Transcriptional Modulation of Enterotoxigenic Escherichia coli Virulence Genes in Response to Epithelial Cell Interactions

Kansal, Rita G.; Rasko, David A.; Sahl, Jason W.; Munson, George P.; Roy, Koushik; Luo, Qingwei; Sheikh, Alaullah; Kuhne, Kurt; Fleckenstein, James M.

doi:10.1128/iai.00919-12

Cited by 60 publications

(59 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…More recent attempts to identify novel vaccine candidates by investigation of antigens that are transcriptionally modulated during pathogen-host interactions also highlighted eaeH, since it was strongly upregulated after contact of ETEC with intestinal epithelial cells (21). The results presented here reaffirm these findings and demonstrate the expression of EaeH by a variety of other ETEC strains.…”

Section: Discussionsupporting

confidence: 78%

“…Earlier transcriptome studies demonstrated that eaeH expression is increased following epithelial cell contact (21). Accordingly, we found that shortly after attachment to host cells (5 min, Fig.…”

Section: Eaeh Encodes a Surface Molecule With Features Shared By Bactsupporting

confidence: 48%

“…One gene, eaeH, which was strongly upregulated upon epithelial cell attachment, was originally identified in ETEC by subtractive hybridization with a laboratory strain of E. coli (33). Although our earlier studies suggested that eaeH encodes a surface-expressed antigen that is expressed in the context of epithelial cells (21), its role in the pathogenesis of ETEC has not been explored. The present studies were undertaken to examine the role of this highly conserved antigen in ETEC bacterium-host interaction and toxin delivery.…”

mentioning

confidence: 99%

“…More recent investigations have highlighted a number of novel putative virulence factors (16,17), unique interactions of ETEC with the epithelium (18)(19)(20), and an intricate orchestration of multiple pathogen-host events (21) that culminate in successful toxin delivery to epithelial cell targets (22). Collectively, the emerging data suggest that these sophisticated interactions of ETEC strains with their host might be exploited in outlining novel strategies for vaccine development (23).…”

mentioning

confidence: 99%

“…Therefore, over time it has become apparent that additional strategies are needed to complement a CF-based approach to ETEC vaccines. Interestingly, recent studies of ETEC transcriptional modulation following interaction with epithelial cells highlighted a number of genes potentially encoding novel target antigens (21). One gene, eaeH, which was strongly upregulated upon epithelial cell attachment, was originally identified in ETEC by subtractive hybridization with a laboratory strain of E. coli (33).…”

mentioning

confidence: 99%

See 4 more Smart Citations

Contribution of the Highly Conserved EaeH Surface Protein to Enterotoxigenic Escherichia coli Pathogenesis

Sheikh

Luo

Roy³

et al. 2014

Infect Immun

Self Cite

View full text Add to dashboard Cite

f Enterotoxigenic Escherichia coli (ETEC) strains are among the most common causes of diarrheal illness worldwide. These pathogens disproportionately afflict children in developing countries, where they cause substantial morbidity and are responsible for hundreds of thousands of deaths each year. Although these organisms are important targets for enteric vaccines, most development efforts to date have centered on a subset of plasmid-encoded fimbrial adhesins known as colonization factors and heatlabile toxin (LT). Emerging data suggest that ETEC undergoes considerable changes in its surface architecture, sequentially deploying a number of putative adhesins during its interactions with the host. We demonstrate here that one putative highly conserved, chromosomally encoded adhesin, EaeH, engages the surfaces of intestinal epithelial cells and contributes to bacterial adhesion, LT delivery, and colonization of the small intestine. Infectious diarrhea continues to cause tremendous suffering in developing countries, resulting in an estimated one to two million deaths each year. Enterotoxigenic Escherichia coli (ETEC) contributes significantly to premature deaths from diarrheal illness in young children (1, 2) and causes substantial morbidity in surviving children and adults (3). ETEC strains are perennially the leading etiology of diarrhea in travelers to areas where ETEC strains are endemic (4).By definition, these organisms secrete heat-labile (LT) and/or heat-stable (ST) enterotoxins that induce host cell production of cyclic nucleotides (cyclic AMP [cAMP] and cGMP, respectively) to activate protein kinases that ultimately result in phosphorylation of the cystic fibrosis transmembrane regulatory channel (CFTR) (5-7) and Na ϩ ion exchangers (8) on the surfaces of intestinal epithelial cells. Ensuing chloride secretion through CFTR, as well as the commensurate loss of salt and water into the intestinal lumen, results in the cholera-like watery diarrhea characteristic of ETEC infections (9).In the current paradigm for ETEC pathogenesis, this organism must effectively colonize the small intestine to deliver LT and/or ST efficiently. The majority of pathogenesis (10-12) and molecular epidemiology (13) studies, as well as subsequent vaccine development efforts (14, 15), have focused primarily on plasmid-encoded fimbrial colonization factors (CFs), which are felt to be critical for colonization of the small intestine.This longstanding but fairly simple view of ETEC pathogenesis in which bacteria adhere via CFs to the small intestine, where these pathogens release their toxin(s), likely underestimates the complexity of these pathogens. More recent investigations have highlighted a number of novel putative virulence factors (16, 17), unique interactions of ETEC with the epithelium (18)(19)(20), and an intricate orchestration of multiple pathogen-host events (21) that culminate in successful toxin delivery to epithelial cell targets (22). Collectively, the emerging data suggest that these sophisticated interactions of ETEC ...

