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Medicine » Infectious Diseases » "Clinical Management of Complicated Urinary Tract Infection", book edited by Ahmad Nikibakhsh, ISBN 978-953-307-393-4, Published: September 6, 2011 under CC BY-NC-SA 3.0 license. © The Author(s).

Chapter 10

Biofilm Formation in Uropathogenic Escherichia coli Strains: Relationship with Urovirulence Factors and Antimicrobial Resistance

By Sara M. Soto, Francesc Marco, Elisabet Guiral and Jordi Vila
DOI: 10.5772/24626

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Biofilm Formation in Uropathogenic Escherichia coli Strains: Relationship with Urovirulence Factors and Antimicrobial Resistance

Sara M Soto1, Marco Francesc1, Elisabet Guiral1 and Jordi Vila1

1. Introduction

1.1. Escherichia coli virulence and urinary tract infections

Urinary tract infections are a major public health concern in developed countries and also represent one of the most common hospital-acquired infections. Most uncomplicated UTIs are caused by E. coli, accounting for up to 90% of community-acquired and approximately 50% of nosocomial UTIs (Vila et al., 2002). The origin of these strains is frequently the patient’s own intestinal flora. In comparison to commensal strains, UPEC present several virulence factors that allow them to colonize host mucosal uro-epithelium, injure and invade host tissues, overcome host defence mechanisms, incite a host inflammatory response and eventually proceed from the lower urinary tract to the renal cavities and tissues. The virulence factors involved in UTIs include surface virulence factors such as type 1 fimbriae, P, S and F1C fimbriae; exported virulence factors such as α-haemolysin, cytotoxic necrotising factor 1 (CNF1), secreted autotransporter toxin (SAT), cytolethal distending toxin (CDT) and cytolysin A (Caprioli et al., 1987; Lai et al., 2000; Smith et al., 1963; Tóth et al., 2000).

A common problem in UTI is recurrence, even in patients without anatomic abnormalities or indwelling bladder catheters. It is estimated that 40 to 50% of adult healthy women have experienced at least one UTI in their lifetime, and there is a tendency for these infections to become chronic due to a high rate of recurrence (Ulett et al., 2007). The persistence of the same E. coli strain in the urinary tract may be the cause of recurrent prostatitis. In fact, it has been shown that after an episode of acute prostatitis, cultures of expressed prostatic secretions are still positive three months after the end of a six-week course of therapy in one third of men (Kravchick et al., 2004). This may be related to the capacity of bacteria to form biofilm structures. Biofilm can promote persistence in the urinary tract and on biomaterial surfaces by protecting bacteria from the clearing out effect of hydrodynamic forces and the killing activity of host defence mechanisms and antibiotics (Hanna et al., 2003).

1.2. Biofilm and factors involved in its formation

Biofilm is defined as a structured community of bacterial cells enclosed in a self-produced polymeric matrix and adherent to an inert or living surface (Costerton et al., 1999). Biofilm formation is carried out in four steps: adhesion or attachment, early development of biofilm structure, maturation and dispersion of cells from the biofilm into the surrounding environment and return to the planktonic state.

Several surface determinants are involved in biofilm formation such as:

1.2.1. Flagella and motility

Motile E. coli generally present multiple peritrichous flagella. Motility is involved in colonization of host organisms or target organs and promotes initial cell-to-surface contact.

1.2.2. Fimbriae

Fimbriae are one of the virulent factors associated with host tissue adhesion of pathogenic E. coli strains (Finlay et al., 1997). Among these, type 1 fimbriae are the most common among E. coli and have an important role in the initial attachment to abiotic surface in biofilm formation (Pratt et al., 1998).

1.2.3. Autotransporter proteins

These secretory proteins present all the requirements for secretion across the cytoplasmic and the outer membrane to the bacterial cell surface (Desvaux et al., 2004). Among these proteins Ag43, AIDA (adhesin involved in diffuse adherence) and TibA are involved in adhesion. Antigen 43 promotes aggregation of cells through Ag43-Ag43 interactions by an intercellular handshake mechanism (Hasman et al., 1999). Ag43 and type 1 fimbriae are expressed co-ordinately in the cells which normally produce only one type of adherence structure at a time (Schembri et al., 2001). AIDA and TibA are autotransporters with homology to Ag43.

