Abstract
Urinary tract infections (UTIs) are the commonest human bacterial infections and are responsible for substantial morbidity and mortality, resulting in increased healthcare costs. Most UTIs are caused by specialized Escherichia coli (E. coli) strains referred to as uropathogenic E. coli (UPEC). UPEC possess a variety of virulence factors (VFs), which the organism uses to attach, invade, and injure the host. These VFs include adhesins, toxins, iron acquisition factors, lipopolysacharide capsules, and other invasins. Most studies on UTI pathogenesis have targeted VFs. The source of UPEC is the host’s fecal flora. According to the pathogenicity theory, UPEC strains with special VFs move from the host’s fecal flora to the urogenital tract and cause UTI. However, another theory states that the numerically abundant strain is responsible for UTI. Effective UTI management is hampered by the recent rise in antibiotic resistance, specifically, the recent emergence of multidrug-resistant E. coli sequence type 131. The distribution of VFs and other bacterial characteristics among different patient groups and UTI syndromes, is crucial understanding UTI pathogenesis, which would guide clinical decision making. For ST131 clonal group, further epidemiological studies are needed to clarify transmission pathways, risk factors for spread, and reservoirs, so that effective control measures can be devised.
Keywords
- Escherichia coli
- urinary tract infections
- virulence factors
- multidrug resistance
1. Introduction
Urinary tract infections (UTIs) are an important medical problem, being the second most common bacterial infection of humans after respiratory tract infection. They are often recurrent, frequently difficult to treat, and can cause parenchymal damage to the kidney, leading to renal insufficiency and further complications [1–3]. UTIs impose a substantial burden on society and the health care system in relation to diagnosis, management, lost productivity, morbidity, and sometimes death [4–6]. Furthermore, increasing resistance to therapeutically important antimicrobial agents and the recent emergence of the virulent and multidrug-resistant ST131 clonal group have made UTI management progressively more costly and challenging [7, 8]. Several studies suggest that a greater array of VFs is generally needed to cause more invasive UTIs, although the extent appears to differ according to age and gender. Thus, further studies targeting VFs, which have been proposed as the best target for vaccine development, are needed. A better understanding of UTI pathogenesis, especially for the most common cause of UTI, namely
2. Etiology of UTI
UTIs are mainly caused by bacteria, although fungi and some viruses have also been implicated. Among bacteria, Gram-negative bacteria of the
3. Epidemiology and risk factors for E. coli UTI
Overall, UTI is more prevalent among females than males, attributable to the close proximity of the urogenital tract to the anus in females, the greater length of the male urethra, and the antibacterial activity of prostatic fluid in men [12, 13]. Functional, hormonal, and anatomical changes that occur during pregnancy predispose pregnant women to UTI [14]. UTI during pregnancy can result in devastating maternal and neonatal complications, including maternal sepsis, preterm labor, and premature delivery [14]. Thirty percent of patients with untreated asymptomatic bacteriuria (ASB) develop symptomatic cystitis and up to 50% develop pyelonephritis [13]. ASB is also associated with intrauterine growth retardation and low-birth-weight infants [13]. Up to 27% of preterm births have been associated with UTI in pregnancy [14].
Among bacterial infections in children, UTI ranks highly, even outnumbering bacterial meningitis, pneumonia, and bacteremia [15]. About 1% of infants < 3 months old develop UTI, with more males affected than females. Proper and urgent UTI management is crucial in children as an estimated 10–15% of children with UTI will develop permanent kidney damage, leading to other chronic diseases such as hypertension and renal insufficiency [16, 17].
The propensity of UTIs to recur, often within a few weeks or months after an initial acute infection, is a problem in UTI management. Approximately 20–30% of women will have a recurrent bladder infection within 6 months after an initial episode, and an additional 3% will experience a third infection [18, 19].
4. E. coli UTI pathogenesis
UTI pathogenesis is a complex process that is influenced by various host biological and behavioral factors, and by properties of the infecting pathogen, including VFs. This presents a challenge in epidemiological studies regarding the role of specific VFs in UTI pathogenesis because of the confounding effect of host factors.
In most noncompromised individuals, the urinary tract is normally sterile, and the entry of exogenous microorganisms is prevented by urine flow, secreted and tissue-associated antibacterial factors, and the bactericidal activities of effector immune cells. In most cases, the host fecal flora is the source of the infecting
Although the host’s fecal flora is the major source of the
5. Uropathogenic E. coli (UPEC) and virulence factors (VFs)
Virulence refers to the ability of an organism to cause disease, and is a function of the presence of distinct accessory traits, referred to as virulence factors (VFs). VFs are specific properties that enable organisms to overcome host defenses and cause disease [26]. However, although several VFs have been identified in UPEC, experimental and epidemiological data have shown that none uniquely defines these pathogens.
UPEC VFs are grouped by functional categories as adhesins, toxins, iron acquisition systems, and protectins. VFs are encoded by genes located on chromosomes or plasmids, with some being exclusively chromosomal (e.g.,
6. Structure of adhesins
Adhesins, which appear as hair-like fibers called fimbriae (or pili), facilitate the colonization with
Various adhesins have been identified and are classified mainly according to receptor specificity, with some being mannose resistant and others sensitive. P fimbriae (or pili), the best-described group of mannose-resistant adhesins of UPEC, are so named because they specifically bind to the Gal(α1–4) Gal disaccharide galabiose, which is an antigen within the human P blood group system [26]. Different components of the P fimbriae have been described, including four different units that are at the tip of the fibrillum, including PapG, PapE, PapF, and PapK [28–30]. These fimbrial proteins and other accessory proteins are encoded by a chromosomal multicistronic gene cluster termed
Actual attachment of the organism to host epithelial cells is effected through PapG by recognition of glycolipid receptors expressed on host kidney cells and red blood cells [32]. Three variants of PapG, encoded by distinct alleles of the corresponding gene,
Type 1 fimbriae are the commonest adhesive organelles of
Phase variation controls the expression of type 1 fimbriae by site specific recombination. A 314-bp phase-variable invertible element, that contains the promoter, controls the transcription of the fimbrial genes fimACDFGH. The promoter drives the expression of type 1 fimbriae when the switch is in the ON orientation but not when it is in the OFF orientation [40]. It has been shown that the expression of type 1 fimbriae coordinately affects the expression of P fimbriae in an inverse manner, providing evidence of a direct communication between genes related to pathogenesis [41, 42].
Although most studies have confirmed that type 1 fimbriae are particularly important in bladder colonization [43, 44], the proportions of UPEC strains from urine and feces expressing type 1 fimbriae appear to be similar [26], ranging from a high of 71% among isolates from cystitis patients to a low of 58% among those from patients with ASB, with fecal strains in the mid-range at 60% [26]. However, in contrast, the level of expression of type 1 fimbriae among UPEC blood isolates (81%) is significantly different from that of fecal strains [45, 46].
