Covert Operations of Uropathogenic Escherichia coli within the Urinary Tract , 2005, Traffic.

[96]  H. Mobley,et al.  Protease Activity, Secretion, Cell Entry, Cytotoxicity, and Cellular Targets of Secreted Autotransporter Toxin of Uropathogenic Escherichia coli , 2006, Infection and Immunity.

[97]  Scott J. Hultgren,et al.  Functional Genomic Studies of Uropathogenic Escherichia coli and Host Urothelial Cells when Intracellular Bacterial Communities Are Assembled* , 2007, Journal of Biological Chemistry.

[98]  R. Welch,et al.  Domains of Escherichia coli hemolysin (HlyA) involved in binding of calcium and erythrocyte membranes , 1990, Infection and immunity.

[99]  R. Welch,et al.  Calcium is required for binding of Escherichia coli hemolysin (HlyA) to erythrocyte membranes , 1990, Infection and immunity.

[100]  J. Hacker,et al.  Regulatory Interactions among Adhesin Gene Systems of Uropathogenic Escherichia coli , 2007, Infection and Immunity.

[101]  M. Schembri,et al.  Mellowing Out: Adaptation to Commensalism by Escherichia coli Asymptomatic Bacteriuria Strain 83972 , 2007, Infection and Immunity.

[102]  D. Gally,et al.  Switches, cross-talk and memory in Escherichia coli adherence. , 2004, Journal of medical microbiology.

[103]  Jon R. Armstrong,et al.  Identification of genes subject to positive selection in uropathogenic strains of Escherichia coli: a comparative genomics approach. , 2006, Proceedings of the National Academy of Sciences of the United States of America.

[104]  Harry L. T. Mobley,et al.  Expression of flagella is coincident with uropathogenic Escherichia coli ascension to the upper urinary tract , 2007, Proceedings of the National Academy of Sciences.

[105]  S. Hultgren,et al.  Establishment of a Persistent Escherichia coli Reservoir during the Acute Phase of a Bladder Infection , 2001, Infection and Immunity.

[106]  G. Ulett,et al.  Molecular Characterization of the Escherichia coli Asymptomatic Bacteriuria Strain 83972: the Taming of a Pathogen , 2006, Infection and Immunity.

[107]  L. Landraud,et al.  Rho GTPase-activating bacterial toxins: from bacterial virulence regulation to eukaryotic cell biology. , 2007, FEMS microbiology reviews.

[108]  T. Johnson,et al.  Comparison of Escherichia coli isolates implicated in human urinary tract infection and avian colibacillosis. , 2005, Microbiology.

[109]  A. O’Brien,et al.  Cytotoxic Necrotizing Factor Type 1 Production by Uropathogenic Escherichia coli Modulates Polymorphonuclear Leukocyte Function , 2005, Infection and Immunity.

[110]  D. Gally,et al.  Regulation of P-Fimbrial Phase Variation Frequencies in Escherichia coli CFT073 , 2007, Infection and Immunity.

[111]  S. Hultgren,et al.  Bad bugs and beleaguered bladders: interplay between uropathogenic Escherichia coli and innate host defenses. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[112]  H. Mobley,et al.  Role of Phase Variation of Type 1 Fimbriae in a Uropathogenic Escherichia coli Cystitis Isolate during Urinary Tract Infection , 2006, Infection and Immunity.

[113]  R. Glockshuber,et al.  Uroplakin Ia is the urothelial receptor for uropathogenic Escherichia coli: evidence from in vitro FimH binding. , 2001, Journal of cell science.

[114]  K. Kim,et al.  The K1 capsule modulates trafficking of E. coli‐containing vacuoles and enhances intracellular bacterial survival in human brain microvascular endothelial cells , 2003, Cellular microbiology.

[115]  P. Boquet,et al.  CNF1 Exploits the Ubiquitin-Proteasome Machinery to Restrict Rho GTPase Activation for Bacterial Host Cell Invasion , 2002, Cell.