1.2.4. Curli

Curli fimbriae aggregate at the cell surface to form 6- to 12-nm-diameter structures whose length varies between 0.5 and 1 μm. Curli adhesive fibres also promote biofilm formation to abiotic surfaces both by facilitating initial cell–surface interactions and subsequent cell–cell interactions (Cookson et al., 2002; Uhlich et al., 2006; Vidal et al., 1998).

1.2.5. F conjugative pilus

The F-pilus promotes both initial adhesion and biofilm maturation through nonspecific attachment to abiotic surfaces and subsequent cell-to-cell contacts which stabilize the structure of the biofilm (Ghigo et al., 2001; Molin & Tolker-Nielsen, 2003; Reisner et al., 2003).

1.2.6. Exopolysaccharide production

The biofilm matrix is composed by exopolysaccharide. This matrix forms a hydrated viscous layer which protects embedded bacteria from desiccation and from host defences because bacteria forming this structure may not be recognised by the immune system. The matrix may also be involved in the protection of the bacteria against toxic molecules such as antimicrobials, hydroxyl radicals, and superoxide anions). The biofilm matrix could also inhibit wash-out of enzymes, nutrients, or even signalling molecules that could then accumulate locally and create more favourable microenvironments within the biofilm (Redfield et al., 2002; Starkey et al., 2004; Welch et al., 2002). All these aspects of the matrix could contribute to development of phenotypic resistance of pathogenic E. coli biofilms and lead to persistent infections (Anderson et al. 2003; Justice et al. 2004). In addition, the exopolysaccharide interactions with other components of the matrix favour the three-dimensional growth of the biofilm (White et al., 2003). The exopolysaccharides most frequently found in the matrix are poly-β-1,6-N-acetyl-glucosamine, cellulose, colanic acid, lipopolysaccharides and capsules.

In this chapter, the role of biofilm in urinary tract infections and its relation with virulence factors and antimicrobial resistance is explained.

2. Evolution of antimicrobial resistance in uropathogenic Escherichia coli (UPEC)

Several studies have demonstrated an increase in antibiotic resistance levels in E. coli causing community-acquired urinary tract infection (UTI) (Barret et al., 1999; Daza et al., 2001; Goettsch et al., 2000; Goldstein, 2000; Gupta et al., 2001a). Some authors have suggested that most of these studies are likely to reflect a selection bias because few UTIs are being cultured routinely and culture results are available from patients with complications, recent treatment, and recurrence of infection or suspected resistance (Gupta et al., 2001b). However, taking into account the worldwide increase in antibiotic resistance, this factor can be a major problem in complicated and uncomplicated community-acquired UTIs. Hence, as suggested by the Infectious Diseases Society of America (IDSA), knowledge of local resistance rates and surveillance studies to monitor changes in the susceptibility of E. coli is highly recommended. (Warren et al., 1999)

Cotrimoxazole has been the drug of choice for empiric therapy of uncomplicated UTI in women during several years. However, resistance to this compound is higher than 20% in many countries. In Spain, a multicentre study performed in 2006 found a resistance level of 32%, (Andreu et al., 2008) quite similar to the result of 33.9 %found in a previous study completed four years beforehand (Andreu et al., 2005), making the differences found between regions noteworthy (range 23% to 37.3%). Results from a single centre also in Spain found a resistance rate of 25%, with isolates from complicated UTIs (28%) being more resistant than those than from uncomplicated UTIs (22%) (Alós et al., 2005). In the USA, resistance to cotrimoxazole has risen from 15% in 1998 to 21.3% in 2003-2004 (Gupta et al., 2001b)). Again, geographic variations were observed in another study among states (15% to 40%) in the USA and in Canada (10.2 to 48.5%) (Zhanel et al., 2006).

Betalactam antibiotics are widely used in the treatment of UTIs. Among them, ampicillin or amoxicillin are not recommended as first line drugs due to high levels of resistance. In the multicentre study from Spain (Andreu et al., 2008) the rate of resistance was 60.7% with clear differences between regions, the lowest value being 36.8%. Despite ampicillin not having been used to treat uncomplicated cystitis for a long time, resistance to this compound has increased along the years. Amoxicillin plus clavulanic acid shows a high level of activity compared to ampicillin. Resistance to this drug was only found in 8.1% of isolates with a variation according to geographic zones of 3% to 18.3% (Andreu et al., 2008). Other oral betalactams like cefuroxime (8.9% of resistance) or cefixime (6.9% of resistance) show good activity against E. coli urinary isolates, but resistance to both drugs was higher in elderly patients (>60 years)(Andreu et al., 2008). An E. coli producer of extended spectrum betalactamases should always be considered as an aetiological agent of UTIs. In the Spanish multicentre study (Andreu et al., 2008) this agent represented 5.2% of E. coli isolates with most (79.1%) being recovered from patients over the age of 60 years. These isolates are also frequently resistant to fluorquinolones and cotrimoxazole.