Another adhesin family is the Afa/Dr family, which consists of adhesins that include the uropathogen-associated fimbrial adhesin Dr, along with other nonfimbrial adhesins, including Afa-1, Afa-2, Afa-3, Afa 4, NFu1, and Dr-11. These adhesins have a different structure from other
Finally, the closely-related S fimbriae and F1C (fimbriae of serotype 1C), so named because of their binding specificity for terminal sialyl-galactoside residues, mediate X-type mannose resistant hemagglutination of human erythrocytes [51–53]. They agglutinate human and bovine red cells [54, 55]. S fimbriae have a similar, but less well defined, structure to both type 1 and P fimbriae. Just like type 1 and P fimbriae, expression of S fimbriae exhibits phase variation [51]. Binding sites for S fimbriae are located on epithelial cells of the proximal and distal tubules, collecting ducts and glomerulus [55]. In humans, S-fimbriated
7. Iron acquisition systems for UPEC
Bacteria and the host compete for available iron, which is needed for oxygen transport and storage, DNA synthesis, electron transport, and metabolism of peroxides [57, 58]. Pathogenic bacteria, including UPEC, have devised ways of accessing iron by producing siderophore-mediated iron transport systems. UPEC exhibit multiple mechanisms for extracting iron from the host, mainly siderophore-siderophore receptor systems, but also heme uptake [59–62]. Siderophores, which are secreted low molecular weight molecules, have a high affinity for ferric (Fe3+) iron, which is insoluble as a free cation. UPEC retrieve iron-bound siderophores through receptors that facilitate the transportation of siderophore-iron complexes through the bacterial membrane and into the cytosol where the iron is concentrated and utilized. While all
Several enterobacteria contain a gene cluster called the high pathogenicity island (HPI), which encodes proteins for biosynthesis of the yersiniabactin siderophore and its uptake system [63, 64]. The HPI is widespread among members of the
Aerobactin is another important hydroxamate siderophore synthesized from the condensation of two lysine and one citrate molecules. In UPEC, the aerobactin system is encoded by a five-gene operon with four genes encoding the enzymes needed for aerobactin synthesis and a fifth encoding the outer membrane receptor protein [67, 68]. The synthesis genes are designated
Previous studies have shown that the aerobactin system and P fimbriae are commonly found together in UPEC isolates from patients with UTI and urosepsis [70, 71]. However, among urosepsis patient isolates, this association is only true for chromosomally encoded aerobactin [71]. An association of chromosomally encoded aerobactin with hemolysin among urosepsis or UTI patient isolates has also been confirmed [71]. These observations suggest that the association of aerobactin with other VFs differs between plasmid and chromosomal aerobactin. Plasmids carrying the aerobactin region sometimes also carry antimicrobial resistance genes [71–73]. The aerobactin system is found more commonly among UPEC strains from patients with pyelonephritis (73%), cystitis (49%), or bacteremia (58%) than among ASB patient isolates (38%) or fecal strains (41%), which suggest that aerobactin contributes to virulence both within and outside of the urinary tract. The association of aerobactin with more serious forms of UTI is seen specifically in infants, girls, and women [26, 9].
Finally, UPEC produce salmochelins in order to access iron during invasion of the host. The salmochelin siderophore system, so named because it was first shown to be characteristic of
8. Toxins produced by UPEC
Most hemolytic UPEC strains secrete a heat-labile cytolytic protein toxin known as alpha hemolysin [78], which is encoded by a polycistronic operon, consisting of four genes arranged in the order of hly-CADB [79]. The product of hlyC is important in the activation of the hemolytic toxin, which is the product of the
Alpha hemolysin lyses red cells of all mammals and even of fish [81], and is toxic to host cells resulting in inflammation, tissue injury, and impaired host defenses. Hemolysin stimulates super-oxide anion and hydrogen peroxide release from and oxygen consumption by renal tubular cells, including histamine release from mast cells and basophils [82, 83]. Hemolytic uropathogenic strains almost always also express P fimbriae [84]. Hemolysin production is found most commonly in UPEC strains from patients with pyelonephritis (49%), followed by cystitis isolates and ASB [85]. These data demonstrate an association of hemolysin production with invasive uropathogenic strains. UPEC strains that produce increased amounts of alpha hemolysin are also more resistant to the complement action of human serum when compared to strains that are nonhemolytic or produce reduced amounts of hemolysin [81].
UPEC also produce a toxin referred to as cytotoxic necrotising factor type 1 (CNF-1). CNF-1 is a chromosomally encoded UPEC toxin that catalyzes the glutamine deamination of the small GTPases RhoA, Rac, and Cdc 42 [86], leading to the disturbance of numerous eukaryotic cellular functions including formation of actin stress fibers, lamellipodia, filopodia, and modulation of inflammatory signaling pathways [87, 88].
Yamamoto et al. showed that 61% of UTI isolates and 38% of bacteremia isolates produced CNF-1 as opposed to only 10% of commensal fecal isolates [89]. Of these isolates, approximately 98% that produced CNF-1 also produced hemolysin. Studies by Mitsumori et al. showed a CNF-1 prevalence of 64% among UPEC isolates from prostatitis and 36% from pyelonephritis. These results suggest that CNF-1 is associated with increased virulence in UTI pathogenesis. CNF-1 production may also increase the inflammatory response of the host [90]. Specifically, Elliott et al. reported that CNF-1 evokes edema and necrosis and is associated with inflammation in the intestines of rabbits in a diarrhea model of infection [90]. Human neutrophils have been observed to be less effective at killing CNF-1 positive, than CNF-1 negative bacteria.
9. Protectins
UPEC also express outer membrane proteins, such as traT and Iss, which may enhance serum resistance through avoidance of complement killing [26]. Bacteria are killed by normal human serum through the lytic activity of the complement system [91]. The alternative pathway is activated by bacteria in the absence of specific antibody and plays a more important role in serum killing than the classic pathway [92]. Resistance of
Although the K1 capsule is important in certain strains, other mechanisms appear to be more significant determinants of serum resistance in some populations of
9.1. Outer membrane protease T
Outer membrane protease T (OmpT) of
9.2. Uropathogenic specific protein
Uropathogenic specific protein (Usp) in
10. Biofilm production by UPEC
Biofilm production by
Curli belong to a class of fibers known as amyloids and are involved in adhesion to surfaces, cell aggregation and, finally, biofilm development. Curli fibers are encoded in the curling subunit gene (
Co-expression of curli and cellulose tends to decrease in prevalence from more severe to less severe UTI, then to commensal isolates, suggesting that biofilm may facilitate progression from the lower to upper urinary tract [110]. Furthermore, co-expression of both biofilm components is associated with a high prevalence of individual VF genes, high VF scores, and phylogenetic group B2, consistent with heightened urovirulence of such strains. Notably, there may be an interaction between classic VFs and biofilm formation. For example, in one study, all isolates that co-expressed both biofilm components also harbored fyuA, implying that iron uptake via the yersiniabactin system may play a significant role in biofilm growth [64]. Additionally, recent studies have shown that the biofilm components, curli fimbriae and cellulose, also play important roles in adhesion, invasion, and long-term survival of UPEC within the host urinary tract [110, 111].
