Detailed Histopathological Examination Contributes to the Assessment of Escherichia Coli Urovirulence

Johnson, James R.; Berggren, Terriel; Newburg, David S.; McCluer, Robert H.

doi:10.1016/s0022-5347(17)37507-9

Cited by 12 publications

(7 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Coordinate regulation among fimbrial operons has been described previously and may provide an explanation for this observation (17,44). P fimbriae, argued as being virulence factors during UTI (43), are found downregulated here in vivo despite the presence of P-fimbrial Gal-Gal receptors in mice (22,32). Our microarray experiments suggest that a better way to study the importance of other adherence factors may be use of a Fim-deficient UPEC mutant.…”

Section: Discussionsupporting

confidence: 80%

Transcriptome of Uropathogenic Escherichia coli during Urinary Tract Infection

Snyder¹,

et al. 2004

View full text Add to dashboard Cite

A uropathogenic Escherichia coli strain CFT073-specific DNA microarray that includes each open reading frame was used to analyze the transcriptome of CFT073 bacteria isolated directly from the urine of infected CBA/J mice. The in vivo expression profiles were compared to that of E. coli CFT073 grown statically to exponential phase in rich medium, revealing the strategies this pathogen uses in vivo for colonization, growth, and survival in the urinary tract environment. The most highly expressed genes overall in vivo encoded translational machinery, indicating that the bacteria were in a rapid growth state despite specific nutrient limitations. Expression of type 1 fimbriae, a virulence factor involved in adherence, was highly upregulated in vivo. Five iron acquisition systems were all highly upregulated during urinary tract infection, as were genes responsible for capsular polysaccharide and lipopolysaccharide synthesis, drug resistance, and microcin secretion. Surprisingly, other fimbrial genes, such as pap and foc/sfa, and genes involved in motility and chemotaxis were downregulated in vivo. E. coli CFT073 grown in human urine resulted in the upregulation of iron acquisition, capsule, and microcin secretion genes, thus partially mimicking growth in vivo. On the basis of gene expression levels, the urinary tract appears to be nitrogen and iron limiting, of high osmolarity, and of moderate oxygenation. This study represents the first assessment of any E. coli pathotype's transcriptome in vivo and provides specific insights into the mechanisms necessary for urinary tract pathogenesis.Urinary tract infections (UTIs) are a serious health concern. Forty to 50% of women experience at least one UTI, leading to an estimated 8 million annual physician visits in the United States alone (39, 46). Uropathogenic Escherichia coli (UPEC) is by far the most common etiological agent of all UTIs. UPEC strain CFT073, derived from the clonal group O6:K2:H1 (26), was originally isolated from the blood and urine of a woman diagnosed with acute pyelonephritis (28). It is considered a prototype of the O6 serogroup, one of the most prevalent UPEC clonal lines (23,24). The virulence of this strain was reproduced in the well-established CBA mouse model of ascending UTI (28). In addition to numerous virulence studies, the genome of E. coli CFT073 has recently been sequenced and compared to that of enterohemorrhagic E. coli EDL933 and the nonpathogenic laboratory strain E. coli MG1655 (42).Mutations have been introduced into a number of candidate virulence genes in UPEC, leading to attenuated mutants in experimental UTI. These include fim, encoding type 1 fimbria (7, 13), sat, encoding secreted autotransporter toxin (14), cnf-1, encoding cytotoxic necrotizing factor (36), tonB, involved in iron transport (40), proP, involved in osmoprotectant transport (8), and degS (35). Large-scale screens for virulence factors of UPEC have also identified factors that aid UPEC during growth in urine (38) and have implicated capsule, lipopolysaccharide, ...

show abstract

Section: Discussionsupporting

confidence: 80%

Transcriptome of Uropathogenic Escherichia coli during Urinary Tract Infection

Snyder¹,

et al. 2004

View full text Add to dashboard Cite

show abstract

“…Although others have assessed the interaction of E. coli strains and mouse bladder (1,5,8,21) or the development of cystitis and pyelonephritis following experimental challenge of mice or nonhuman primates with E. coli (16,31,32), this is the first study to assess differences between the uropathogenicities of pyelonephritis and cystitis strains of E. coli in an animal model of UTI. We chose to use the transurethrally challenged mouse model which was originally described by Hagberg et al (9), who documented that a P-fimbria-expressing strain colonized the kidney better than P-fimbria-negative strains.…”

Section: Discussionmentioning

confidence: 99%

Comparison of Escherichia Coli Strains Recovered From Human Cystitis and Pyelonephritis Infections in Transurethrally Challenged Mice