Fluorquinolones can be an option to treat UTIs, but their utility is hampered by resistance rates. In Europe, resistance to ciprofloxacin in UPEC was low in the period from 1999-2000, with the highest values found in Portugal (5.8%) and Spain (14.7%) (Kahlmeter, 2003). The multicentre study published by Zhanel et al. (2006) reported a rate resistance in UPEC of only 1.1% in Canada and 6.8% in the USA, with great differences between regions (2.9% to 20.3%). In the Spanish multicentre study (Andreu et al., 2008) resistance to ciprofloxacin was found in 23.9% of all UPEC isolates and, again, significant geographical differences were found (12.5% to 37.3%). Interestingly, the study by Alós et al., (2005) showed that resistance to ciprofloxacin was higher in UPEC recovered in complicated UTIs (19.5%) than in UPEC isolated in uncomplicated UTIs (8.5%). Both studies found that elderly patients showed higher levels of resistance to fluorquinolones.

Nitrofurantoin shows a good activity against UPEC isolates with only 3.8% resistant isolates (Andreu et al., 2008). However, dosage and potential pulmonary toxicity limits their usefulness. Fosfomycin remains as the most active oral antibiotic against UPEC isolates. Resistance to this drug was of 1.7% in the multicentre study published by Andreu et al., (2008) and the compound usually maintains its activity against ESBL producers.

3. Relationship between virulence factors and antimicrobial resistance in UPEC

The level of quinolone-resistance in E. coli clinical isolates has steadily increased in most European countries. When the analysis is stratified according to the different UTIs it is found that the percentage of quinolone-resistant E. coli isolates causing pyelonephritis is lower that those causing cystitis (Velasco et al., 2001). This data suggested that the quinolone-resistant E. coli lost the ability to colonize the kidney epithelia. In order, to prove this hypothesis a study investigating some urovirulence factors in nalidixic acid resistant E. coli clinical isolates compared with a group of quinolone-susceptible clinical isolates was carried out. Haemolysin, cytotoxic necrotizing factor-1 (CNF-1) and the autotransporter toxin (sat) were less prevalent in nalidixic acid-resistant than in nalidixic acid susceptible strains. These results suggested that resistance to quinolones may be associated with a decrease in the presence of some virulence factors in uropathogenic E. coli (Vila et al., 2002). A study related quinolone resistance and low virulence with phylogenetic origin, mainly in phylogenetic group A, which show a high level of resistance to quinolones and has a low number of urovirulence factors (Johnson JR, et al., 2003). Among the four phylogenetic groups (A, B1, B2 and D), B2 is considered the most virulent. Therefore in a subsequent study, 31 virulence factors were analyzed among nalidixic acid-susceptible and –resistant E. coli clinical isolates from phylogenetic group B2 and again haemolysin and CNF-1 were less prevalent among nalidixic acid-resistant E. coli strains (Horcajada JP, et al. 2005). All three genes (hly, encoding haemolysin; cnf, encoding the cytotoxic necrotizing factor and sat, encoding the autotransporter toxin) have their localization in pathogenicity islands in common. Therefore, we thought that the link between the acquisition of resistance to quinolone and lower prevalence of some virulence factors could be explained by the fact that quinolones have been shown to induce the SOS system (Phillips I. et al., 1987) and this induction can favour the release of a genome phage integrated in the bacterial chromosome. Since the structure of the genome phage and the pathogenicity islands is genetically similar it can be hypothesized that the induction of the SOS system by quinolones would favour the release and loss of the pathogenicity island. Indeed, this hypothesis was proven incubating haemolysin-positive, quinolone-susceptible E. coli strains with subinhibitory concentrations of ciprofloxacin and searching for haemolysin-negative E. coli mutants. It was shown that these mutants can suffer a partial or total loss of the pathogenicity island, carrying the hly and cnf genes through a dependent and independent SOS pathway, respectively (Soto et al., 2006). All the abovementioned results suggest that the acquisition of quinolone resistance may generate E. coli strains with lower virulence.