11. Phylogenetic group and VF distribution among patient groups and clinical syndromes
UTI syndrome-specific differences among
In most patient groups, pyelonephritis isolates tend to exhibit the highest prevalences of many individual VFs, have the highest VF scores, and are the most likely to belong to phylogenetic group B2, ST131, and a UTI-associated O type. The reported higher prevalence of pap operon genes (encoding P fimbriae) in pyelonephritis than cystitis isolates correlates with increased tropism for the kidney of P fimbriated strains [121, 123]. papGII has been shown, experimentally, to contribute to pathogenesis of pyelonephritis [124, 125], and OmpT is strongly associated with febrile UTI in men [122, 126]. However, it is not clear whether these VFs act individually or in concert with other known or unknown VFs in causing pyelonephritis.
In men and women, although cystitis and pyelonephritis isolates differ in inferred molecular virulence, phylogenetic group distribution is similar between the two clinical syndromes. However, within each phylogenetic group, VF scores exhibit a gradient across source groups (fecal < cystitis < pyelonephritis), suggesting the presence of different virulence strata within each phylogenetic group, with more virulent strains selectively causing pyelonephritis and less virulent strains being associated with cystitis and fecal isolates in that order. This suggests that VF repertoire is as, or more, important than phylogenetic background for predicting pathogenic behavior in UPEC [122, 127].
Although cystitis and pyelonephritis isolates differ significantly in inferred virulence in various patient groups, no single VF profile is unique to any clinical syndrome or patient group, implying that UTI pathogenesis is multiply determined, as suggested by several previous studies [122, 128]. Thus, intervention strategies based on VF genes might have to involve multiple targets, which would offer the extra advantage of protection against a wide range of UTI syndromes.
12. Transmission of VFs
The genes encoding specific UPEC VFs can be exclusively chromosomal (e.g.,
13. Antimicrobial drugs and uropathogenic Escherichia coli
Managing UTI caused by UPEC has become challenging over the years due to increasing resistance to the commonly used antibiotics [135–139], which poses a great threat to future capacity to treat UTI caused by UPEC. Although TMP-SMX has traditionally been used as a first-line treatment for UTI [140], there are reports of increased resistance to this antibiotic, which in some countries is in the range 15–20% [137]. Many UPEC strains resistant to TMP-SMZ are also resistant to amoxicillin and cephalexin. Nitrofurantoin remains highly effective against UPEC, but is mainly used for cystitis treatment due to its inability to attain sufficient serum levels to treat invasive or systemic infections [137], and all have excellent bioavailability and achieve high urinary concentrations. However, increased FQ use has resulted in a rise in the prevalence of resistance, and FQ-resistant
14. Relationship between antibiotic resistance and virulence or phylogenetic background in UPEC
Previous studies show that in
15. E. coli sequence type 131 (ST131)
Determining the clonal types of UPEC is crucial for understanding the role of clonal spread to emerging antimicrobial resistance, which is important for defining and interrupting transmission pathways. Multidrug-resistant
In contrast to traditional antimicrobial resistant
Most ST131 clinical isolates are FQ resistant, and many are also co-resistant to aminoglycosides and/or trimethoprim-sulfamethoxazole (TMP-SMZ). A minority produces extended-spectrum beta-lactamases (ESBLs) that confer resistance to extended-spectrum cephalosporins.
Despite limited epidemiological evidence of increased virulence of ST131, a recent study revealed that ST131 exhibits a marked prevalence gradient across source groups, from pyelonephritis to cystitis isolates, and finally to fecal isolates [126]. This is consistent with increased urovirulence, and provides epidemiological evidence of increased virulence for ST131, which has been presumed but without evidence from experimental animal models [8, 150]. The antibiotic resistance advantage, in combination with the possible presence of enhanced virulence, could explain the recent worldwide emergence of ST131. The increasing prevalence of ESBL-producing
Four VF genes (
Resistance of ST131 to extended-spectrum cephalosporins is often due to production of ESBLs. The initial descriptions of ST131 emphasized its association with CTX-M-15, but subsequent studies have shown that it is more commonly ESBL-negative but FQ-resistant [154–156]. Previous studies in Australia and Japan showed that ST131-O25b, ST131-O16, and group D-ST405 clonal groups contribute to the spread of ESBL-producing
16. Conclusions
A wide range of UPEC VFs have been established epidemiologically or experimentally (
The prevalence of antibiotic resistance among human urine
References
- 1.
Draghijeva E. Virulence factors in Escherichia coli from children with pyelonephritis. Clinical Microbiology and Infection. 1999;6 :328-333 - 2.
Leroy S, Chalumeau T, Ulinski T, et al. Impressive renal damage after acute pyelonephritis in a child. Pediatric Nephrology. 2010; 25 :1365-1368 - 3.
Prakash Kalra OM, Raizada A. Approach to a patient with urosepsis. Journal of Global Infectious Diseases. 2009; 1 :57-63 - 4.
Foxman B, Barlow R, D’Arcy H, Gillespie B, Solbel J. Urinary tract infection: Self-reported incidence and associated costs. Annals of Epidemiology. 2000; 10 :509-515 - 5.
Foxman B, Brown P. Epidemiology of urinary tract infections: Transmission and risk factors, incidence, and costs. Infectious Disease Clinics of North America. 2003; 17 :227-241 - 6.
Griebling TL. Urologic diseases in America project: Trends in resource use for urinary tract infections in men. Journal of Urology. 2005; 173 :1288-1294 - 7.
Ikram R, Rebecca Psutka R, Carter A, Priest P. An outbreak of multi-drug resistant Escherichia coli urinary tract infection in an elderly population: A case-control study of risk factors. BMC Infectious Diseases. 2015;15 :224 - 8.
Johnson JR, Porter SB, Zhanel G, Kuskowski MA, Denamur E. Virulence of Escherichia coli clinical isolates in a murine sepsis model in relation to sequence type ST131 status, fluoroquinolone resistance, and virulence genotype. Infection and Immunity. 2012;80 :1554-1562 - 9.
Ruiz J, Simon K, Horcajada JP, Velasco M, Barranco M, Roig G, Moreno-Martinez A, Martinez JA, Jimenez de Anta T, Mensa J, Vila J. Differences in virulence factors among clinical isolates of Escherichia coli causing cystitis and pyelonephritis in women and prostatitis in men. Journal of Clinical Microbiology. 2002;40 :4445-4449 - 10.
Zhang L, Foxman B. Molecular epidemiology of Escherichia coli mediated urinary tract infections. Frontiers in Bioscience. 2003;8 :e235–e244 - 11.
Johnson JR, Kuskowski MA, O'Bryan TT, Colodner R, Raz R. Virulence genotype and phylogenetic origin in relation to antibiotic resistance profile among Escherichia coli urine sample isolates from Israeli women with acute uncomplicated cystitis. Antimicrobial Agents and Chemotherapy. 2005;49 :26-31 - 12.
Lipsky BA. Urinary tract infections in men. Epidemiology, pathophysiology, diagnosis, and treatment. Annals of Internal Medicine. 1989; 110 :138-150 - 13.
