scholarly journals The Norepinephrine Metabolite 3,4-Dihydroxymandelic Acid Is Produced by the Commensal Microbiota and Promotes Chemotaxis and Virulence Gene Expression in Enterohemorrhagic Escherichia coli

2017 ◽  
Vol 85 (10) ◽  
Author(s):  
Nitesh Sule ◽  
Sasi Pasupuleti ◽  
Nandita Kohli ◽  
Rani Menon ◽  
Lawrence J. Dangott ◽  
...  
Keyword(s):  
Gene Expression ◽  
Escherichia Coli ◽  
Virulence Gene ◽  
The United States ◽  
Enterohemorrhagic Escherichia Coli ◽  
Dependent Manner ◽  
Content Type ◽  
Virulence Gene Expression ◽  
E Coli ◽  
Commensal Microbiota

ABSTRACT Enterohemorrhagic Escherichia coli (EHEC) is a commonly occurring foodborne pathogen responsible for numerous multistate outbreaks in the United States. It is known to infect the host gastrointestinal tract, specifically, in locations associated with lymphoid tissue. These niches serve as sources of enteric neurotransmitters, such as epinephrine and norepinephrine, that are known to increase virulence in several pathogens, including enterohemorrhagic E. coli. The mechanisms that allow pathogens to target these niches are poorly understood. We previously reported that 3,4-dihydroxymandelic acid (DHMA), a metabolite of norepinephrine produced by E. coli, is a chemoattractant for the nonpathogenic E. coli RP437 strain. Here we report that DHMA is also a chemoattractant for EHEC. In addition, DHMA induces the expression of EHEC virulence genes and increases attachment to intestinal epithelial cells in vitro in a QseC-dependent manner. We also show that DHMA is present in murine gut fecal contents and that its production requires the presence of the commensal microbiota. On the basis of its ability to both attract and induce virulence gene expression in EHEC, we propose that DHMA acts as a molecular beacon to target pathogens to their preferred sites of infection in vivo.

scholarly journals Reconstitution of Acetosyringone-Mediated Agrobacterium tumefaciens Virulence Gene Expression in the Heterologous Host Escherichia coli

2001 ◽  
Vol 183 (12) ◽  
pp. 3704-3711 ◽  
Author(s):  
Scott M. Lohrke ◽  
Hongjiang Yang ◽  
Shouguang Jin
Keyword(s):  
Gene Expression ◽  
Escherichia Coli ◽  
Agrobacterium Tumefaciens ◽  
Virulence Genes ◽  
Virulence Gene ◽  
Dependent Manner ◽  
Gene Encoding ◽  
Virulence Gene Expression ◽  
E Coli ◽  
Glucose Binding

ABSTRACT The ability to utilize Escherichia coli as a heterologous system in which to study the regulation ofAgrobacterium tumefaciens virulence genes and the mechanism of transfer DNA (T-DNA) transfer would provide an important tool to our understanding and manipulation of these processes. We have previously reported that the rpoA gene encoding the alpha subunit of RNA polymerase is required for the expression of lacZ gene under the control of virB promoter (virBp::lacZ) in E. colicontaining a constitutively active virG gene [virG(Con)]. Here we show that an RpoA hybrid containing the N-terminal 247 residues from E. coli and the C-terminal 89 residues from A. tumefaciens was able to significantly express virBp::lacZ in E. coli in a VirG(Con)-dependent manner. Utilization oflac promoter-driven virA and virGin combination with the A. tumefaciens rpoA construct resulted in significant inducer-mediated expression of thevirBp::lacZ fusion, and the level ofvirBp::lacZ expression was positively correlated to the copy number of the rpoA construct. This expression was dependent on VirA, VirG, temperature, and, to a lesser extent, pH, which is similar to what is observed in A. tumefaciens. Furthermore, the effect of sugars on virgene expression was observed only in the presence of thechvE gene, suggesting that the glucose-binding protein ofE. coli, a homologue of ChvE, does not interact with the VirA molecule. We also evaluated other phenolic compounds in induction assays and observed significant expression with syringealdehyde, a low level of expression with acetovanillone, and no expression with hydroxyacetophenone, similar to what occurs in A. tumefaciens strain A348 from which the virA clone was derived. These data support the notion that VirA directly senses the phenolic inducer. However, the overall level of expression of thevir genes in E. coli is less than what is observed in A. tumefaciens, suggesting that additional gene(s) from A. tumefaciens may be required for the full expression of virulence genes in E. coli.

