scholarly journals Modulation of Enterohaemorrhagic Escherichia coli Survival and Virulence in the Human Gastrointestinal Tract

2018 ◽  
Vol 6 (4) ◽  
pp. 115 ◽  
Author(s):  
Grégory Jubelin ◽  
Mickaël Desvaux ◽  
Stephanie Schüller ◽  
Lucie Etienne-Mesmin ◽  
Maite Muniesa ◽  
...  

Enterohaemorrhagic Escherichia coli (EHEC) is a major foodborne pathogen responsible for human diseases ranging from diarrhoea to life-threatening complications. Survival of the pathogen and modulation of virulence gene expression along the human gastrointestinal tract (GIT) are key features in bacterial pathogenesis, but remain poorly described, due to a paucity of relevant model systems. This review will provide an overview of the in vitro and in vivo studies investigating the effect of abiotic (e.g., gastric acid, bile, low oxygen concentration or fluid shear) and biotic (e.g., gut microbiota, short chain fatty acids or host hormones) parameters of the human gut on EHEC survival and/or virulence (especially in relation with motility, adhesion and toxin production). Despite their relevance, these studies display important limitations considering the complexity of the human digestive environment. These include the evaluation of only one single digestive parameter at a time, lack of dynamic flux and compartmentalization, and the absence of a complex human gut microbiota. In a last part of the review, we will discuss how dynamic multi-compartmental in vitro models of the human gut represent a novel platform for elucidating spatial and temporal modulation of EHEC survival and virulence along the GIT, and provide new insights into EHEC pathogenesis.

Gut ◽  
2020 ◽  
pp. gutjnl-2020-322468
Author(s):  
Xiaolong He ◽  
Jie Gao ◽  
Liang Peng ◽  
Tongtong Hu ◽  
Yu Wan ◽  
...  

ObjectiveO-linked N-acetylglucosaminylation (O-GlcNAcylation), controlled by O-GlcNAcase (OGA) and O-GlcNAc transferase (OGT), is an important post-translational modification of eukaryotic proteins and plays an essential role in regulating gut inflammation. Gut microbiota encode various enzymes involved in O-GlcNAcylation. However, the characteristics, abundance and function of these enzymes are unknown.DesignWe first investigated the structure and taxonomic distribution of bacterial OGAs and OGTs. Then, we performed metagenomic analysis to explore the OGA genes abundance in health samples and different diseases. Finally, we employed in vitro and in vivo experiments to determine the effects and mechanisms of bacterial OGAs to hydrolyse O-GlcNAcylated proteins in host cells and suppress inflammatory response in the gut.ResultsWe found OGAs, instead of OGTs, are enriched in Bacteroidetes and Firmicutes, the major bacterial divisions in the human gut. Most bacterial OGAs are secreted enzymes with the same conserved catalytic domain as human OGAs. A pooled analysis on 1999 metagenomic samples encompassed six diseases revealed that bacterial OGA genes were conserved in healthy human gut with high abundance, and reduced exclusively in ulcerative colitis. In vitro studies showed that bacterial OGAs could hydrolyse O-GlcNAcylated proteins in host cells, including O-GlcNAcylated NF-κB-p65 subunit, which is important for activating NF-κB signalling. In vivo studies demonstrated that gut bacteria-derived OGAs could protect mice from chemically induced colonic inflammation through hydrolysing O-GlcNAcylated proteins.ConclusionOur results reveal a previously unrecognised enzymatic activity by which gut microbiota influence intestinal physiology and highlight bacterial OGAs as a promising therapeutic strategy in colonic inflammation.


2019 ◽  
Author(s):  
Wenfa Ng

What biochemical tricks did Escherichia coli obtained or evolved during its time as a commensal in the human gastrointestinal system? E. coli is a natural symbiont of the human gastrointestinal tract. Thus, through evolutionary timescales, the bacterium must have co-evolved with humans with conditions in the gastrointestinal tract serving as selection pressure for the evolution of a variety of biochemical and physiological adaptations. These adaptations came about through mutations that arise in the genome, and thus, could be retrospectively profiled to understand the differing evolutionary pressure that selected for specific traits in the bacterium useful for its survival in the changing conditions of the human gut. Using sequenced and annotated genome information of different strains of E. coli as a guide and starting point, possibility exists to use a combination of bioinformatics, biochemical, and genetic approaches to decipher the biochemical tricks that E. coli evolved or pick up during its time as a commensal in the human gastrointestinal tract. Specifically, sequenced genomes serve as a molecular fossil from which we could obtain imprints of the various evolutionary events that impact on the bacterium. Adaptations to changing conditions could also be deciphered through analysis of single nucleotide polymorphism (SNPs). Comparison of the profiled mutations and altered gene sequences between different E. coli strains with different co-evolutionary history with the human gut might help reveal the different length of time in which different E. coli strains have co-evolved with humans. More importantly, multiple sequence alignment and phylogenetic analysis could also reveal which genes first evolve due to selection pressure exerted on the bacterium by fluctuating environmental conditions in the human gut. Genetic knockdowns of the putative genes would help indicate the overall essentiality of the genes to the physiology and functioning of the modern E. coli bacterium. The approach outlined should help answer some of the most fundamental questions regarding the evolution of different E. coli strains as well as how natural selection exerts its influence on the physiology of a commensal organism with respect to host adaptation.