Gupta K, Stamm WE. Urinary tract infections. In: Dale DC, Federman DD, editors. ACP Medicine. New York: WebMD; 2005. Section 7, chap. 23 - 14.
Ovalle A, Levancini M. Urinary tract infections in pregnancy. Current Opinion in Urology. 2001; 11 :55-59 - 15.
Wald E. Urinary tract infections in infants and children: A comprehensive overview. Current Opinion in Pediatrics. 2004; 16 :85-88 - 16.
Schlager TA. Urinary tract infections in children younger than 5 years of age: Epidemiology, diagnosis, treatment, outcomes and prevention. Paediatrics Drugs. 2001; 3 :219-227 - 17.
Chen M, Jahnukainen T, Bao W, Dare E, Ceccatelli S, Celsi G. Uropathogenic Escherichia coli toxins induce caspase-independent apoptosis in renal proximal tubules via ERK signaling. American Journal of Nephrology. 2003;23 :140-151 - 18.
Scholes D, Hooton TM, Roberts PL, Stapleton AE, Gupta K, Stamm WE. Risk factors for recurrent urinary tract infection in young women. The Journal of Infectious Diseases. 2000; 182 :1177-1182 - 19.
Eto DS, Jones TA, Sundsbak JL, Mulvey MA. Integrin-mediated host cell invasion by type-1piliated uropathogenic E. coli . PLos Pathogens. 2007;3 :e100, 0949-0960 - 20.
Moreno E, Andreu A, Perez T, Sabate M, Johnson JR, Prats G. Relationship between Escherichia coli strains causing urinary tract infection in women and the dominant faecal flora of the same hosts. Epidemiology and Infection. 2006;134 :1015-1023 - 21.
Moreno E, Andreu A, Pigrau C, Kuskowski MA, Johnson JR, Prats G. Relationship between Escherichia coli strains causing acute cystitis in women and the fecalE. coli population of the host. Journal of Clinical Microbiology. 2008;46 :2529-2534 - 22.
Manges AR, Johnson JR, Foxman B, O’Bryan TT, Fullerton KE, Riley LW. Widespread distribution of urinary tract infections caused by a multidrug-resistant Escherichia coli clonal group. The New England Journal of Medicine. 2001;345 :1007-1013 - 23.
Manges AR, Tabar H, Tellis P, Vincent C, Tellier PP. Endemic and epidemic lineages of Escherichia coli that cause urinary tract infections. Emerging Infectious Diseases. 2008;14 :1575-1583 - 24.
Pitout JD, Gregson DB, Church DL, Elsayed S, Lampland KB. Community-wide outbreaks of clonally related CTX-M-14 beta-lactamase-producing Escherichia coli strains in the Calgary health region. Journal of Clinical Microbiology. 2005;43 :2844-2849 - 25.
Svanborg C, Bergsten G, Fischer H, et al. Uropathogenic Escherichia coli as a model of host-parasite interaction. Current Opinion in Microbiology. 2005;9 :33-39 - 26.
Johnson JR. Virulence factors in Escherichia coli urinary tract infection. Clinical Microbiology Reviews. 1991;4 :80-128 - 27.
Mobley HL, Island MD, Massad G. Virulence determinants of uropathogenic Escherichia coli andProteus mirabilis . Kidney International Supplements. 1994;47 :S129-S136 - 28.
Kuehn MJ, Heuser J, Normark S, Hultgren SJ. P pili in uropathogenic E. coli are composite fibres with distinct fibrillar adhesive tips. Nature. 1992;356 :252-255 - 29.
Xiang-Qi Mu, Bullitt E. PNAS. Structure and assembly of P-pili: A protruding hinge region used for assembly of a bacterial adhesion filament. 2006; 26 :9861-9866. DOI: 10.1073_pnas.0509620103 - 30.
Antao E, Wieler LH, Ewers C. Adhesive threads of extraintestinal pathogenic Escherichia coli . A review. Gut Pathogens. 2009;1 :22 - 31.
Lane MC, Mobley HL. Role of P-fimbrial-mediated adherence in pyelonephritis and persistence of uropathogenic Escherichia coli (UPEC) in the mammalian kidney. Kidney International. 2007;72 :19-25 - 32.
Johnson JR. papG alleles amongEscherichia coli strains causing urosepsis: Associations with other bacterial characteristics and host compromise. Infection and Immunity. 1998;66 :4568-4571 - 33.
Johnson JR, Brown JJ, Maslow JN. Clonal distribution of the three alleles of the Gal (α1-4)Gal-specific adhesin gene papG amongEscherichia coli strains from patients with bacteremia. The Journal of Infectious Diseases. 1998;177 :651-661 - 34.
Manning SD, Zhang L, Foxman B, Spindler A, Tallman P, Marrs CF. Prevalence of known P-fimbrial G alleles in Escherichia coli and identification of a new adhesin class. Clinical and Diagnostic Laboratory Immunology. 2001;8 :637-640 - 35.
Flores-Mireles AL, Walker JN, Caparon M, and Hultgren SJ. Urinary tract infections: Epidemiology, mechanisms of infection and treatment options. Nature Reviews Microbiology. 2015; 13 :269-284 - 36.
O’Hanley P, Low D, Romero I, Lark D, Vosti K, Falkow S, et al. Gal-Gal binding and haemolysin phenotypes and genotypes associated with uropathogenic Escherichia coli . The New England Journal of Medicine. 1985;313 :414-420 - 37.
Sokurenko EV, Chesnokova V, Doyle RJ, Hasty DL. Diversity of the Escherichia coli type 1 fibrial lectin. Journal of Biological Chemistry. 1997;272 :17880-17886 - 38.
Sokurenko EV, Chesnokova V, Dykhuizen DE, Ofek I, Wu XR, Krogfelt KA, Struve C, Schembri MA, Hasty DL. Pathogenic adaptation of Escherichia coli by natural variation of the FimH adhesion. Proceedings of the National Academy of Sciences of the United States of America. 1998;95 :8922-8926 - 39.
Schembri MA, Klemm P. Coordinate gene regulation by fimbriae induced signal transduction. EMBO Journal. 2001; 20 :3074-3081 - 40.
Simms AN, Mobley HLT. Multiple genes repress motility in uropathogenic Escherichia coli constitutively expressing type 1 fimbriae. Journal of Bacteriology. 2008;190 :3747-3756 - 41.
Snyder JA, Hagen BJ, Lockatell CV, Maroncle N, Hagan EC, Johnson DE, Welch RA, Mobley HLT. Coordinate expression of fimbriae in uropathogenic E. coli . Infection and Immunity. 2005;73 :7588-7596 - 42.
Schwan WR, Lee JL, Lenard FA, Matthews BT, Beck MT. Osmolarity and pH growth conditions regulate fim gene transcription and type 1 pilus expression in uropathogenic Escherichia coli . Infection and Immunity. 2002;70 :1391-1402 - 43.
Hull RA, Donovan WH, Del Terzo M, Stewart C, Rogers M, and Darouiche RO. Role of Type 1 fimbria- and P fimbria-specific adherence in colonization of the neurogenic human bladder by Escherichia coli . Infection and Immunity. 2002;70 :6481-6484 - 44.