4. Relationship between biofilm formation, urovirulence factors and antimicrobial resistance

Biofilm formation may be considered as another pathogenic determinant which allows the strains to persist a long time in the genito-urinary tract and interfere with bacterial eradication. Biofilm endows bacteria with several advantages, such as the acquisition of antibiotic tolerance, expression of several virulence factors and an increased resistance against phagocytosis and other host defence mechanisms. Actually, biofilms are probably the usual living condition of bacteria in natural environments and they are, indeed, regularly involved in infections associated with biomaterials such as catheters or prostheses. In these clinical processes, biofilm formation is the main culprit of the characteristic persistence of the infection, despite appropriate antibiotic therapy and hydrodynamic forces (Hanna et al., 2003). More than 50% of all bacteria infections reported involve biofilm formation (Costerton et al., 1999).

Acute UTI caused by UPEC can lead to recurrent infection, which is denominated “relapse” when it is caused by the same strain as that involved in the original UTI or as “re-infection” when it involves different strains. Approximately 25% of women with an episode of acute cystitis later develop recurrent UTI being an important burden to the health system. A study of women with recurrent UTI showed that 74% of strains causing relapse were biofilm formers (Soto et al., 2007). It had been demonstrated that uropathogens can persist within the bladder tissue in underlying epithelial cells or creating pod-like bulges on the bladder surface being a source of recurrent UTI (Mulvey et al., 2000; Anderson et al., 2003). Two virulence factors related to iron-uptake system, yersiniabactin and aerobactin, have also been associated with relapse (Johnson et al., 2001; Soto et al., 2006) due to the need of the bacteria to capture iron for growth in a stressful environment such as the vagina. However, biofilm production may be the key determinant for the persistence of UPEC in the vaginal reservoir, the bladder epithelial cells or both.

The study of the factors contributing to biofilm formation may be important to conceive new therapeutic solutions for the treatment of these infections. On comparing UPEC collected from patients with cystitis, pyelonephritis or prostatitis it had been observed that strains causing prostatitis presented a higher capacity to form “in vitro” biofilm than those causing cystitis and pyelonephritis (Soto et al., 2007). The increased capacity to form biofilm of these strains could be a possible explanation for the persistence of such strains in the prostatic secretory system.

Wu and colleagues (Wu et al., 1996) suggested that the inhibition of bacterial attachment to an uroepithelial surface, a crucial initial event involving precise interactions between groups of bacterial adhesive molecules called adhesins and their cognate urinary tract receptors, could be interesting to avoid biofilm formation. One of the virulence factors involved in the initial steps of biofilm is type 1 fimbriae which play an important role in the adhesion to the host epithelial cells (Prüss et al., 2006) and confer binding to α-D-mannosylated proteins, such as uroplakins, which are abundant in the bladder (Wu et al., 1996). It had been found that biofilm-producing E. coli strains showed a significantly greater type 1 fimbriae expression than non-biofilm producing strains (Soto et al., 2007).

Another mechanism by which UPEC promotes the formation of biofilms is via expression of proteins that mediate cell-cell aggregation (Ulett et al., 2007). Of these, Ag43 is also associated with the early stages of biofilm development (Schembri et al., 2003), although it has been demonstrated that the Ag43 can be dispensable for biofilm formation being replaced by alternative factors, such as conjugative pili (Guigo et al., 2001; Reisner et al., 2003). Ag43 is expressed on the surface of UPEC cells located within intracellular biofilm-like bacterial pods in the bladder epithelium, indicating that it may contribute to survival and persistence during prolonged infection (Anderson et al., 2003).

On the other hand, among of the virulence factors studied, only haemolysin seems to present an association with biofilm production. In fact, haemolysin-positive UPEC strains were strongly linked to prostatitis also shown to have a higher frequency of “in vitro” biofilm formation (Andreu et al., 1997; Johnson et al., 2005; Mitsumori et al., 1999; Ruiz et al., 2002; Soto et al., 2007; Terai et al., 1997). These data confirm that the tropism and invasiveness of E. coli strains for the prostate rely mainly on haemolysin but also provide a possible explanation for the persistence of such strains in the prostatic secretory system by means of their increased ability to form biofilm.

It has been previously reported that most E. coli isolates collected from faeces belong to phylogenetic groups A and B1, with phylogenetic groups B2 and D being the most frequently isolated in urine and considered as virulent. The differences in the phylogenetic background of these two groups of isolates from urine and faeces indicate that the prostate was not, in most of the cases, colonized by commensal bacteria from the intestinal tract. Strains belonging to phylogenetic group B2 presented a higher capacity to form biofilm than those belonging to phylogenetic groups A, B1 and D (Soto et al., 2007).