Transcriptional Activator OvrA Encoded in O Island 19 Modulates Virulence Gene Expression in Enterohemorrhagic Escherichia coli O157:H7

2019 ◽  
Author(s):  
Bin Liu ◽  
Junyue Wang ◽  
Lu Wang ◽  
Peng Ding ◽  
Pan Yang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Escherichia Coli ◽  
Gene Promoter ◽  
Virulence Gene ◽  
Coli Strain ◽  
Enterohemorrhagic Escherichia Coli ◽  
Bacterial Adherence ◽  
Host Cells ◽  
Virulence Gene Expression ◽  
E Coli

AbstractThe human intestinal pathogen enterohemorrhagic Escherichia coli (EHEC) O157:H7 causes bloody diarrhea, hemorrhagic colitis, and fatal hemolytic uremic syndrome. Its genome contains 177 unique O islands (OIs), which contribute largely to the high virulence and pathogenicity although most OI genes remain uncharacterized. In the current study, we demonstrated that OI-19 is required for EHEC O157:H7 adherence to host cells. Z0442 (OI-encoded virulence regulator A [OvrA]) encoded in OI-19 positively regulated bacterial adherence by activating locus of enterocyte effacement (LEE) gene expression through direct OvrA binding to the gene promoter region of the LEE gene master regulator Ler. Mouse colonization experiments revealed that OvrA promotes EHEC O157:H7 adherence in mouse intestine, preferentially the colon. Finally, OvrA also regulated virulence in other non-O157 pathogenic E. coli, including EHEC strains O145:H28 and O157:H16 and enteropathogenic E. coli strain O55:H7. Our work markedly enriches the understanding of bacterial adherence control and provides another example of laterally acquired regulators that mediate LEE gene expression.

scholarly journals Pathovar Transcriptomes

mSystems ◽  
2017 ◽  
Vol 2 (4) ◽  
Author(s):  
Amy Platenkamp ◽  
Jay L. Mellies
Keyword(s):  
Gene Expression ◽  
Escherichia Coli ◽  
Regulatory Networks ◽  
Virulence Gene ◽  
Model System ◽  
Genomic Sequences ◽  
Bacterial Strains ◽  
Content Type ◽  
Virulence Gene Expression ◽  
Link Type

ABSTRACT Archetypal pathogenic bacterial strains are often used to elucidate regulatory networks of an entire pathovar, which encompasses multiple lineages and phylogroups. With enteropathogenic Escherichia coli (EPEC) as a model system, Hazen and colleagues (mSystems 6:e00024-17, 2017, https://doi.org/10.1128/mSystems.00024-17 ) used 9 isolates representing 8 lineages and 3 phylogroups to find that isolates with similar genomic sequences exhibit similarities in global transcriptomes under conditions of growth in medium that induces virulence gene expression, and they found variation among individual isolates. Archetypal pathogenic bacterial strains are often used to elucidate regulatory networks of an entire pathovar, which encompasses multiple lineages and phylogroups. With enteropathogenic Escherichia coli (EPEC) as a model system, Hazen and colleagues (mSystems 6:e00024-17, 2017, https://doi.org/10.1128/mSystems.00024-17 ) used 9 isolates representing 8 lineages and 3 phylogroups to find that isolates with similar genomic sequences exhibit similarities in global transcriptomes under conditions of growth in medium that induces virulence gene expression. They also found variation among individual isolates. Their work illustrates the importance of moving beyond observing regulatory phenomena of a limited number of regulons in a few archetypal strains, with the possibility of correlating clinical symptoms to key transcriptional pathways across lineages and phylogroups.

scholarly journals Enterohemorrhagic Escherichia coli Virulence Regulation by Two Bacterial Adrenergic Kinases, QseC and QseE