Staerk K, Khandige S, Kolmos HJ, Moeller-Jensen J, Anderson TE. Uropathogenic Escherichia coli express type 1 fimbriae only in surface adherent populations under physiological growth conditions. The Journal of Infectious Diseases. 2016;213 :386-394 - 45.
Opal SM, Gemski AS, Lyhte LW. Aerobactin and alpha-hemolysin as virulence determinants in Escherichia coli isolated from human blood, urine and stool. The Journal of Infectious Diseases. 1990;161 :794-796 - 46.
Johnson JR, Roberts PL, Stamm WE. P fimbriae and other virulence factors in Escherichia coli urosepsis: Association with patients' characteristics. The Journal of Infectious Diseases. 1987;156 :225-229 - 47.
Arthur M, Johnson CE, Rubin RH, Arbeit RD, Campanelli C, Kim C, Steinbach S, Agarwal M, Wilkinson R, Goldstein R. Molecular epidemiology of adhesin and hemolysin virulence factors among uropathogenic Escherichia coli . Infection and Immunity. 1989;57 :303-313 - 48.
Orskov I, Orskov F. Serologic classification of fimbriae. Current Topics in Microbiology and Immunology. 1990; 151 :71-90 - 49.
Nowicki B, Selavarangan R, Nowicki S. Family of Escherichia coli Dr adhesins: Decay-accelerating factor recognition and invasiveness. The Journal of Infectious Diseases. 2001;183 :524-527 - 50.
Servin, AL. Pathogenesis of Afa/Dr diffusely adhering Escherichia coli . Clinical Microbiology Reviews. 2005;18 :264-292 - 51.
Mulvey MA. Adhesion and entry of uropathogenic Escherichia coli . A mini review. Cell Microbiology. 2002;4 :257-271 - 52.
Mitsumori K, Terai A, Yamamoto S, Yoshid O. Identification of S, F1C and three PapG fimbrial adhesins in uropathogenic Escherichia coli by polymerase chain reaction. FEMS Immunology and Medical Microbiology. 1998;21 :261-268 - 53.
Khan SA, Kniep B, Oelschlaeger TA, Van Die I, Korhonen T, Hacker J. Receptor structure for F1C fimbriae of uropathogemic Escherichia coli . Infection and Immunity. 2000;68 :3541-3547 - 54.
Virkola R, Parkkinen J, Hacker J, Korhonen TK. Sialyloligosaccharide chains of laminin as an extracellular matrix target for S fimbriae of Escherichia coli . Infection and Immunity. 1993;61 :4480-4484 - 55.
Korhonen TK, Virkola R, Holthofer H. Localization of binding sites for purified Escherichia coli P fimbriae in the human kidney. Infection and Immunity. 1986;54 :328-332 - 56.
Ott M, Hacker J, Schmoll T, Jarchau T, Korhonen TK, Goebel W. Analysis of the genetic determinants coding for the S-fimbrial adhesion ( sfa ) in differentEscherichia coli strains causing meningitis or urinary tract infections. Infection and Immunity. 1986;54 :646-653 - 57.
Andrews SC, Robinson AK, Rodríguez-Quiñones F. Bacterial iron homeostasis. FEMS Microbiology Reviews. 2003; 27 :215-237 - 58.
Bagg A, Neilands JB. Ferric uptake regulation protein acts as a repressor, employing iron (II) as a cofactor to bind the operator of an iron transport operon in Escherichia coli . Biochemistry. 1987;26 :5471-5477 - 59.
Russo TA, Carlino UB, Johnson JR. Identification of ireA , a novel iron regulated virulence gene in an extraintestinal pathogenic isolate ofEscherichia coli . Infection and Immunity. 2001;69 :6209-6216 - 60.
Torres AG, Redford P, Welch RA, Payne SM. TonB-dependent systems of uropathogenic Escherichia coli : Aerobactin and heme transport and TonB are required for virulence in the mouse. Infection and Immunity. 2001;69 :6179-6185 - 61.
Watts RE, Totsika M, Challinor VL, Mabbett AN, Ulett GC, De Voss JJ, Schembri MA. Contribution of siderophore systems to growth and urinary tract colonization of asymptomatic bacteriuria Escherichia coli . Infection and Immunity. 2011;80 :333-3434 - 62.
Garcia EC, Brumbaugh AR, Mobley HLT. Redundancy and specificity of Escherichia coli iron acquisition systems during urinary tract infection. Infection and Immunity. 2011;79 :1225-1235 - 63.
Schubert S, Rakin A, Heesenman J. The Yersinia high-pathogenicity island (HPI). Evolutionary and functional aspects. International Journal of Medical Microbiology. 2004; 274 :883-894 - 64.
Hancock V, Ferrieres L, Klemm P. The ferric yersiniabactin uptake receptor fyuA is required for efficient biofilm formation by urinary tract infectionsEscherichia coli in human urine. Microbiology. 2008;154 :167-175 - 65.
Schubert S, Picard B, Gouriou AS, Heesemann J, Denamur E. Yersinia high-pathogenicity island contributes to virulence in Escherichia coli causing extraintestinal infections. Infection and Immunity. 2002;70 :5335-5337 - 66.
Hancock V, Klemm P. Global gene expression profiling of asymptomatic bacteriuria Escherichia coli during biofilm growth in human urine. Infection and Immunity. 2007;75 :966-976 - 67.
Carbonetti NH, Boonchai S, Parry SH, Väisänen-Rhen V, Korhonen TK, Williams PH. Aerobactin-mediated iron uptake by Escherichia coli isolates from human extraintestinal infections. Infection and Immunity. 1986;51 :966-968 - 68.
Crosa JH. Genetics and molecular biology of siderophore-mediated iron transport in bacteria. Microbiological Reviews. 1989; 53 :517-530 - 69.
De Lorenzo V, Bindereif A, Paw BH, Neilands JB. Aerobactin biosynthesis and transport genes of plasmid Co1V-K30 in Escherichia coli K-1. Journal of Bacteriology. 1986;165 :570-578 - 70.
Jacobson SH, Hammarlind M, Lidefeldt KJ, Osterberg E, Tullus K, Brauner A. Incidence of aerobactin-positive Escherichia coli strains in patients with symptomatic urinary tract infection. European Journal of Clinical Microbiology and Infectious Diseases. 1988;7 :630-634 - 71.
Colonna B, Nicoletti M, Visca P, Casalino M, Valenti P, Maimone F. Composite IS1 elements encoding hydroxamate-mediated iron uptake in FIme plasmids from epidemic Salmonella spp. Journal of Bacteriology. 1985;162 :307-316 - 72.
Bennett PM. Plasmid encoded antibiotic resistance: Acquisition and transfer of antibiotic resistance genes in bacteria. British Journal of Pharmacology. 2008; 153 :S347-S357 - 73.
