Regulation of Type 1 Fimbriae by Unlinked FimB- and FimE-Like Recombinases in Uropathogenic
            <i>Escherichia coli</i>
            Strain CFT073

Bryan, Andrew; Roesch, Paula L.; Davis, Lindsay; Moritz, Rebecca; Pellett, Sabine; Welch, Rodney A.

doi:10.1128/iai.74.2.1072-1083.2006

Cited by 74 publications

(114 citation statements)

References 83 publications

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“…(Bryan et al, 2006), and that ipuA and ipuB were present in commensal (15 %) and UPEC (23.7 %) isolates in statistically equal abundance (Table 3). In contrast, fimX was highly prevalent among UPEC (83.2 %), but not commensal isolates (36 %; P,0.0001), and was more prevalent in lower (87.5 %) than upper UTI isolates (74 %; P50.03) ( Table 3).…”

Section: Resultsmentioning

confidence: 97%

“…The orientation of the invertible type 1 pili promoter region (fimS) (Abraham et al, 1985) is determined by the action of multiple tyrosine recombinases. UPEC strains are known to possess up to five Fim-like tyrosine recombinases (FimB, FimE, FimX, IpuA and IpuB) based on sequence homology, and all but IpuB are have been shown to invert fimS (Bryan et al, 2006;Gally et al, 1996;Hannan et al, 2008;Klemm, 1986;McClain et al, 1991;Xie et al, 2006) with differing biochemical activities: FimE inverts the promoter from ON to OFF, FimB catalyses bidirectional inversion, but favours OFF to ON, IpuA also has bidirectional activity, while FimX is able to invert fimS from OFF to ON.…”

Section: Introductionmentioning

confidence: 99%

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The type 1 pili regulator gene fimX and pathogenicity island PAI-X as molecular markers of uropathogenic Escherichia coli

et al. 2013

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Uropathogenic Escherichia coli (UPEC) fall within a larger group of isolates producing extraintestinal disease. UPEC express type 1 pili as a critical virulence determinant mediating adherence to and invasion into urinary tract tissues. Type 1 pili expression is under regulation by a family of site-specific recombinases, including FimX, which is encoded from a genomic island called PAI-X for pathogenicity island of FimX. Using a new multiplex PCR, fimX and the additional PAI-X genes were found to be highly associated with UPEC (144/173583.2 %), and more prevalent in UPEC of lower urinary tract origin (105/120587.5 %) than upper urinary tract origin (39/53574 %; P,0.05) or commensal isolates (28/78536 %; P¡0.0001). The Fim-like recombinase gene fimX is the only family member that has a significant association with UPEC compared to commensal isolates. Our results indicate PAI-X genes, including the type 1 pili regulator gene fimX, are highly prevalent among UPEC isolates and have a strong positive correlation with genomic virulence factors, suggesting a potential role for PAI-X in the extraintestinal pathogenic E. coli lifestyle.

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Section: Resultsmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

The type 1 pili regulator gene fimX and pathogenicity island PAI-X as molecular markers of uropathogenic Escherichia coli

et al. 2013

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“…Type 1 pili are assembled by the chaperone-usher pathway (8,9), and FimH plays a key role in initiation of pilus assembly in UPEC (10). Expression of type 1 pili is primarily controlled by transcriptional phase regulation: several recombinase genes mediate inversion of a promoter element controlling transcription of all structural genes required for pilus assembly (11)(12)(13). The recombinase genes, in turn, are regulated by several environmental cues (e.g., growth temperature and agitation) (14) and may impact the regulation of other pilus operons (15).…”

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confidence: 99%

Positive selection identifies an in vivo role for FimH during urinary tract infection in addition to mannose binding

Chen

Hung

Pinkner

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

168

209

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FimH, the type 1 pilus adhesin of uropathogenic Escherichia coli (UPEC), contains a receptor-binding domain with an acidic binding pocket specific for mannose. The fim operon, and thus type 1 pilus production, is under transcriptional control via phase variation of an invertible promoter element. FimH is critical during urinary tract infection for mediating colonization and invasion of the bladder epithelium and establishment of intracellular bacterial communities (IBCs). In silico analysis of FimH gene sequences from 279 E. coli strains identified specific amino acids evolving under positive selection outside of its mannose-binding pocket. Mutating two of these residues (A27V/V163A) had no effect on phase variation, pilus assembly, or mannose binding in vitro. However, compared to wild-type, this double mutant strain exhibited a 10,000-fold reduction in mouse bladder colonization 24 h after inoculation and was unable to form IBCs even though it bound normally to mannosylated receptors in the urothelium. In contrast, the single A62S mutation altered phase variation, reducing the proportion of piliated cells, reduced mannose binding 8-fold, and decreased bladder colonization 30-fold in vivo compared to wild-type. A phase-locked ON A62S mutant restored virulence to wild-type levels even though in vitro mannose binding remained impaired. Thus, positive selection analysis of FimH has separated mannose binding from in vivo fitness, suggesting that IBC formation is critical for successful infection of the mammalian bladder, providing support for more general use of in silico positive selection analysis to define the molecular underpinnings of bacterial pathogenesis.type 1 pili ͉ uropathogenic Escherichia coli