2011 ◽  
Vol 80 (2) ◽  
pp. 688-703 ◽  
Author(s):  
Jacqueline Njoroge ◽  
Vanessa Sperandio
Keyword(s):  
Escherichia Coli ◽  
Response Regulator ◽  
Enterohemorrhagic Escherichia Coli ◽  
Dependent Manner ◽  
Content Type ◽  
E Coli ◽  
Virulence Regulation ◽  
Sensor Kinases ◽  
Virulence Factor Gene ◽  
Enterocyte Effacement

ABSTRACTThe human pathogen enterohemorrhagicEscherichia coli(EHEC) O157:H7 has two histidine sensor kinases, QseC and QseE, which respond to the mammalian adrenergic hormones epinephrine and norepinephrine by increasing their autophosphorylation. Although QseC and QseE are present in nonpathogenic strains ofE. coli, EHEC exploits these kinases for virulence regulation. To further investigate the full extent of epinephrine and its sensors' impact on EHEC virulence, we performed transcriptomic and phenotypic analyses of single and double deletions ofqseCandqseEgenes in the absence or presence of epinephrine. We showed that in EHEC, epinephrine sensing seems to occur primarily through QseC and QseE. We also observed that QseC and QseE regulate expression of the locus of enterocyte effacement (LEE) genes positively and negatively, respectively. LEE activation, which is required for the formation of the characteristic attaching and effacing (A/E) lesions by EHEC on epithelial cells, is epinephrine dependent. Regulation of the LEE and the non-LEE-contained virulence factor genenleAby QseE is indirect, through transcription inhibition of the RcsB response regulator. Finally, we show that coincubation of HeLa cells with epinephrine increases EHEC infectivity in a QseC- and QseE-dependent manner. These results genetically and phenotypically map the contributions of the two adrenergic sensors QseC and QseE to EHEC pathogenesis.

Glucose Decreases Virulence Gene Expression of Escherichia coli O157:H7

2012 ◽  
Vol 75 (4) ◽  
pp. 748-752 ◽  
Author(s):  
V. DELCENSERIE ◽  
G. LaPOINTE ◽  
T. CHARASLERTRANGSI ◽  
A. RABALSKI ◽  
M. W. GRIFFITHS
Keyword(s):  
Gene Expression ◽  
Escherichia Coli ◽  
Quorum Sensing ◽  
Shiga Toxin ◽  
Virulence Gene ◽  
Escherichia Coli O157 ◽  
Virulence Gene Expression ◽  
E Coli ◽  
Reverse Transcription Pcr ◽  
Enterocyte Effacement

Escherichia coli O157:H7 is responsible for a human toxico-infection that can lead to severe complications such as hemolytic uremic syndrome. Inside the intestine, E. coli O157:H7 forms typical attaching-effacing lesions and produces Shiga toxins. The genes that are responsible for these lesions are located in a pathogenicity island called the locus of enterocyte effacement (LEE). LEE gene expression is influenced by quorum sensing through the luxS system. In this study, the effect of glucose on the expression of several genes from LEE, on the expression of Shiga toxin genes, and on the expression of luxS was assessed with real-time, reverse transcription PCR. All concentrations of glucose (from 0.1 to 1%) were able to down-regulate genes from the LEE operon. A slight down-regulation of genes implicated in Shiga toxin expression was also observed but was significant for low doses of glucose (0.1 to 0.5%) only. A slight but significant increase in luxS expression was observed with 1% glucose. This confirms that in addition to quorum sensing, the presence or absence of nutrients such as glucose has an impact on the down- or upregulation of LEE-encoded virulence genes by the bacterium. The influence of glucose on the virulence of E. coli O157:H7 has received little attention, and these results suggest that glucose can have an important effect on the virulence of E. coli O157:H7.

scholarly journals Prevalence and Genomic Characterization of Escherichia coli O157:H7 in Cow-Calf Herds throughout California

2017 ◽  
Vol 83 (16) ◽  
Author(s):  
Jay N. Worley ◽  
Kristopher A. Flores ◽  
Xun Yang ◽  
Jennifer A. Chase ◽  
Guojie Cao ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Large Scale ◽  
Fresh Produce ◽  
Bacterial Pathogen ◽  
Virulence Gene ◽  
The United States ◽  
Pathogenic Potential ◽  
Content Type ◽  
E Coli ◽  
Cow Calf

