Expression of Colonization Factor CS5 of Enterotoxigenic Escherichia coli (ETEC) Is Enhanced In Vivo and by the Bile Component Na Glycocholate Hydrate

Nicklasson, Matilda; Sjöling, Åsa; Mentzer, Astrid von; Qadri, Firdausi; Svennerholm, Ann‐Mari

doi:10.1371/journal.pone.0035827

Cited by 37 publications

(35 citation statements)

References 40 publications

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“…We agree constitutive expression of these adherence factors would possibly interfere with the pathogenic lifestyle of Shigella and impair critical immune evasion tactics. Similar regulation of adhesion genes has been described for other bacterial pathogens such as enterotoxigenic, enterohemorrhagic, and uropathogenic E. coli (70–74). Clearly human-adapted pathogens have efficiently evolved to regulate virulence gene expression for efficient colonization and infection tactics in the human host.…”

Section: Discussionsupporting

confidence: 66%

Shigella flexneri adherence factor expression in in vivo-like conditions

Chanin

Nickerson

Llanos-Chea

et al. 2019

Preprint

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26The Shigella species are Gram-negative, facultative intracellular pathogens that invade the 27 colonic epithelium and cause significant diarrheal disease. Despite extensive research on the pathogen, 28 comprehensive understanding of how Shigella initiates contact with epithelial cells remains unknown. 29 Shigella maintains many of the same Escherichia coli adherence gene operons; however, at least one 30 critical gene component in each operon is currently annotated as a pseudogene in reference genomes. 31 These annotations, coupled with a lack of structures upon microscopic analysis following growth in 32 laboratory media, have led the field to hypothesize that Shigella is unable to produce fimbriae or other 33 "traditional" adherence factors. Nevertheless, our previous analyses have demonstrated that a 34 combination of bile salts and glucose induce both biofilm formation and adherence to colonic epithelial 35 cells. Through a two-part investigation, we first utilized various transcriptomic analyses to demonstrate 36 that S. flexneri strain 2457T adherence gene operons are transcribed. Subsequently, we performed 37 mutation, electron microscopy, biofilm, infection, and proteomic analyses to characterize three of the 38 structural genes. In combination, these studies demonstrate that despite the gene annotations, S. 39 flexneri 2457T uses adherence factors to initiate biofilm formation as well as epithelial cell contact. 40 Furthermore, host factors, namely glucose and bile salts in the small intestine, offer key environmental 41 stimuli required for proper adherence factor expression in S. flexneri. This research may have a 42 significant impact on vaccine development for Shigella and further highlights the importance of 43 utilizing in vivo-like conditions to study bacterial pathogenesis. 44 45 Importance 46 Bacterial pathogens have evolved to regulate virulence gene expression at critical points in the 47 colonization and infection processes to successfully cause disease. The Shigella species infect the 48 epithelial cells lining the colon to result in millions of cases of diarrhea and a significant global health 49 burden. As antibiotic resistance rates increase, understanding the mechanisms of infection are vital to 50 3 ensure successful vaccine development. Despite significant gains in our understanding of Shigella 51 infection, it remains unknown how the bacteria initiate contact with the colonic epithelium. Most 52 pathogens harbor multiple adherence factors to facilitate this process, but Shigella was thought to have 53 lost the ability to produce these factors. Interestingly, we have identified conditions that mimic some 54 features of gastrointestinal transit and enable Shigella to express adherence factors. This work 55 highlights aspects of genetic regulation for Shigella adherence factors and may have a significant 56 impact on future vaccine development. 57 58 59Shigella flexneri is a Gram-negative, facultative anaerobe that infects millions of people each 60 year by causing water...

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Section: Discussionsupporting

confidence: 66%

Shigella flexneri adherence factor expression in in vivo-like conditions

Chanin

Nickerson

Llanos-Chea

et al. 2019

Preprint

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“…CS6 is a structural gene important in binding and pathogenicity of ETEC, which has two structural subunits 27 showing differential binding capacity that may be linked with pathogenicity. [28][29][30] In a study of international travelers returning to Spain, 30 of 52 (58%) of ETEC strains isolated were CS21 positive and 14 of 52 (27%) were CS6 positive. 31 A study of a killed oral vaccine combining Vibrio cholerae-binding toxin plus ETEC CFs, carried out in Mexico and Guatemala, was of limited value because it did not contain CS6 found in prevalent ETEC strains encountered in the study.…”