A relationship between nalidixic acid susceptibility and “in vitro” biofilm formation seems to exist. Studies comparing biofilm positive UPEC strains versus biofilm negative UPEC strains showed that the percentage of nalidixic acid resistant strains was higher among those non-biofilm formers than among biofilm-formers (Soto et al., 2007). In fact, acquisition of quinolone resistance causes a decrease in the “in vitro” production of biofilm by a decrease in the expression of type 1 fimbriae, avoiding the first step of biofilm formation, the adhesion to the surfaces (unpublished data).

5. Conclusion

Biofilm formation is an important feature related to relapsed UTI, and likely plays an important role in prostatitis caused by E. coli. In addition, a link between acquisition of quinolone resistance acquisition and decrease in biofilm formation and loss of some virulence factors has been suggested.


This work was supported by the Spanish Network for Research in Infectious Diseases (REIPI RE06/0008), SGR091256 of the Department d’Universitats, Recerca I Societat de la Informació de la Generalitat de Catalunya, Fondo de Investigaciones Sanitarias (PI10/01579) of Spain, and by funding from the European Community (TROCAR contract HEALTH-F3-2008-223031). Sara M. Soto is a recipient of a contract “Miguel Servet” (CP05/00140) from “Fondo de Investigaciones Sanitarias” of the Spanish Ministry of Health.


