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

Bateman, Stacey L.; Stapleton, Ann E.; Stamm, Walter E.; Hooton, Thomas M.; Seed, Patrick C.

doi:10.1099/mic.0.066472-0

Cited by 12 publications

(21 citation statements)

References 62 publications

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“…2A; P < 0.05). FimX is another accessory tyrosine recombinase that contributes to turning 'on' fimS in UPEC (Bateman et al, 2013). All of the ST131 strains used for this analysis contained the fimX gene, and thus fimX transcript levels were also examined.…”

Section: Resultsmentioning

confidence: 99%

Comprehensive analysis of type 1 fimbriae regulation in fimB‐null strains from the multidrug resistant Escherichia coli ST131 clone

Sarkar

Roberts

Phan

et al. 2016

Molecular Microbiology

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SummaryUropathogenic Escherichia coli (UPEC) of sequence type 131 (ST131) are a pandemic multidrug resistant clone associated with urinary tract and bloodstream infections. Type 1 fimbriae, a major UPEC virulence factor, are essential for ST131 bladder colonization. The globally dominant sub-lineage of ST131 strains, clade C/H30-R, possess an ISEc55 insertion in the fimB gene that controls phase-variable type 1 fimbriae expression via the invertible fimS promoter. We report that inactivation of fimB in these strains causes altered regulation of type 1 fimbriae expression. Using a novel read-mapping approach based on Illumina sequencing, we demonstrate that 'off' to 'on' fimS inversion is reduced in these strains and controlled by recombinases encoded by the fimE and fimX genes. Unlike typical UPEC strains, the nucleoid-associated H-NS protein does not strongly repress fimE transcription in clade C ST131 strains. Using a genetic screen to identify novel regulators of fimE and fimX in the clade C ST131 strain EC958, we defined a new role for the guaB gene in the regulation of type 1 fimbriae and in colonisation of the mouse bladder. Our results provide a comprehensive analysis of type 1 fimbriae regulation in ST131, and highlight important differences in its control compared to non-ST131 UPEC.

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Section: Resultsmentioning

confidence: 99%

Comprehensive analysis of type 1 fimbriae regulation in fimB‐null strains from the multidrug resistant Escherichia coli ST131 clone

Sarkar

Roberts

Phan

et al. 2016

Molecular Microbiology

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“…Regarding T1P, UPEC isolates carry a variable complement of alternative recombinases (ipuA, ipuB, fimX) that themselves have varying effects on fimS inversion; ipuA inverts bidirectionally, whereas fimX favors OFF-to-ON switching (29,30,56). FimX also inverts another genomic locus, hyxR, using different IRs (14). Even with a similar complement of recombinases, further regulatory variation may exist.…”

Section: Discussionmentioning

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%

“…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 temperature, pH, osmolality, and the stress and stringent responses (15)(16)(17)(18)(19).…”

mentioning

confidence: 99%

“…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.…”

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confidence: 99%

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Comprehensive mutagenesis of the fimS promoter regulatory switch reveals novel regulation of type 1 pili in uropathogenic Escherichia 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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Pathogenic Mechanisms of Uropathogens

O’Rourke¹,

Cadieux

2019

The Role of Bacteria in Urology

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

Cited by 12 publications

References 62 publications

Comprehensive analysis of type 1 fimbriae regulation in fimB‐null strains from the multidrug resistant Escherichia coli ST131 clone

Comprehensive analysis of type 1 fimbriae regulation in fimB‐null strains from the multidrug resistant Escherichia coli ST131 clone

Comprehensive mutagenesis of the fimS promoter regulatory switch reveals novel regulation of type 1 pili in uropathogenic Escherichia coli

Pathogenic Mechanisms of Uropathogens

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