Insights into a Multidrug Resistant Escherichia coli Pathogen of the Globally Disseminated ST131 Lineage: Genome Analysis and Virulence Mechanisms

Totsika, Makrina; Beatson, Scott A.; Sarkar, Sohinee; Phan, Minh Duy; Petty, Nicola K.; Bachmann, Nathan L.; Szubert, Marek; Sidjabat, Hanna E.; Paterson, David L.; Upton, Mathew; Schembri, Mark A.

doi:10.1371/journal.pone.0026578

Cited by 208 publications

(294 citation statements)

References 42 publications

(60 reference statements)

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“…The gene was annotated as espC (a member of the serine protease autotransporters of Enterobacteriaceae, [SPATE] family). The gene is contained in a genetic island reported previously as ROD3 in ST131 strain EC958 (Totsika et al 2011), but is not identical to the first description of an espC pathogenicity island that was originally reported in EPEC (Stein et al 1996;Mellies et al 2001;Schmidt and Hensel 2004). The sequence identity/similarity of the EPEC espC and EC958 espC was 68% for DNA and 69%/73% for protein.…”

Section: −16mentioning

confidence: 74%

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Systematic longitudinal survey of invasive Escherichia coli in England demonstrates a stable population structure only transiently disturbed by the emergence of ST131

et al. 2017

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Escherichia coli associated with urinary tract infections and bacteremia has been intensively investigated, including recent work focusing on the virulent, globally disseminated, multidrug-resistant lineage ST131. To contextualize ST131 within the broader E. coli population associated with disease, we used genomics to analyze a systematic 11-yr hospital-based survey of E. coli associated with bacteremia using isolates collected from across England by the British Society for Antimicrobial Chemotherapy and from the Cambridge University Hospitals NHS Foundation Trust. Population dynamics analysis of the most successful lineages identified the emergence of ST131 and ST69 and their establishment as two of the five most common lineages along with ST73, ST95, and ST12. The most frequently identified lineage was ST73. Compared to ST131, ST73 was susceptible to most antibiotics, indicating that multidrug resistance was not the dominant reason for prevalence of E. coli lineages in this population. Temporal phylogenetic analysis of the emergence of ST69 and ST131 identified differences in the dynamics of emergence and showed that expansion of ST131 in this population was not driven by sequential emergence of increasingly resistant subclades. We showed that over time, the E. coli population was only transiently disturbed by the introduction of new lineages before a new equilibrium was rapidly achieved. Together, these findings suggest that the frequency of E. coli lineages in invasive disease is driven by negative frequency-dependent selection occurring outside of the hospital, most probably in the commensal niche, and that drug resistance is not a primary determinant of success in this niche.

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Section: −16mentioning

confidence: 74%

“…Mapping against the reference strain EC958 also enabled us to analyze the presence of the reported ST131 genomic island ROD3 (Totsika et al 2011) and the type 6 secretion system (T6SS) across the whole invasive E. coli population in England (Supplemental Fig. S4).…”

Section: Distribution Of Virulence Factorsmentioning

confidence: 99%

Systematic longitudinal survey of invasive Escherichia coli in England demonstrates a stable population structure only transiently disturbed by the emergence of ST131

et al. 2017

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“…Even with a similar complement of recombinases, further regulatory variation may exist. ST131 strain EC958 carries an insertion sequence that inactivates fimB but retains OFF-to-ON switching ability, presumably through FimX or a noncanonical activity of FimE (31). Finally, there are hints of evolutionary interactions between the expression of T1P and other virulence factors.…”

Section: Discussionmentioning

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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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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An integrated network analysis identifies how ArcAB enables metabolic oscillations in the nitric oxide detoxification network of Escherichia coli

Sacco

Adolfsen

Brynildsen

2017

Biotechnology Journal

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The virulences of many pathogens depend on their abilities to detoxify the immune antimicrobial nitric oxide (NO•). The functions of bacterial NO• detoxification machinery depend on oxygen (O ), with O inhibiting some enzymes, whereas others use it as a substrate. Previously, Escherichia coli NO• detoxification was found to be highly attenuated under microaerobic conditions and metabolic oscillations were observed. The oscillations in [NO•] and [O ] were found to result from the inhibitory action of NO• on aerobic respiration, the catalytic inactivation of NO• by Hmp (an NO• dioxygenase), and an imbalanced competition for O between Hmp and cytochrome terminal oxidase activity. Here the authors investigated the role of the ArcAB two component system (TCS) in microaerobic NO• detoxification. The authors observed that wild-type, ΔarcA, and ΔarcB had comparable initial NO• clearance times; however, the mutant cultures failed to exhibit [NO•] and [O ] oscillations. Using an approach that employed experimentation and computational modeling, the authors found that the loss of oscillations in ΔarcA was due to insufficient induction of cytochrome bd-I expression. Collectively, these results establish ArcAB as a TCS that influences NO• detoxification in E. coli within the physiologically-relevant microaerobic regime.

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Insights into a Multidrug Resistant Escherichia coli Pathogen of the Globally Disseminated ST131 Lineage: Genome Analysis and Virulence Mechanisms

Cited by 208 publications

References 42 publications

Systematic longitudinal survey of invasive Escherichia coli in England demonstrates a stable population structure only transiently disturbed by the emergence of ST131

Systematic longitudinal survey of invasive Escherichia coli in England demonstrates a stable population structure only transiently disturbed by the emergence of ST131

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

An integrated network analysis identifies how ArcAB enables metabolic oscillations in the nitric oxide detoxification network of Escherichia coli

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