1 - I. Alós, M. G. Serrano, Garcés. J. L. Gómez, J. Perianes, 2005Antibiotic resistance of Escherichia coli from community-acquired urinary tract infections in relation to demographic and clinical data. Clinical Microbiology and Infection 11 3 199 203 0119-8743X.
2 - G. G. Anderson, J. J. Palermo, J. D. Schilling, R. Roth, J. Heuser, S. J. Hultgren, 2003 Intracellular bacterial biofilm-like pods in urinary tract infections. Science, 301 5629 105 107 1095-9203
3 - Andreu, A.; Stapleton, A.E.; Fennel, C.; Lockman, H.A.; Xercavins, M.; Fernandez,F.; Stamm, W.E. (1997). Urovirulence determinants in Escherichia coli strains causing prostatitis. Journal of Infectious Diseases, 0022-1899 2 176 464
4 - A. Andreu, I. Alós, M. Gobernado, F. Marco, M. de la Rosa, J. A. García-Rodríguez, 2005Etiology and antimicrobial susceptibility among uropathogens causing community-acquired lower urinary tract infections: a nationwide surveillance study. Enfermedades Infecciosas y Microbiol ogia Clinica, 23 1 4 9 0021-3005X.
5 - A. Andreu, I. Planells, 2008Grupo cooperativo Español para el estudio de la sensibilidad antimicrobiana a los patógenos urinarios.. Etiology of community-acquired lower urinary infections and antimicrobial resistance of Escherichia coli: a national surveillance study. Medicina Clinica (Barcelona). 130 13 481 486 0025-7753
6 - S. P. Barrett, M. A. Savage, M. P. Rebec, A. Guyot, N. Andrews, S. B. Shrimpton, 1999 Antibiotic sensitivity of bacteria associated with community-acquired urinary tract infection in Britain. Journal of Antimicrobial Chemotherapy, 44 3 359 365 0305-7453
7 - A. Caprioli, V. Falbo, F. M. Ruggeri, L. Baldassarri, R. Bisicchia, G. Ippolito, E. Romoli, G. Donelli, 1987 Cytotoxic necrotizing factor production by hemolytic strains of Escherichia coli causing extraintestinal infections. Journal of Clinical Microbiology, 25 1 146 149 0095-1137
8 - A. L. Cookson, W. A. Cooley, M. J. Woodward, 2002 The role of type 1 and curli fimbriae of Shiga toxin-producing Escherichia coli in adherence to abiotic surfaces International Journal of Medical Microbiology 292 3-4 195 205 1438-4221
9 - J. W. Costerton, Z. Lewandowski, D. E. Caldurell, D. R. Korber, H. M. Lappin-Scott, 1995 Microbial biofilms Annual Reviews in Microbiology, 49 711 745 0066-4227
10 - J. W. Costerton, 1999a Introduction to biofilm. International Journal of Antimicrobial Agents 11 3-4 217 221 0924-8579
11 - J. W. Costerton, P. S. Stewart, E. P. Greenberg, 1999b Bacterial biofilms: a common cause of persistent infections Science, 284 5418 1318 1322 1095-9203
12 - R. Daza, J. Gutierrez, G. Piedrola, 2001 Antibiotic susceptibility of bacterial strains isolated from patients with community-acquired urinary tract infections. International Journal of Antimicrobial Agents 18 3 211 215 0924-8579
13 - M. Desvaux, N. J. Parham, et al. 2004 The autotransporter secretion system. Research in Microbiology 155 2 53 60 0923-2508
14 - B. B. Finlay, 1997 Interactions of enteric pathogens with human epithelial cells. Bacterial exploitation of host processes. Advances in Experimental and Medical Biology, 412 289 293 0065-2598
15 - J. M. Ghigo, 2001 Natural conjugative plasmids induce bacterial biofilm development. Nature 412 6845 442 445 0028-0836
16 - W. Goettsch, W. van Pelt, N. Nagelkerke, M. G. Hendrix, A. G. Buiting, et al. 2000 Increasing resistance to fluoroquinolones in Escherichia coli from urinary tract infections in the Netherlands. Journal of Antimicrobial Chemotherapy, 46 2 223 228 0305-7453
17 - F. W. Goldstein, 2000 Antibiotic susceptibility of bacterial strains isolated from patients with community-acquired urinary tract infections in France. Multicentre Study Group. European Journal of Clinical Microbiololy and Infectious Diseases, 19 2 112 117 0934-9723
18 - K. Gupta, T. M. Hooton, W. E. Stamm, 2001a Increasing antimicrobial resistance and the management of uncomplicated community-acquired urinary tract infections. Annual of International Medicine, 135 1 41 50 0003-4819
19 - K. Gupta, D. F. Sahm, D. Mayfield, W. E. Stamm, 2001b Antimicrobial resistance among uropathogens that cause community-acquired urinary tract infections in women: a nationwide analysis Clinical Infectious Diseases 33 1 89 94 1058-4838
20 - Hanna, A.; Berg, M.; Stout, V.; Razatos, A. (2003). Role of capsular colanic acid in adhesion of uropathogenic Escherichia coli. Applied Environmental Microbiology, 0099-2240 8 69 4474 4481