show abstract

Section: Discussionsupporting

confidence: 78%

Section: Eaeh Encodes a Surface Molecule With Features Shared By Bactsupporting

confidence: 48%

mentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Contribution of the Highly Conserved EaeH Surface Protein to Enterotoxigenic Escherichia coli Pathogenesis

Sheikh

Luo

Roy³

et al. 2014

Infect Immun

Self Cite

View full text Add to dashboard Cite

show abstract

Burkholderia cenocepacia–host cell contact controls the transcription activity of the trimeric autotransporter adhesin BCAM2418 gene

2020

View full text Add to dashboard Cite

Cell‐to‐cell early contact between pathogens and their host cells is required for the establishment of many infections. Among various surface factors produced by bacteria that allow an organism to become established in a host, the class of adhesins is a primary determinant. Burkholderia cenocepacia adheres to the respiratory epithelium of cystic fibrosis patients and causes chronic inflammation and disease. Cell‐to‐cell contacts are promoted by various kinds of adhesins, including trimeric autotransporter adhesins (TAAs). We observed that among the 7 TAA genes found in the B. cenocepacia K56‐2 genome, two of them (BCAM2418 and BCAS0236) express higher levels of mRNA following physical contact with host cells. Further analysis revealed that the B. cenocepacia K56‐2 BCAM2418 gene shows an on–off switch after an initial colonization period, exhibits a strong expression dependent on the host cell type, and enhances its function on cell adhesion. Furthermore, our analysis revealed that adhesion to mucin‐coated surfaces dramatically increases the expression levels of BCAM2418. Abrogation of mucin O‐glycans turns BCAM2418 gene expression off and impairs bacterial adherence. Overall, our findings suggest that glycosylated extracellular components of host membrane might be a binding site for B. cenocepacia and a signal for the differential expression of the TAA gene BCAM2418.

show abstract

Cyclic‐di‐GMP regulation of virulence in bacterial pathogens

Hall

Lee

2017

WIREs RNA

View full text Add to dashboard Cite

Signaling pathways allow bacteria to adapt to changing environments. For pathogenic bacteria, signaling pathways allow for timely expression of virulence factors and the repression of antivirulence factors within the mammalian host. As the bacteria exit the mammalian host, signaling pathways enable the expression of factors promoting survival in the environment and/or nonmammalian hosts. One such signaling pathway uses the dinucleotide cyclic-di-GMP (c-di-GMP), and many bacterial genomes encode numerous proteins that are responsible for synthesizing and degrading c-di-GMP. Once made, c-di-GMP binds to individual protein and RNA receptors to allosterically alter the macromolecule function to drive phenotypic changes. Each bacterial genome encodes unique sets of genes for c-di-GMP signaling and virulence factors so the regulation by c-di-GMP is organism specific. Recent works have pointed to evidence that c-di-GMP regulates virulence in different bacterial pathogens of mammalian hosts. In this review, we discuss the criteria for determining the contribution of signaling nucleotides to pathogenesis using a well-characterized signaling nucleotide, cyclic AMP (cAMP), in Pseudomonas aeruginosa. Using these criteria, we review the roles of c-di-GMP in mediating virulence and highlight common themes that exist among eight diverse pathogens that cause different diseases through different routes of infection and transmission. © 2017 Wiley Periodicals, Inc. How to cite this article:WIREs RNA 2018, 9:e1454. doi: 10.1002/wrna.1454 INTRODUCTIONB is-(3 0 -5 0 )-cyclic dimeric guanosine monophosphate (c-di-GMP) is a widely utilized signaling pathway that regulates bacterial adaptation to different environments. 1 C-di-GMP is synthesized from two GTP by diguanylate cyclases (DGCs) that contain a GGDEF domain and degraded into pGpG by phosphodiesterases (PDE-As) that contain EAL or HD-GYP domain. Signaling by c-di-GMP is completed when pGpG is degraded further to GMP by oligoribonuclease and related RNA degradation enzymes. [2][3][4] Thus, c-di-GMP represents one of the shortest signaling ribonucleotides. In addition, a number of genes can encode proteins with both GGDEF and EAL domains (GGDEF-EAL), indicating that levels of c-di-GMP in the cell are regulated by a complicated number of synthetic and degradative enzymes. Once made, c-di-GMP binds a diverse set of protein receptors and RNA riboswitches. 1 C-di-GMP binding to molecular receptors allosterically alters their function and downstream cellular phenotypes. 5 Genes encoding c-di-GMP signaling components are found in a large number of bacterial pathogens. This review seeks to cover the contribution of c-di-GMP signaling to bacterial pathogenesis for a number of different pathogens to identify common themes. For this review, virulence and pathogenesis is considered as the ability of the bacteria to replicate and cause disease symptoms in the mammalian host. Owing to space limitation, for each pathogen, we have referenced reviews that cover their virulence factors and their c...

show abstract

Transcriptional Modulation of Enterotoxigenic Escherichia coli Virulence Genes in Response to Epithelial Cell Interactions

Cited by 60 publications

References 62 publications

Contribution of the Highly Conserved EaeH Surface Protein to Enterotoxigenic Escherichia coli Pathogenesis

Contribution of the Highly Conserved EaeH Surface Protein to Enterotoxigenic Escherichia coli Pathogenesis

Burkholderia cenocepacia–host cell contact controls the transcription activity of the trimeric autotransporter adhesin BCAM2418 gene

Cyclic‐di‐GMP regulation of virulence in bacterial pathogens

Contact Info

Product

Resources

About