Phillips I, Eykyn S, King A, Gransden WR, Rowe B, Frost JA, Gross RJ. Epidemic multiresistant Escherichia coli infection in West Lambeth Health District. Lancet. 1988;7 :1038-1041 - 74.
Hantke K, Nicholson G, Rabsch W, Winkelmann G. Salmochelins, siderophores of Salmonella enterica and uropathogenicEscherichia coli strains, are recognized by the outer membrane receptoriroN . Proceedings of the National Academy of Sciences of the United States of America. 2002;100 :3677-3682 - 75.
Caza M, Lepine F, Milot S, Dozois CM. Specific roles of the iroBCDEN genes in virulence of an avian pathogenicEscherichia coli O78 strain and in production of salmochelins. Infection and Immunity. 2008;76 :3539-3549 - 76.
Negre VL, Bonacorsi S, Schubert S, Bidet P, Nassif X, Bingen E. The siderophore receptor iroN but not the high-pathogenicity island or the hemin receptor chuA contributes to the bacteremic step of Escherichia coli neonatal meningitis. Infection and Immunity. 2004;72 :1216-1220 - 77.
Bauer R, Zhang L, Foxman B, Siitonen A, Jantunen M, Saxen H, Marrs C. Molecular epidemiology of 3 putative virulence genes for Escherichia coli urinary tract infection-usp, iha, and iroN (E. coli ). Journal of Infectious Diseases. 2002;185 :1521-1524 - 78.
Kucheria R, Dasgupta P, Sacks SH, Khan MS, Sheerin NS. Urinary tract infections: New insights into a common problem. Postgraduate Medical Journal. 2005; 81 :83-86 - 79.
Burgos Y, Benton L. Common origin of plasmid encoded alpha-hemolysin genes in Escherichia coli . BMC Microbiology. 2010;193 :1-13 - 80.
Holland IB, Schimdt L, Young J. Type I protein secretion in bacteria, the ABC-transport dependent pathway (review). Molecular Membrane Biology. 2005; 22 :29-39 - 81.
Birosova E, Siegfried L, Kmetova M, et al. Detection and virulence factors in alpha-haemolytic Escherichia coli strains isolated from various clinical materials. CMI. 2004;10 :569-573 - 82.
König B, König W, Scheffer J, Hacker J, Goebel W. Role of Escherichia coli alpha-hemolysin and bacterial adherence in infection: Requirement for release of inflammatory mediators from granulocytes and mast cells. Infection and Immunity. 1986;54 :886-892 - 83.
Scheffer J, König W, Hacker J, Goebel W. Bacterial adherence and hemolysin production from Escherichia coli induces histamine and leukotriene release from various cells. Infection and Immunity. 1985;50 :271-278 - 84.
Czirók E, Milch H, Csiszár K, Csik M. Virulence factors of Escherichia coli . Correlation withEscherichia coli pathogenicity of haemolysin production, haemagglutinating capacity, antigens K1, K5, and colicinogenicity. Acta Microbiologica Hungarica. 1986;33 :69-83 - 85.
Marrs C, Zhang L, Foxman B. Escherichia coli mediated urinary tract infections: Are there distinct uropathogenicE.coli (UPEC) pathotypes? FEMS Microbiology Letters. 2005;252 :183-190 - 86.
Lemonnier M, Landraud L, Lemichez E. Rho GTPase-activating bacterial toxins: From bacterial virulence regulation to eukaryotic cell biology. FEMS Microbiology Review. 2007; 31 :515-534 - 87.
Etienne-Manneville S, Hall A. Rho GTPases in cell biology. Nature. 2002; 420 :629-635 - 88.
Bower JM, Eto DS, Mulvey MA. Covert operations of uropathogenic Escherichia coli within the urinary tract. Traffic. 2005;6 :18-31 - 89.
Yamamoto S, Terai A, Yuri K, Kurazono H, Takeda Y, Yoshida O. Detection of urovirulence factors in Escherichia coli by multiplex polymerase chain reaction. FEMS Immunology & Medical Microbiology. 1995;12 :85-90 - 90.
Rippere-Lampe KE, O’Brien AD, Conrau R, Lockman HA. Mutation of the gene encoding cytotoxic necrotizing factor type 1 (cnf1) attenuates the virulence of uropathogenic Escherichia coli . Infection and Immunity. 2001;69 :3954-3964 - 91.
Elliott SJ, Srinivas S, Albert MJ, et al. Characterization of the roles of hemolysin and other toxins in enteropathy caused by alpha-hemolytic Escherichia coli linked to human diarrhea. Infection and Immunity. 1998;66 :2040-2051 - 92.
Taylor PW. Bactericidal and bacteriolytic activity of serum against gram-negative bacteria. Microbiological Reviews. 1983; 47 :46-83 - 93.
Montenegro MA, Bitter-Suermann D, Timmis JK, et al. traT gene sequences, serum resistance and pathogenicity-related factors in clinical isolates ofEscherichia coli and other gram-negative bacteria. The Journal of General and Applied Microbiology. 1985;131 :1511-1521 - 94.
Timmis KN, Boulnois GJ, Bitter-Suermann D, Cabello FC. Surface components of Escherichia coli that mediate resistance to the bactericidal activities of serum and phagocytes. Current Topics in Microbiology and Immunology. 1985;118 :197-218 - 95.
Goldman RC, Joiner K, Leive L. Serum-resistant mutants of Escherichia coli O111 contain increased lipopolysaccharide, lack an O antigen-containing capsule, and cover more of their lipid A core with O antigen. Journal of Bacteriology. 1984;159 :877-882 - 96.
Domingue GJ, Laucirica R, Baliga P, Covington S, Robledo JA, Li SC. Virulence of wild-type E. coli uroisolates in experimental pyelonephritis. Kidney International. 1998;34 :761-765 - 97.
Iwahi T, Abe Y, Tsuchiya K. Virulence of Escherichia coli in ascending urinary-tract infection in mice. Journal of Medical Microbiology. 1982;15 :303-316 - 98.
Mangel W, Toledo DL, Brown MT, Worzalla K, Lee M, Dunn JJ. Omptin: An Escherichia coli outer membrane proteinase that activates plasminogen. Methods in Enzymology. 1994;244 :384-399 - 99.
Leytus SP, Bowles LK, Konisky K, Mangel WF. Activation of plasminogen to plasmin by a protease associated with outer membrane of Escherichia coli . Proceedings of the National Academy of Sciences of the United States America. 1981;78 :1485-1489 - 100.
Hui CY, Guo Y, He QS, et al. Escherichia coli outer membrane protease OmpT confers resistance to urinary cationic peptides. Microbiology and Immunology. 2010;54 :452-459 - 101.
Lundrigan MD, Webb RM. Prevalence of ompT amongEscherichia coli isolates of human origin. FEMS Microbiology Letters. 1992;76 :51-56 - 102.
McCarter JD, Stephens D, Shoemaker K, Rosenberg S, Kirsch JF, Georgiou G. Substrate specificity of Escherichia coli outer membrane protease ompT. Journal of Bacteriology. 2004;186 :5919-5925 - 103.