2021 ◽  
Vol 12 ◽  
Author(s):  
Baiyuan Li ◽  
Huahai Chen ◽  
Linyan Cao ◽  
Yunfei Hu ◽  
Dan Chen ◽  
...  

A stable intestinal microflora is an essential prerequisite for human health. This study investigated the interaction between Escherichia coli exopolysaccharides (named EPS-m2) and the human gut microbiota (HGM) in vitro. The EPS-m2 was produced by E. coli WM3064 when treated with ceftriaxone. The monosaccharide composition analysis revealed that EPS-m2 is composed of glucuronic acid, glucose, fucose, galactose/N-acetyl glucosamine, arabinose, xylose, and ribose with a molar ratio of approximately 77:44:29:28:2:1:1. The carbohydrates, protein, and uronic acids contents in EPS-m2 was 78.6 ± 0.1%, 4.38 ± 0.11%, and 3.86 ± 0.09%, respectively. In vitro batch fermentation experiments showed that 77% of EPS-m2 could be degraded by human fecal microbiota after 72 h of fermentation. In reverse, 16S rRNA gene sequencing analysis showed that EPS-m2 increased the abundance of Alistipes, Acinetobacter, Alloprevotella, Howardella, and Oxalobacter; GC detection illustrated that EPS-m2 enhanced the production of SCFAs. These findings indicated that EPS-m2 supplementation could regulate the HGM and might facilitate modulation of human health.


2019 ◽  
Author(s):  
Wenfa Ng

What biochemical tricks did Escherichia coli obtained or evolved during its time as a commensal in the human gastrointestinal system? E. coli is a natural symbiont of the human gastrointestinal tract. Thus, through evolutionary timescales, the bacterium must have co-evolved with humans with conditions in the gastrointestinal tract serving as selection pressure for the evolution of a variety of biochemical and physiological adaptations. These adaptations came about through mutations that arise in the genome, and thus, could be retrospectively profiled to understand the differing evolutionary pressure that selected for specific traits in the bacterium useful for its survival in the changing conditions of the human gut. Using sequenced and annotated genome information of different strains of E. coli as a guide and starting point, possibility exists to use a combination of bioinformatics, biochemical, and genetic approaches to decipher the biochemical tricks that E. coli evolved or pick up during its time as a commensal in the human gastrointestinal tract. Specifically, sequenced genomes serve as a molecular fossil from which we could obtain imprints of the various evolutionary events that impact on the bacterium. Adaptations to changing conditions could also be deciphered through analysis of single nucleotide polymorphism (SNPs). Comparison of the profiled mutations and altered gene sequences between different E. coli strains with different co-evolutionary history with the human gut might help reveal the different length of time in which different E. coli strains have co-evolved with humans. More importantly, multiple sequence alignment and phylogenetic analysis could also reveal which genes first evolve due to selection pressure exerted on the bacterium by fluctuating environmental conditions in the human gut. Genetic knockdowns of the putative genes would help indicate the overall essentiality of the genes to the physiology and functioning of the modern E. coli bacterium. The approach outlined should help answer some of the most fundamental questions regarding the evolution of different E. coli strains as well as how natural selection exerts its influence on the physiology of a commensal organism with respect to host adaptation.


2015 ◽  
Vol 3 (4) ◽  
pp. 725-745 ◽  
Author(s):  
Charlotte Cordonnier ◽  
Jonathan Thévenot ◽  
Lucie Etienne-Mesmin ◽  
Sylvain Denis ◽  
Monique Alric ◽  
...  

Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381
Author(s):  
EM Pferschy-Wenzig ◽  
K Koskinen ◽  
C Moissl-Eichinger ◽  
R Bauer

2017 ◽  
Author(s):  
EM Pferschy-Wenzig ◽  
A Roßmann ◽  
K Koskinen ◽  
H Abdel-Aziz ◽  
C Moissl-Eichinger ◽  
...  

Fermentation ◽  
2021 ◽  
Vol 7 (1) ◽  
pp. 14
Author(s):  
Nelson Mota de Carvalho ◽  
Diana Luazi Oliveira ◽  
Mayra Anton Dib Saleh ◽  
Manuela Pintado ◽  
Ana Raquel Madureira

The use of fecal inoculums for in vitro fermentation models requires a viable gut microbiota, capable of fermenting the unabsorbed nutrients. Fresh samples from human donors are used; however, the availability of fresh fecal inoculum and its inherent variability is often a problem. This study aimed to optimize a method of preserving pooled human fecal samples for in vitro fermentation studies. Different conditions and times of storage at −20 °C were tested. In vitro fermentation experiments were carried out for both fresh and frozen inoculums, and the metabolic profile compared. In comparison with the fresh, the inoculum frozen in a PBS and 30% glycerol solution, had a significantly lower (p < 0.05) bacterial count (<1 log CFU/mL). However, no significant differences (p < 0.05) were found between the metabolic profiles after 48 h. Hence, a PBS and 30% glycerol solution can be used to maintain the gut microbiota viability during storage at −20 °C for at least 3 months, without interfering with the normal course of colonic fermentation.


2021 ◽  
Author(s):  
Shiyi Lu ◽  
Deirdre Mikkelsen ◽  
Hong Yao ◽  
Barbara Williams ◽  
Bernadine Flanagan ◽  
...  

Plant cell walls as well as their component polysaccharides in foods can be utilized to alter and maintain a beneficial human gut microbiota, but it is not known whether the...


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