Complex Interplay between Type 1 Fimbrial Expression and Flagellum-Mediated Motility of Uropathogenic Escherichia coli

Abstract

Type 1 fimbriae and flagella have been previously shown to contribute to the virulence of uropathogenic Escherichia coli (UPEC) within the urinary tract. In this study, the relationship between motility and type 1 fimbrial expression was tested for UPEC strain CFT073 by examining the phenotypic effect of fimbrial expression on motility and the effect that induction of motility has on type 1 fimbrial expression. While constitutive expression of type 1 fimbriae resulted in a significant decrease in motility and flagellin expression (P < 0.0001), a loss of type 1 fimbrial expression did not result in increased motility. Additionally, hypermotility and flagellar gene over-and underexpression were not observed to affect the expression of type 1 fimbriae. Hence, it appeared that the relationship between type 1 fimbrial expression and motility is unidirectional, where the overexpression of type 1 fimbriae dramatically affects motility and flagellum expression but not vice versa. Moreover, the constitutive expression of type 1 fimbriae in UPEC cystitis isolate F11 and the laboratory strain E. coli K-12 MG1655 also resulted in decreased motility, suggesting that this phenomenon is not specific to CFT073 or UPEC in general. Lastly, by analyzing the repression of motility caused by constitutive type 1 fimbrial expression, it was concluded that the synthesis and presence of type 1 fimbriae at the bacterial surface is only partially responsible for the repression of motility, as evidenced by the partial restoration of motility in the CFT073 fim L-ON ⌬fimAICDFGH mutant. Altogether, these data provide further insight into the complex interplay between type 1 fimbrial expression and flagellum-mediated motility.Uropathogenic Escherichia coli (UPEC) causes the majority of urinary tract infections in otherwise healthy individuals. Studies suggest that up to 95% of all urinary tract infections develop in an ascending manner (3), beginning with periurethral colonization, followed by bladder infection (cystitis) and in some cases, if left untreated, ascension of the ureters to the kidney (pyelonephritis

The fimbriae activator MatA switches off motility in Escherichia coli by repression of the flagellar master operon flhDC

“…Flagellar synthesis is decreased in cells attached to plastic surfaces as compared with freeliving bacteria (Prigent-Combaret et al, 1999) as well as during microcolony formation on epithelial cells (Cleary et al, 2004). Constitutive expression of type 1 fimbriae, an essential virulence factor in UTIs (Connell et al, 1996), has been shown to decrease motility of UPEC (Bryan et al, 2006;Lane et al, 2007a), partially due to the abundance of fimbrial structures at the cell surface (Lane et al, 2007a). Subsequent screening of factors that participate in a decreased-motility phenotype identified four transcriptional regulators, LrhA, Lrp, SlyA and P fimbriae protein PapX, that partially restore motility without affecting type 1 fimbriae expression (Simms & Mobley, 2008a).…”

Genotypic characterization of virulence factors in Escherichia coli strains from patients with cystitis

“…coli is the major causative agent in human UTIs, one of the most common bacterial infections. In most cases, uropathogenic clones are selected from the fecal flora, and the pathogenic potential of E. coli strains is thought to be dependent on the presence of VFs 19,23 . Based on their components and products called virulence factors, E. coli cells attach selectively to the mucosa uro-epithelium, promoting colonization and persisting in the urinary tract, inducing, then, a local inflammatory response and sometimes to promote tissue lesions 23,29 .…”

“…Cystitis (lower UTI) is characterized by pelvic discomfort, especially pre -and immediately post void, frequent or urgent voiding and suprapubic pain. Acute pyelonephritis (upper UTI) is, most of the times, a more serious problem and is clinically identified by the fever, flank pain, nausea and, sometimes, vomiting 19,22,23 .…”

A Conserved PapB Family Member, TosR, Regulates Expression of the Uropathogenic Escherichia coli RTX Nonfimbrial Adhesin TosA while Conserved LuxR Family Members TosE and TosF Suppress Motility

“…To detect TosA, total protein from the tos deletion mutants, E. coli CFT073, or E. coli CFT073 carrying the pBAD overexpression constructs was collected and Western blotting was performed. Briefly, equal amounts of total proteins, determined using a Pierce BCA protein assay kit (Thermo Scientific), from specific constructs were resolved, transferred, and blotted with polyclonal anti-TosA antibodies (27), polyclonal antiFliC antibodies (37), or an anti-His 6 antibody (Invitrogen).…”

“…It is now recognized, however, that adherence genes and flagellar genes can be reciprocally coordinated (34)(35)(36)(37)(38)(39). In this network, it is logical that an adherent bacterium should not be motile and a motile bacterium should not be adherent.…”