21 - H. Hasman, T. Chakraborty, P. Klemm, 1999 Antigen-43-mediated autoaggregation of Escherichia coli is blocked by fimbriation. Journal of Bacteriology 181 16 4834 4841 0021-9193
22 - J. P. Horcajada, S. M. Soto, A. Gajewski, Anta. M. T. Jiménez de, J. Mensa, J. Vila, J. R. Johnson, 2005Quinolone resistant uropathogenic Escherichia coli from phylogeneticgroup B2 have fewer virulence factors than their susceptible counterparts. Journal of Clinical Microbiology, 43 6 2962 2964 0095-1137
23 - Johnson, J.R.; O’Bryan, T.T.; Delavari, P.; Kuskowski, M.; Stapleton, A.; Carlino, U.; et al. (2001). Clonal relationships and extended virulence genotypes among Escherichia coli isolates from women with a first or recurrent episode of cystitis. Journal of Infectious Diseases, 0022-1899 183 1508 1517
24 - Johnson, J.R.; Kuskowski, M.A.; Owens, K.; Gajewski, A.; Winokur, P.L. (2003). Phylogenetic origin and virulence genotype in relation to resistance to fluoroquinolones and/or extended-spectrum cephalosporins and cephamycins among Escherichia coli isolates from animals and humans. Journal of Infectious Diseases, 0022-1899 5 188 759 768
25 - Johnson, J.R.; Kuskowski, M.A.; Gajewski, A.; Soto, S.; Horcajada, J.P.; Jimenez de Anta, M.T.; Vila, J. (2005). Extended virulence genotypes and phylogenetic background of Escherichia coli isolates from patients with cystitis, pyelonephritis, or prostatitis. Journal of Infectious Diseases 0022-1899 1 191 46 50
26 - S. S. Justice, C. Hung, J. A. Theriot, D. A. Fletcher, G. G. Anderson, M. J. Footer, et al. 2004 Differentiation and developmental pathways of uropathogenic Escherichia coli in urinary tract pathogenesis Procedings of the National Academy of Sciences of the United States of America, 101 5 1333 1338 0027-8424
27 - G. Kahlmeter, 2003 An international survey of the antimicrobial susceptibility of pathogens from uncomplicated urinary tract infections: the ECO-SENS ProjectInternational Journal of Antimicrobial Agents, 22 1 S49 S52 0924-8579
28 - S. Kravchick, S. Cytron, L. Agulansky, D. Ben-Dor, 2004 Acute prostatitis in middle-aged men: a prospective studyBritish Journal of Urology International, 93 1 93 96 0146-4410X.
29 - X. H. Lai, I. Arencibia, A. Johansson, S. N. Wai, J. Oscarsson, 2000 Cytocidal and apoptotic effects of the ClyA protein from Escherichia coli on primary and cultured monocytes and macrophagesInfection and Immunity, 68 7 4363 4367 0019-9567
30 - Mitsumori, K.; Terai, A.; Yamamoto, S.; Ishitoya, S.; Yoshida, O. (1999). Virulence characteristics of Escherichia coli in acute bacterial prostatitis. Journal of Infectious Diseases, 0022-1899 4 180 1378 1381
31 - S. Molin, T. Tolker-Nielsen, 2003 Gene transfer occurs with enhanced efficiency in biofilms and induces enhanced stabilisation of the biofilm structure. Current Opinion on Biotechnology, 14 3 255 261 0958-1669
32 - M. A. Mulvey, J. D. Schilling, J. J. Martinez, S. J. Hultgren, 2000 Bad bugs and beleaguered bladders: interplay between uropathogenic Escherichia coli and innate host defenses Procedings of the National Academy of Sciences of the United States of America, 97 16 8829 8835 0027-8424
33 - I. Phillips, E. Culebras, F. Moreno, F. Baquero, 1987 Induction of the SOS response by new 4-quinolones. Journal of Antimicrobial Chemotherapy, 20 5 631 638 0305-7453
34 - L. A. Pratt, R. Kolter, 1998 Genetic analysis of Escherichia coli biofilm formation: roles of flagella, motility, chemotaxis and type I pili. Molecular Microbiology 30 2 285 293 0095-0382X.
35 - B. M. Prüss, C. Besemann, A. Denton, A. J. Wolfe, 2006 A complex transcription network controls the early stages of biofilm development by Escherichia coli. Journal of Bacteriology 188 11 3731 3739 0021-9193
36 - R. J. Redfield, 2002Is quorum sensing a side effect of diffusion sensing? Trends in Microbiology, 10 8 365 370 0096-6842X.
37 - A. Reisner, J. A. Haagensen, M. A. Schembri, E. L. Zechner, S. Molin, 2003 Development and maturation of Escherichia coli K-12 biofilms Molecular Microbiology 48 4 933 946 0095-0382X.
38 - J. Ruiz, K. Simon, J. P. Horcajada, M. Velasco, M. Barranco, G. Roig, A. Moreno-Martinez, J. A. Martinez, Anta. M. T. Jimenez de, J. Mensa, J. Vila, 2002 Differences in virulence factors among clinical isolates of Escherichia coli causing cystitis and pyelonephritis in women and prostatitis in men. Journal of Clinical Microbiology 40 12 4445 4449 0095-1137
39 - M. A. Schembri, G. Christiansen, P. Klemm, 2001 FimH-mediated autoaggregation of Escherichia coli. Molecular Microbiology 41 6 1419 1430 0095-0382X.