Section: Discussionmentioning

confidence: 99%

Colonization Factors in Enterotoxigenic Escherichia coli Strains in Travelers to Mexico, Guatemala, and India Compared with Children in Houston, Texas

Kharat¹,

Ahmed²,

Jiang³

et al. 2017

The American Society of Tropical Medicine and Hygiene

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Abstract. Enterotoxigenic Escherichia coli (ETEC) can be attributed to around 200 million diarrheal episodes and 380,000 deaths in the developing regions. Travelers' diarrhea occurs in 15-40% of travelers to developing regions with ETEC being the most important etiologic agent. This study aims to describe the distribution of enterotoxins and colonization factor (CF) profiles of ETEC isolates from stool samples of adult travelers acquiring diarrhea in Mexico, Guatemala, and India and a group of children with acute diarrhea in Houston, TX, between 2007 and 2012. The heat-labile/heat-stable (LT/ST) enterotoxins and CFs from 252 patients were determined using polymerase chain reaction assay. Among the 252 ETEC isolates, 15% were LT-only, 58% were ST-only, and 28% produced both LT and ST. The distribution of LT-only (12-15%) and ST-only (55-56%) isolates was similar between Latin American and Indian sites. The most prevalent CF was CS21, expressed in 65% of the isolates followed by CS6 (25%) and CS3 (17%). Among the international travelers, 64% of the ETEC isolates expressed CS21. CS21 was expressed in 46% of isolates from Latin America compared with 96% of isolates from India (P < 0.0001). CS21 was expressed in 85% isolates from Houston children. CS21 was increasingly found in ST-only (P = 0.003) and ST/LT (P = 0.026) ETEC compared with LT-only ETEC. High frequency of finding CS21 among recent isolates of ETEC over a wide geographic distribution warrants additional studies on this CF. Highly conserved CS21 is an important target for potential multivalent ETEC vaccines.

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“…RNA was extracted using the RNeasy minikit (Qiagen) with the addition of lysozyme and proteinase K to the lysis buffer prior to disruption of the tissues using the TissueLyser (Qiagen). The RNA was subjected to double DNase treatment to ensure that the analysis would not be confounded by DNA contamination, as described previously (38). The integrity of the resulting RNA was assessed using a BioAnalyser (Agilent) with an RNA integrity number (RIN) of Ͼ6 as a cutoff, and the RNA concentration was determined by Qubit (Invitrogen) measurement just prior to the library preparation procedure.…”

Section: Methodsmentioning

confidence: 99%

In Vivo Analysis of the Viable Microbiota and Helicobacter pylori Transcriptome in Gastric Infection and Early Stages of Carcinogenesis

et al. 2017

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Emerging evidence shows that the human microbiota plays a larger role in disease progression and health than previously anticipated. Helicobacter pylori, the causative agent of gastric cancer and duodenal and gastric ulcers, was early associated with gastric disease, but it has also been proposed that the accompanying microbiota in Helicobacter pylori-infected individuals might affect disease progression and gastric cancer development. In this study, the composition of the transcriptionally active microbial community and H. pylori gene expression were determined using metatranscriptomic RNA sequencing of stomach biopsy specimens from individuals with different H. pylori infection statuses and premalignant tissue changes. The results show that H. pylori completely dominates the microbiota not only in infected individuals but also in most individuals classified as H. pylori uninfected using conventional methods. Furthermore, H. pylori abundance is positively correlated with the presence of Campylobacter, Deinococcus, and Sulfurospirillum. Finally, we quantified the expression of a large number of Helicobacter pylori genes and found high expression of genes involved in pH regulation and nickel transport. Our study is the first to dissect the viable microbiota of the human stomach by metatranscriptomic analysis, and it shows that metatranscriptomic analysis of the gastric microbiota is feasible and can provide new insights into how bacteria respond in vivo to variations in the stomach microenvironment and at different stages of disease progression.

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Expression of Colonization Factor CS5 of Enterotoxigenic Escherichia coli (ETEC) Is Enhanced In Vivo and by the Bile Component Na Glycocholate Hydrate

Cited by 37 publications

References 40 publications

Shigella flexneri adherence factor expression in in vivo-like conditions

Shigella flexneri adherence factor expression in in vivo-like conditions

Colonization Factors in Enterotoxigenic Escherichia coli Strains in Travelers to Mexico, Guatemala, and India Compared with Children in Houston, Texas

In Vivo Analysis of the Viable Microbiota and Helicobacter pylori Transcriptome in Gastric Infection and Early Stages of Carcinogenesis

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