Johnson¹,

Lockatell²,

Russell³

et al. 1999

The Journal of Urology

View full text Add to dashboard Cite

Urinary tract infection, most frequently caused by Escherichia coli, is one of the most common bacterial infections in humans. A vast amount of literature regarding the mechanisms through which E. coli induces pyelonephritis has accumulated. Although cystitis accounts for 95% of visits to physicians for symptoms of urinary tract infections, few in vivo studies have investigated possible differences between E. coli recovered from patients with clinical symptoms of cystitis and that from patients with symptoms of pyelonephritis. Epidemiological studies indicate that cystitis-associated strains appear to differ from pyelonephritis-associated strains in elaboration of some putative virulence factors. With transurethrally challenged mice we studied possible differences using three each of the most virulent pyelonephritis and cystitis E. coli strains in our collection. The results indicate that cystitis strains colonize the bladder more rapidly than do pyelonephritis strains, while the rates of kidney colonization are similar. Cystitis strains colonize the bladder in higher numbers, induce more pronounced histologic changes in the bladder, and are more rapidly eliminated from the mouse urinary tract than pyelonephritis strains. These results provide evidence that cystitis strains differ from pyelonephritis strains in this model, that this model is useful for the study of the uropathogenicity of cystitis strains, and that it would be unwise to use pyelonephritis strains to study putative virulence factors important in the development of cystitis.Although the bladder, particularly in women, is often exposed to bacteria and although urine generally supports bacterial growth, the combined effects of bladder emptying by urination and an intrinsic defense mechanism associated with bladder epithelium assist in resisting bacterial infection of the bladder (4, 28, 29). However, a breach of natural bladder defense mechanisms resulting from anatomical abnormalities of the urinary tract or, more commonly, virulence factors expressed by the colonizing bacteria results in urinary tract infection (UTI). Symptomatic UTI is manifest in two syndromes. One is acute pyelonephritis clinically identified by flank pain and fever and generally perceived as being a kidney infection. The second is cystitis, characterized by dysuria and increased frequency and urgency of urination, which is generally perceived to be a bladder infection and accounts for 95% of all visits to physicians for UTIs (7).In the normal urinary tract, most UTIs are caused by Escherichia coli. Studies on the uropathogenicity of E. coli have focused primarily on the development of pyelonephritis. Epidemiologic studies have implicated adhesins, particularly P fimbriae, and other factors, such as hemolysin, in the development of acute pyelonephritis; some of these have been confirmed to be virulence factors by in vitro and in vivo studies (9,10,(18)(19)(20). Only recently have epidemiologic studies begun to focus on cystitis, the more frequent UTI syndrome. Although some put...

show abstract

“…The presence and expression of pap genes is epidemiologically linked with pyelonephritis-causing E. coli strains (18), but the role of P fimbriae in virulence has not been well defined. Earlier studies in our laboratory found no difference in murine urinary tract colonization or histology when deletions were made in both copies of the pap operon in E. coli CFT073 (denoted as strain UPEC76) (26) despite the presence of P fimbrial receptors in mice (19,29). However, it has been argued that this adhesin represents a virulence factor in other UTI studies (35,53).…”

mentioning

confidence: 85%

Coordinate Expression of Fimbriae in Uropathogenic Escherichia coli

Snyder¹,

et al. 2005

View full text Add to dashboard Cite

Uropathogenic Escherichia coli is the most common etiological agent of urinary tract infections. Bacteria can often express multiple adhesins during infection in order to favor attachment to specific niches within the urinary tract. We have recently demonstrated that type 1 fimbria, a phase-variable virulence factor involved in adherence, was the most highly expressed adhesin during urinary tract infection. Here, we examine whether the expression of type 1 fimbriae can affect the expression of other adhesins. Type 1 fimbrial phase-locked mutants of E. coli strain CFT073, which harbors genes for numerous adhesins, were employed in this study. CFT073-specific DNA microarray analysis of these strains demonstrates that the expression of type 1 fimbriae coordinately affects the expression of P fimbriae in an inverse manner. This represents evidence for direct communication between genes relating to pathogenesis, perhaps to aid the sequential occupation of different urinary tract tissues. While the role of type 1 fimbriae during infection has been clear, the role of P fimbriae must be further defined to assert the relevance of coordinated regulation in vivo. Therefore, we examined the ability of P fimbrial isogenic mutants, constructed in a type 1 fimbrial-negative background, to compete in the murine urinary tract over a period of 168 h. No differences in the colonization of these mutants were observed. However, comparison of these results with previous studies suggests that inversely coordinated expression of adhesin gene clusters does occur in vivo. Interestingly, the mutant that was incapable of expressing either type 1 or P fimbriae compensated by synthesizing F1C fimbriae.Uropathogenic Escherichia coli (UPEC) strains cause the majority of all urinary tract infections (UTIs). Forty to 50% of women experience at least one UTI during their lifetime, leading to an estimated 8 million physician visits annually in the United States (39, 55). Recent efforts to understand the mechanisms of virulence in this important pathogen include the sequencing of UPEC (52), complete transcriptome analysis (45), signature-tagged mutagenesis (4), and differential fluorescence induction (33). These studies collectively implicate adhesins, iron acquisition systems, capsules, lipopolysaccharides, and toxins in UPEC pathogenesis.Adherence to host tissues is often the first step towards colonization; thus, adhesins are essential for pathogenesis. The recent sequencing of UPEC strain CFT073, along with previous virulence studies, has predicted or demonstrated as many as 12 fimbrial gene clusters in this strain (5, 17, 52). Many fimbrial and afimbrial adhesins are phase variable (28, 34), including the most ubiquitous type 1 fimbriae encoded by the fim gene cluster. The expression of type 1 fimbriae is controlled by a promoter situated on an invertible element of DNA, also referred to as the fim switch (1). Bacteria are phase on, and type 1 fimbriae are expressed when the promoter faces the direction of fimA, which encodes the main structur...

show abstract

Detailed Histopathological Examination Contributes to the Assessment of Escherichia Coli Urovirulence

Cited by 12 publications

References 24 publications

Transcriptome of Uropathogenic Escherichia coli during Urinary Tract Infection

Transcriptome of Uropathogenic Escherichia coli during Urinary Tract Infection

Comparison of Escherichia Coli Strains Recovered From Human Cystitis and Pyelonephritis Infections in Transurethrally Challenged Mice

Coordinate Expression of Fimbriae in Uropathogenic Escherichia coli

Contact Info

Product

Resources

About