40 - Schembri, M.A.; Hjerrild, L.; Gjermansen, M.; Klemm, P. (2003). Differential expression of the Escherichia coli autoaggregation factor antigen 43. Journal of Bacteriology, 0021-9193 7 185 2236 2242
41 - H. W. Smith, 1963 The haemolysins of Escherichia coli. Journal of Pathology and Bacteriology, 85 197 211 0368-3494
42 - S. M. Soto, A. Smithson, J. P. Horcajada, J. A. Martinez, J. Mensa, J. Vila, 2006Implication of biofilm formation in the persistence of urinary tract infection caused by uropathogenic Escherichia coli. Clinical Microbiology and Infection 12 10p.p. 1034 EOF 1036 EOF 0119-8743X.
43 - S. M. Soto, Anta. M. T. Jimenez de, J. Vila, 2006Quinolones induce partial or total loss of pathogenicity islands in uropathogenic Escherichia coli by SOS-dependent or-independent pathways, respectively. Antimicrobial Agents and Chemotherapy, 50 2 649 653 0066-4804
44 - S. M. Soto, A. Smithson, J. A. Martinez, J. P. Horcajada, J. Mensa, J. Vila, 2007 Biofilm formation in uropathogenic Escherichia coli strains: relationship with prostatitis, urovirulence factors and antimicrobial resistance Journal of Urology, 177 1 365 368 0022-5347
45 - A. Terai, S. Yamamoto, K. Mitsumori, Y. Okada, H. Kurazono, Y. Takeda, et al. 1997 Escherichia coli virulence factors and serotypes in acute bacterial prostatitis. International Journal of Urology, 4 3 289 294 0919-8172
46 - I. Toth, E. Oswald, K. Mitsumori, B. Szabo, I. Barcs, L. Emody, 2000 Virulence markers of human uropathogenic Escherichia coli strains isolated in Hungary. Advances in Experimental and Medical Biology, 485 335 338 0065-2598
47 - Uhlich, G. A.; Cooke, P.H.; Solomon, E.B. (2006). Analyses of the red-dry-rough phenotype of an Escherichia coli O157:H7 strain and its role in biofilm formation and resistance to antibacterial agents. Applied Environmental Microbiology, 0099-2240 4 72 2564 2572
48 - Ulett, G. C.; Mabbett,A.N.; Fung, K.C.; Webb, R.I.; Schembri, M.A. (2007a). The role of F9 fimbriae of uropathogenic Escherichia coli in biofilm formation. Microbiology, 1350-0872 153 2321 2331
49 - G. C. Ulett, J. Valle, C. Beloin, O. Sherlock, J. M. Ghigo, M. A. Schembri, 2007b Functional analysis of antigen 43 in uropathogenic Escherichia coli reveals a role in long-term persistence in the urinary tract. Infection and Immunity 75 7 3233 3244 0099-9567
50 - M. Velasco, J. P. Horcajada, J. Mensa, A. Moreno-Martinez, J. Vila, J. A. Martinez, J. Ruiz, M. Barranco, G. Roig, E. Soriano, 2001 Decreased invasive capacity of quinolone-resistant Escherichia coli in patients with urinary tract infections Clinical of Infectious Diseases, 33 10 1682 1686 1058-4838
51 - Vidal, O.; Longin, R.; Prigent-Combaret, C.; Dorel, C.; Hooreman, M.; Lejeune, P. (1998). Isolation of an Escherichia coli K-12 mutant strain able to form biofilms on inert surfaces: involvement of a new ompR allele that increases curli expression. Journal of Bacteriology, 0021-9193 9 180 2442 2449
52 - Vila, J.; Simon, K.; Ruiz, J.; Horcajada, J.P.; Velasco, M.; Barranco, M.; et al. (2002). Are quinolone-resistant uropathogenic Escherichia coli less virulent? Journal of Infectious Diseases, 0022-1899 7 186 1039 1042
53 - J. W. Warren, E. Abrutyn, J. R. Hebel, J. R. Johnson, A. J. Schaeffer, W. E. Stamm, 1999 Guidelines for antimicrobial treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in womenInfectious Diseases Society of America (IDSA). Clinical Infectious Diseases 29 4 745 758 1058-4838
54 - R. A. Welch, V. Burland, G. Plunkett, P. Redford, P. Roesch, D. Rasko, et al. 2002 Extensive mosaic structure revealed by the complete genome sequence of uropathogenic Escherichia coliProcedings of the National Academy of Sciences of the United States of America, 99 26 17020 17024ISNN 0027-8424.
55 - A. P. White, D. L. Gibson, S. K. Collinson, P. A. Banser, W. W. Kay, 2003 Extracellular polysaccharides associated with thin aggregative fimbriae of Salmonella enterica serovar enteritidisJournal of Bacteriology, 185 18 5398 5407 0021-9193
56 - X. R. Wu, T. T. Sun, J. J. Medina, 1996 In vitro binding of type 1-fimbriated Escherichia coli to uroplakins Ia and Ib: Relation to urinary tract infections Procedings of the National Academy of Sciences of the United States of America, 93 18 9630 9635 0027-8424
57 - G. G. Zhanel, T. L. Hisanaga, N. M. Laing, M. R. De Corby, K. A. Nichol, et al. 2006Antibiotic resistence in Escherichia coli outpatient urinary isolates: final results from the North American Urinary Tract Infection Collaborative Alliance (NAUTICA). International Journal of Antimicrobial Agents, 27 6 468 475 0924-8579