ABSTRACT Escherichia coli serotype O157:H7 is a zoonotic food- and waterborne bacterial pathogen that causes a high hospitalization rate and can cause life-threatening complications. Increasingly, E. coli O157:H7 infections appear to originate from fresh produce. Ruminants, such as cattle, are a prominent reservoir of E. coli O157:H7 in the United States. California is one of the most agriculturally productive regions in the world for fresh produce, beef, and milk. The close proximity of fresh produce and cattle presents food safety challenges on a uniquely large scale. We performed a survey of E. coli O157:H7 on 20 farms in California to observe the regional diversity and prevalence of E. coli O157:H7. Isolates were obtained from enrichment cultures of cow feces. Some farms were sampled on two dates. Genomes from isolates were sequenced to determine their relatedness and pathogenic potential. E. coli O157:H7 was isolated from approximately half of the farms. The point prevalence of E. coli O157:H7 on farms was highly variable, ranging from zero to nearly 90%. Within farms, generally one or a few lineages were found, even when the rate of isolation was high. On farms with high isolation rates, a single clonal lineage accounted for most of the isolates. Farms that were visited months after the first visit might have had the same lineages of E. coli O157:H7. Strains of E. coli O157:H7 may be persistent for months on farms. IMPORTANCE This survey of 20 cow-calf operations from different regions of California provides an in depth look at resident Escherichia coli O157:H7 populations at the molecular level. E. coli O157:H7 is found to have a highly variable prevalence, and with whole-genome sequencing, high prevalences in herds were found to be due to a single lineage shed from multiple cows. Few repeat lineages were found between farms in this area; therefore, we predict that E. coli O157:H7 has significant diversity in this area beyond what is detected in this survey. All isolates from this study were found to have pathogenic potential based on the presence of key virulence gene sequences. This represents a novel insight into pathogen diversity within a single subtype and will inform future attempts to survey regional pathogen populations.

scholarly journals Epidemic Emergence in the United States of Escherichia coli Sequence Type 131-H30 (ST131-H30), 2000 to 2009

2017 ◽  
Vol 61 (8) ◽  
Author(s):  
James R. Johnson ◽  
Stephen Porter ◽  
Paul Thuras ◽  
Mariana Castanheira
Keyword(s):  
United States ◽  
Escherichia Coli ◽  
Single Agent ◽  
Temporal Trends ◽  
Virulence Gene ◽  
The United States ◽  
Sequence Type ◽  
Content Type ◽  
E Coli ◽  
Recent Emergence

ABSTRACT The H30 subclone of Escherichia coli sequence type 131 (ST131-H30) has become the leading antimicrobial resistance E. coli lineage in the United States and often exhibits resistance to one or both of the two key antimicrobial classes for treating Gram-negative infections, extended-spectrum cephalosporins (ESCs) and fluoroquinolones (FQs). However, the timing of and reasons for its recent emergence are inadequately defined. Accordingly, from E. coli clinical isolates collected systematically across the United States by the SENTRY Antimicrobial Surveillance Program in 2000, 2003, 2006, and 2009, 234 isolates were selected randomly, stratified by year, within three resistance categories: (i) ESC-reduced susceptibility, regardless of FQ phenotype (ESC-RS); (ii) FQ resistance, ESC susceptible (FQ-R); and (iii) FQ susceptible, ESC susceptible (FQ-S). Susceptibility profiles, phylogroup, ST, ST131 subclone, and virulence genotypes were determined, and temporal trends and between-variable associations were assessed statistically. From 2000 to 2006, concurrently with the emergence of ESC-RS and FQ-R strains, the prevalence of (virulence-associated) phylogroup B2 among such strains also rose dramatically, due entirely to rapid emergence of ST131, especially H30. By 2009, H30 was the dominant E. coli lineage overall (22%), accounting for a median of 43% of all single-agent and multidrug resistance (68% for ciprofloxacin). H30's emergence increased the net virulence gene content of resistant (especially FQ-R) isolates, giving stable overall virulence gene scores despite an approximately 4-fold expansion of the historically less virulent resistant population. These findings define more precisely the timing and tempo of H30's emergence in the United States, identify possible reasons for it, and suggest potential consequences, including more frequent and/or aggressive antimicrobial-resistant infections.