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“…However, FimE can mediate OFF-to-ON inversion in vivo (28). In addition to fimB and fimE, UPEC strains often carry other unlinked recombinases (such as fimX and ipuA) whose products also mediate fimS inversion (14,29,30), and even the presence of the "core" fimB gene can vary (31). Thus, both the presence and function of recombinase vary among E. coli, highlighting the importance of studying T1P directly in pathogenic E. coli strains.…”

mentioning

confidence: 99%

“…This method may enable comprehensive studies of phase variation in other pathogens and other regulated DNA dynamics in general. genetic manipulation, but, as mentioned above, regulation relevant to infection may differ in clinical isolates (14,(29)(30)(31).…”

mentioning

confidence: 99%

Comprehensive mutagenesis of thefimSpromoter regulatory switch reveals novel regulation of type 1 pili in uropathogenicEscherichia coli

Zhang

Susanto

Wan

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Type 1 pili (T1P) are major virulence factors for uropathogenic Escherichia coli (UPEC), which cause both acute and recurrent urinary tract infections. T1P expression therefore is of direct relevance for disease. T1P are phase variable (both piliated and nonpiliated bacteria exist in a clonal population) and are controlled by an invertible DNA switch (fimS), which contains the promoter for the fim operon encoding T1P. Inversion of fimS is stochastic but may be biased by environmental conditions and other signals that ultimately converge at fimS itself. Previous studies of fimS sequences important for T1P phase variation have focused on laboratory-adapted E. coli strains and have been limited in the number of mutations or by alteration of the fimS genomic context. We surmounted these limitations by using saturating genomic mutagenesis of fimS coupled with accurate sequencing to detect both mutations and phase status simultaneously. In addition to the sequences known to be important for biasing fimS inversion, our method also identifies a previously unknown pair of 5′ UTR inverted repeats that act by altering the relative fimA levels to control phase variation. Thus we have uncovered an additional layer of T1P regulation potentially impacting virulence and the coordinate expression of multiple pilus systems.urinary tract infection | fimS | type 1 pili | phase variation | saturating chromosomal mutagenesis U rinary tract infections (UTIs) are common infections that mostly affect women with an annual cost of billions of dollars (1). They are caused mainly by uropathogenic Escherichia coli (UPEC), which rely on several virulence factors to cause disease (2); type 1 pili (T1P) are perhaps the most important of these (3). T1P present a tip adhesin, FimH, that binds specifically to mannose, which is found on several glycosylated surface proteins, such as uroplakins and α1-and β3-integrins (4, 5), in the mammalian bladder. Binding to mannosylated proteins initiates a cascade of events including UPEC invasion of host tissues (2), formation of intracellular structures (6), and activation of the host immune response (7). The interplay among these events determines the outcome of infection (8), ranging from full clearance to chronic active cystitis. T1P are important for most of these UTI stages and demonstrate dynamic regulation of expression that can be seen directly in human infections and urine (9, 10).Thus, understanding T1P regulation is fundamental to understanding UTI. T1P have been well studied (11), mostly in laboratory-adapted E. coli strains. T1P are encoded by the fim operon; their expression is phase variable via inversion of fimS, a chromosomal DNA segment containing the fim promoter (12). This binary epigenetic switch results in bacteria switching between fimbriated and nonfimbriated states. Inversion is mediated by the FimB and FimE recombinases, whose genes are located immediately upstream of fimS (13) and are found in most E. coli strains (14). Inversion is influenced by numerous signals, such as temperatu...

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Regulation of Type 1 Fimbriae by Unlinked FimB- and FimE-Like Recombinases in Uropathogenic Escherichia coli Strain CFT073

Cited by 74 publications

References 83 publications

The type 1 pili regulator gene fimX and pathogenicity island PAI-X as molecular markers of uropathogenic Escherichia coli

The type 1 pili regulator gene fimX and pathogenicity island PAI-X as molecular markers of uropathogenic Escherichia coli

Positive selection identifies an in vivo role for FimH during urinary tract infection in addition to mannose binding

Comprehensive mutagenesis of thefimSpromoter regulatory switch reveals novel regulation of type 1 pili in uropathogenicEscherichia coli

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