Guina T, Yi EC, Wang H, Hackett M, Miller SI. A PhoP-regulated outer membrane protease of Salmonella enterica serovar Typhimurium promotes resistance to alpha-helical antimicrobial peptides. Journal of Bacteriology. 2000;182 :4077-4086 - 104.
Stumpe S, Schmid R, Stephens DL, Georgiou G, Bakker E. Identification of OmpT as the protease that hydrolyzes the antimicrobial peptide protamine before it enters growing cells of Escherichia coli . Journal of Bacteriology. 1998;180 :4002-4006 - 105.
Kanamura S, Kurazono H, Ishitoya S, et al. Distribution and genetic association of putative uropathogenic virulence factors iroN, iha, kpsMT, ompT andusp inEscherichia coli isolated from urinary tract infections in Japan. Journal of Urology. 2003;170 :2490-2493 - 106.
Nakano M, Yamamoto S, Terai A, Ogawa O, Makino S, Hayashi H, Nair GB, Kurazono H. Structural and sequence diversity of the pathogenicity island of uropathogenic Escherichia coli which encodes the USP protein. FEMS. 2001;205 :71-76 - 107.
Rijavec M, Muller-Premru M, Zakotnik B, Zgur-Bertok D. Virulence factors and biofilm production among E. coli strains causing bacteremia of urinary tract origin. Journal of Medical Microbiology. 2008;57 :1329-1334 - 108.
Kanamaru S, Kurazono H, Nakano M, Terai A, Ogawa O, Yamamoto S. Subtyping of uropathogenic Escherichia coli according to the pathogenicity island encoding uropathogenic-specific protein: Comparison with phylogenetic groups. International Journal of Urology. 2006;13 :754-760 - 109.
Yamamoto S. Molecular epidemiology of uropathogenic Escherichia coli . Journal of Infection and Chemotherapy. 2007;13 :68-73 - 110.
Kai-Larsen Y, Luthje P, Chromek M, et al. Uropathogenic Escherichia coli modulates immune responses and its curli fimbriae interact with the antimicrobial peptide LL-37. PLoS Pathogens. 2010;6 :e1001010 - 111.
Luthje P, Brauner A. Ag43 promotes persistence of uropathogenic Escherichia coli isolates in the urinary tract. Journal of Clinical Microbiology. 2010;48 :2316-2317 - 112.
Schroeder M, Brooks BD and Brooks AE. The complex relationship between virulence and antibiotic resistance. Genes (Basel). 2017; 8 :39 - 113.
Kostakioti M, Hadjifrangiskou M, Hultgren SL. Bacterial biofilms: Development, dispersal, and therapeutic strategies in the dawn of the post-antibiotic era. Cold Spring Harbor Perspectives in Medicine. 2013; 3 :a010306 - 114.
De la Fuente-Núñez C, Reffuveille F, Fernández L, Hancock RE. Bacterial biofilm development as a multicellular adaptation: Antibiotic resistance and new therapeutic strategies. Current Opinion in Microbiology. 2013; 16 :580-589 - 115.
Gophna U, Barlev M, Sejffers R, Oelschlager TA, Hacker J, Ron EZ. Curli fibers mediate internalization of Escherichia coli by eukaryotic cells. Infection and Immunity. 2001;69 :2659-2665 - 116.
Bailey JK, Pinyon JL, Ananthan S, Hall RM. Distribution of human commensal Escherichia coli phylogenetic groups. Journal of Clinical Microbiology. 2010;48 :3455-3456 - 117.
Johnson JR, Russo TA. Extraintestinal pathogenic Escherichia coli : “The other badE. coli .” Journal of Clinical Medicine. 2002;139 :155-162 - 118.
Kuntaman K, Lestari ES, Severin JA, Kershof, et al. Fluoroquinolone resistant Escherichia coli , Indonesia. Emerging Infectious Diseases. 2005;11 :1363-1369 - 119.
Takahashi A, Kanamaru S, Kurazono H, Kunishima Y, Tsukamoto T, Ogawa O, Yamamoto S. Escherichia coli isolates associated with uncomplicated and complicated cystitis and asymptomatic bacteriuria possess similar phylogenies, virulence genes, and O-serogroup profiles. Journal of Clinical Medicine. 2006;44 :4589-4592 - 120.
Picard B, Garcia JS, Gouriou S, et al. The link between phylogeny and virulence in Escherichia coli extra-intestinal infection. Infection and Immunity. 1999;67 :546-553 - 121.
Johnson JR, Russo TA. Molecular epidemiology of extra-intestinal pathogenic (uropathogenic) Escherichia coli . A review. The Indian Journal of Medical Microbiology. 2005;295 :383-404 - 122.
Johnson JR, Kuskowski MA, Gajewski A, et al. Extended virulence genotypes and phylogenetic background of Escherichia coli isolates from patients with cystitis, pyelonephritis, or prostatitis. The Journal of Infectious Diseases. 2005;191 :46-50 - 123.
Johnson JR. Microbial virulence determinants and the pathogenesis of urinary tract infection. Infectious Disease Clinics of North America. 2003; 17 :261-278 - 124.
Goluszko P, Moseley SL, Truong LD, et al. Development of experimental model of chronic pyelonephritis with Escherichia coli O75:K5:H-bearing Dr fimbriae: Mutation in thedra region prevented tubulo-interstitial nephritis. Journal of Clinical Investigation. 1997;99 :1662-1672 - 125.
Roberts JA, Marklund B, I Ilver D, et al. The Gal alpha (1-4) Gal-specific tip adhesin of Escherichia coli P-fimbriae is needed for pyelonephritis to occur in the normal urinary tract. Proceedings of the National Academy of Sciences of the United States of America. 1994;91 :11889-11893 - 126.
Kudinha T, Johnson JR, Andrew SD, Kong F, Anderson P, Gilbert GL. Distribution of phylogenetic groups, sequence type ST131, and virulence associated traits among Escherichia coli isolates from men with pyelonephritis or cystitis and healthy controls. Clinical Microbiology and Infection. 2013;19 :E173-E180 - 127.
Piatti G, Mannini A, Balistreri M, Schito AM. Virulence factors in urinary Escherichia coli strains: Phylogenetic background and quinolone and fluoroquinolone resistance. Journal of Clinical Microbiology. 2008;46 :480-487 - 128.
Kudinha T, Johnson JR, Andrew SD, Kong F, Anderson P, Gilbert GL. Genotypic and phenotypic characterization of Escherichia coli isolates from children with urinary tract infection and from healthy carriers. The Pediatric Infectious Disease Journal. 2013;32 :543-548 - 129.
Johnson JR, Delavari P, Kuskowski MA, Stell AL. Phylogenetic distribution of extra-intestinal virulence-associated traits in Escherichia coli . The Journal of Infectious Diseases. 2001;183 :78-88 - 130.
Johnson JR, Stell AL. Extended virulence genotypes of Escherichia coli strains from patients with urosepsis in relation to phylogeny and host compromise. The Journal of Infectious Diseases. 2000;181 :261-272 - 131.