scholarly journals The Acyl-Homoserine Lactone Synthase YenI from Yersinia enterocolitica Modulates Virulence Gene Expression in Enterohemorrhagic Escherichia coli O157:H7

2013 ◽  
Vol 81 (11) ◽  
pp. 4192-4199 ◽  
Author(s):  
Y N. Nguyen ◽  
Haiqing Sheng ◽  
Rambabu Dakarapu ◽  
John R. Falck ◽  
Carolyn J. Hovde ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Yersinia Enterocolitica ◽  
Virulence Gene ◽  
Acid Resistance ◽  
Homoserine Lactone ◽  
Enterohemorrhagic Escherichia Coli ◽  
Content Type ◽  
Fecal Shedding ◽  
Virulence Gene Expression

ABSTRACTThe human pathogen enterohemorrhagicEscherichia coli(EHEC) O157:H7 colonizes the rectoanal junction (RAJ) in cattle, its natural reservoir. Colonization at the RAJ poses a serious risk for fecal shedding and contamination of the environment. We previously demonstrated that EHEC senses acyl-homoserine lactones (AHLs) produced by the microbiota in the rumen to activate thegadacid resistance genes necessary for survival through the acidic stomachs in cattle and to repress the locus of enterocyte effacement (LEE) genes important for colonization of the RAJ, but unnecessary in the rumen. Devoid of AHLs, the RAJ is the prominent site of colonization of EHEC in cattle. To determine if the presence of AHLs in the RAJ could repress colonization at this site, we engineered EHEC to express theYersinia enterocoliticaAHL synthase geneyenI, which constitutively produces AHLs, to mimic a constant exposure of AHLs in the environment. TheyenI+EHEC produces oxo-C6-homoserine lactone (oxo-C6-HSL) and had a significant reduction in LEE expression, effector protein secretion, and attaching and effacing (A/E) lesion formationin vitrocompared to the wild type (WT). TheyenI+EHEC also activated expression of thegadgenes. To assess whether AHL production, which decreases LEE expression, would decrease RAJ colonization by EHEC, cattle were challenged at the RAJ with WT oryenI+EHEC. Although theyenI+EHEC colonized the RAJ with efficiency equal to that of the WT, there was a trend for the cattle to shed the WT strain longer than theyenI+EHEC.

scholarly journals Ethanolamine Controls Expression of Genes Encoding Components Involved in Interkingdom Signaling and Virulence in Enterohemorrhagic Escherichia coli O157:H7

mBio ◽  
2012 ◽  
Vol 3 (3) ◽  
Author(s):  
Melissa M. Kendall ◽  
Charley C. Gruber ◽  
Christopher T. Parker ◽  
Vanessa Sperandio
Keyword(s):  
Gene Expression ◽  
Escherichia Coli ◽  
Cell Signaling ◽  
Nitrogen Source ◽  
Virulence Genes ◽  
Virulence Gene ◽  
Human Pathogen ◽  
Signaling Molecule ◽  
Content Type ◽  
Virulence Gene Expression

ABSTRACTBacterial pathogens must be able to both recognize suitable niches within the host for colonization and successfully compete with commensal flora for nutrients in order to establish infection. Ethanolamine (EA) is a major component of mammalian and bacterial membranes and is used by pathogens as a carbon and/or nitrogen source in the gastrointestinal tract. The deadly human pathogen enterohemorrhagicEscherichia coliO157:H7 (EHEC) uses EA in the intestine as a nitrogen source as a competitive advantage for colonization over the microbial flora. Here we show that EA is not only important for nitrogen metabolism but that it is also used as a signaling molecule in cell-to-cell signaling to activate virulence gene expression in EHEC. EA in concentrations that cannot promote growth as a nitrogen source can activate expression of EHEC’s repertoire of virulence genes. The EutR transcription factor, known to be the receptor of EA, is only partially responsible for this regulation, suggesting that yet another EA receptor exists. This important link of EA with metabolism, cell-to-cell signaling, and pathogenesis, highlights the fact that a fundamental means of communication within microbial communities relies on energy production and processing of metabolites. Here we show for the first time that bacterial pathogens not only exploit EA as a metabolite but also coopt EA as a signaling molecule to recognize the gastrointestinal environment and promote virulence expression.IMPORTANCEIn order to successfully cause disease, a pathogen must be able to sense a host environment and modulate expression of its virulence genes as well as compete with the indigenous microbiota for nutrients. Ethanolamine (EA) is present in the large intestine due to the turnover of intestinal cells. Here, we show that the human pathogenEscherichia coliO157:H7, which causes bloody diarrhea and hemolytic-uremic syndrome, regulates virulence gene expression through EA metabolism and by responding to EA as a signal. These findings provide the first information directly linking EA with bacterial pathogenesis.

scholarly journals Phosphotyrosine-Mediated Regulation of Enterohemorrhagic Escherichia coli Virulence

mBio ◽  
2018 ◽  
Vol 9 (1) ◽  
Author(s):  
Colin D. Robertson ◽  
Tracy H. Hazen ◽  
James B. Kaper ◽  
David A. Rasko ◽  
Anne-Marie Hansen
Keyword(s):  
Gene Expression ◽  
Escherichia Coli ◽  
Dna Binding ◽  
Tyrosine Phosphorylation ◽  
Virulence Gene ◽  
Enterohemorrhagic Escherichia Coli ◽  
Environmental Cues ◽  
Virulence Gene Expression ◽  
Phosphotyrosine Signaling ◽  
Fine Tune

ABSTRACTEnteric pathogens with low infectious doses rely on the ability to orchestrate the expression of virulence and metabolism-associated genes in response to environmental cues for successful infection. Accordingly, the human pathogen enterohemorrhagicEscherichia coli(EHEC) employs a complex multifaceted regulatory network to link the expression of type III secretion system (T3SS) components to nutrient availability. While phosphorylation of histidine and aspartate residues on two-component system response regulators is recognized as an integral part of bacterial signaling, the involvement of phosphotyrosine-mediated control is minimally explored in Gram-negative pathogens. Our recent phosphotyrosine profiling study ofE. coliidentified 342 phosphorylated proteins, indicating that phosphotyrosine modifications in bacteria are more prevalent than previously anticipated. The present study demonstrates that tyrosine phosphorylation of a metabolite-responsive LacI/GalR family regulator, Cra, negatively affects T3SS expression under glycolytic conditions that are typical for the colonic lumen environment where production of the T3SS is unnecessary. Our data suggest that Cra phosphorylation affects T3SS expression by modulating the expression ofler, which encodes the major activator of EHEC virulence gene expression. Phosphorylation of the Cra Y47 residue diminishes DNA binding to fine-tune the expression of virulence-associated genes, including those of the locus of enterocyte effacement pathogenicity island that encode the T3SS, and thereby negatively affects the formation of attaching and effacing lesions. Our data indicate that tyrosine phosphorylation provides an additional mechanism to control the DNA binding of Cra and other LacI/GalR family regulators, including LacI and PurR. This study describes an initial effort to unravel the role of global phosphotyrosine signaling in the control of EHEC virulence potential.IMPORTANCEEnterohemorrhagicEscherichia coli(EHEC) causes outbreaks of hemorrhagic colitis and the potentially fatal hemolytic-uremic syndrome. Successful host colonization by EHEC relies on the ability to coordinate the expression of virulence factors in response to environmental cues. A complex network that integrates environmental signals at multiple regulatory levels tightly controls virulence gene expression. We demonstrate that EHEC utilizes a previously uncharacterized phosphotyrosine signaling pathway through Cra to fine-tune the expression of virulence-associated genes to effectively control T3SS production. This study demonstrates that tyrosine phosphorylation negatively affects the DNA-binding capacity of Cra, which affects the expression of genes related to virulence and metabolism. We demonstrate for the first time that phosphotyrosine-mediated control affects global transcription in EHEC. Our data provide insight into a hitherto unexplored regulatory level of the global network controlling EHEC virulence gene expression.

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