Escobar-Páramo P, Clermont O, Blanc-Potard AB, Bui H, Le Bouguénec C, Denamur E. A specific genetic background is required for acquisition and expression of virulence factors in Escherichia coli . Molecular Biology and Evolution. 2004;21 :1085-1094 - 132.
Dobrindt U, Blum-Oehler G, Hartsch T, et al. S-fimbria-encoding determinant sfa1 is located on pathogenicity island III536 of uropathogenicEscherichia coli strain 536. Infection and Immunity. 2001;69 :4248-4256 - 133.
Guyer DM, Kao J-S, Mobley HLT. Genomic analysis of a pathogenicity island in uropathogenic Escherichia coli CFT 073: Distribution of homologous sequences among isolates from patients with pyelonephritis, cystitis, and catheter-associated bacteriuria and from fecal samples. Infection and Immunity. 1998;66 :4411-4417 - 134.
Hacker J, Kaper JB. Pathogenicity islands and the evolution of microbes. Annual Review of Microbiology. 2000; 54 :641-679 - 135.
Barber AE, Norton JP, Spivak AM, and Mulvey MA. Urinary tract infections: Current and emerging management strategies. Clinical Infectious Diseases. 2013; 57 :719-724 - 136.
Goettsch W, van Pelt W, Nagelkerke N, et al. Increasing resistance of fluoroquinolones in Escherichia coli from urinary tract infections in The Netherlands. Journal of Antimicrobial Chemotherapy. 2000;46 :223-228 - 137.
Gupta K, Hooton TM, Stamm WE. Increasing antimicrobial resistance and the management of uncomplicated community-acquired urinary tract infection. Annals of Internal Medicine. 2001; 135 :41-50 - 138.
Karlowsky JA, Hoban DJ, DeCorby MR, Liang NM, Zhanel GG. Fluoroquinolone resistant urinary isolates of Escherichia coli from outpatients are frequently multidrug resistant: Results from the North American Urinary Tract Infection Collaborative Alliance-Quinolone Resistance Study. Antimicrobial Agents and Chemotherapy. 2006;50 :2251-2254 - 139.
Wong-Beringer A, Hindler J, Loeff M, et al. Molecular correlation for the treatment outcomes in bloodstream infections caused by Escherichia coli andKlebsiella pneumoniae with reduced susceptibility to ceftazidime. Clinical Infectious Diseases. 2002;34 :135-146 - 140.
Foxman B. Epidemiology of urinary tract infections: Incidence, morbidity, and economic costs. American Journal of Medicine. 2002; 113 :5S-13S - 141.
Drews SJ, Poutanen SM, Mazzulli T, et al. Decreased prevalence of virulence factors among ciprofloxacillin-resistant uropathogenic Escherichia coli isolates. Journal of Clinical Microbiology. 2005;43 :4218-4220 - 142.
Vila J, Simon K, Ruiz J, et al. Are quinolone-resistant uropathogenic Escherichia coli less virulent? Journal of Infectious Diseases. 2002;186 :1039-1042 - 143.
Velasco M, Horcajada JP, Mensa J, et al. Decreased invasive capacity of quinolone-resistant Escherichia coli in patients with urinary tract infections. Clinical Infectious Diseases. 2001;33 :1682-1686 - 144.
Johnson JR, Van der Sche C, Kuskowski MA, Goessens W, Van Belkum A. Phylogenetic background and virulence profiles of fluoroquinolone-resistant clinical Escherichia coli isolates from the Netherlands. Journal of Infectious Diseases. 2002;186 :1852-1856 - 145.
Platell JL, Cobbold RN, Johnson JR, et al. Commonality among fluoroquinolone-resistant sequence type ST131 extra-intestinal Escherichia coli isolates from humans and companion animals in Australia. Antimicrobial Agents and Chemotherapy. 2011;55 :3782-3787 - 146.
Platell JL, Johnson JR, Cobbold RN, Trott DJ. Multidrug-resistant extra-intestinal Escherichia coli of sequence type ST131 in animals and foods. Veterinary Microbiology. 2011;153 :99-108 - 147.
Rogers BA, Sidjabat HE, Paterson DL. Escherichia coli O25b-ST131: A pandemic, multi-resistant, community-associated strain. Journal of Antimicrobial Chemotherapy. 2011;66 :1-14 - 148.
Johnson JR, Menard M, Johnston B, Kuskowski MA, Nichol K, Zhanel GG. Epidemic clonal groups of Escherichia coli as a cause of antimicrobial resistant urinary tract infections in Canada, 2002-2004. Journal of Antimicrobial Chemotherapy. 2009;53 :2733-2739 - 149.
Cheng MF, Chen WL, Hung WY, et al. Emergence of extended spectrum-β-lactamase-producing Escherichia coli O25b-ST131: A major community-acquired uropathogen in infants. The Pediatric Infectious Disease. 2015;4 :469-475 - 150.
Lavigne J-P, Vergunst A, Goret L. Virulence potential and genomic mapping of the worldwide clone Escherichia coli ST131. PLoS One. 2012;7 :e34294 - 151.
Matsamura Y, Yamamoto M, Nagao M, Hotta H, et al. Emergence and spread of B2-ST131-O25b, B2-ST131-O16 and D-ST405 clonal groups among extended-spectrum-β-lactamase-producing Escherichia coli in Japan. Journal of Antimicrobial Chemotherapy. 2012;67 :2612-2620 - 152.
Kudinha T, Johnson JR, Andrew SD, Kong F, Anderson P, Gilbert GL. Escherichia coli sequence type 131 (ST131) as a prominent cause of antimicrobial resistance among clinical and fecalEscherichia coli isolates from reproductive-age women. Journal of Clinical Microbiology. 2013;51 :3270-3276 - 153.
Zhong YM, Liu WE, Liang XH, Li YM, Jian ZJ, Hawkey PM. Emergence and spread of O16-ST131 and O25b-ST131 clones among faecal CTX-M-producing Escherichia coli in healthy individuals in Hunan Province, China. Journal of Antimicrobial Chemotherapy. 2015;70 :2223-2227 - 154.
Johnson JR, Johnston B, Clabots C, Kuskowski MA, Castanheira M. Escherichia coli sequence type ST131 as the major cause of serious multidrug-resistantE. coli infections in the United States. Clinical Infectious Diseases. 2010;51 :286-294 - 155.
Cerquetti M, Giufre M, Garcia-Fernandez A, et al. Ciprofloxacin-resistant, CTX-M-15 producing Escherichia coli ST131 clone in extraintestinal infections in Italy. Clinical Microbiology and Infection. 2010;16 :1555-1558 - 156.
Uchida Y, Mochiman T, Morokuma Y, et al. Clonal spread in Eastern Asia of ciprofloxacin-resistant Escherichia coli serogroup O25 strains, and associated virulence factors. International Journal of Antimicrobial Agents. 2010;35 :444-450 - 157.
Zong Z, Partridge SR, Thomas L, Iredell JR. Dominance of blaCTX-M within an Australian extended-spectrum beta-lactamase gene pool. Antimicrobial Agents and Chemotherapy. 2008;52 :4198-4202