Helicobacter and Salmonella Persistent Infection Strategies

Monack, Denise M.

doi:10.1101/cshperspect.a010348

Cited by 39 publications

(29 citation statements)

References 166 publications

(195 reference statements)

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“…In contrast, two independent but similar challenge experiments with S. Typhimurium showed no protective effect of the probiotic E. faecium NCIMB 10415 on pathogen shedding in weaned pigs (Szabo et al 2009;Kreuzer et al 2012). An explanation could be that Salmonella has evolved manifold strategies to evade or down-regulate the host immune system and spread beyond intestinal boundaries (Monack, 2013). In this context, it could be possible that -despite the protective effect against pathogenic E. coli -some immunomodulating properties of E. faecium NCIMB 10415 in pigs could cause a disadvantage for the host upon challenge with Salmonella.…”

Section: Prevention Of Diarrheamentioning

confidence: 99%

Immunomodulating effects of probiotics for microbiota modulation, gut health and disease resistance in pigs

Roselli

Pieper

Rogel–Gaillard

et al. 2017

Animal Feed Science and Technology

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General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/pure/about/ebr-terms HIGHLIGHTS-Updated literature overview about probiotics, prebiotics and synbiotics on pig gut health is provided -Both in vivo studies performed in pigs and in vitro studies conducted in pig intestinal cell lines are described -A critical outcome of the described results is provided -The concept of "proxy measurements" for pig gut health is widely discussed -The link between gut microbiota and mucsal immune system is described Abstract:Probiotics are live microorganisms that can confer a health benefit on the host, and amongst various mechanisms probiotics are believed to exert their effects by production of antimicrobial substances, competition with pathogens for adhesion sites and nutrients, enhancement of mucosal barrier integrity and immune modulation. Through these activities probiotics can support three core benefits for the host: supporting a healthy gut microbiota, a healthy digestive tract and a healthy immune system. More recently, the concept of combining probiotics and prebiotics, i.e. synbiotics, for the beneficial effect on gut health of pigs has attracted major interest, and examples of probiotic and prebiotic benefits for pigs are pathogen inhibition and immunomodulation. Yet, it remains to be defined in pigs, what exactly is a healthy gut. Because of the high level of variability in growth and feed conversion between individual pigs in commercial production systems, measuring the impact of probiotics on gut health defined by improvements in overall productivity requires large experiments. For this reason, many studies have concentrated on measuring the effects of the feed additives on proxies of gut health including many immunological measures, in more controlled experiments. With the major focus of studying the balance between gut microbiology, immunology and physiology, and the potential for prevention of intestinal disorders in pigs, we therefore performed a literature review of the immunomodulatory effects of probiotics, either alone or in combination with prebiotics, based on in vivo, in vitro and ex vivo porcine experiments. A 3 consistent number of studies showed the potential capacity in terms of immunomodulatory activities of these feed additives in pigs, but contrasting results can also be obtained from the literature.Reasons for this are not clear but could be related to differences with respect to the probiotic strain used, experimental settings, diets, initial microbiota colonization, administration route, time and frequency of administration of the probiotic strain and sampling for analysis. Hence, the use of proxy measurements of enteric health based on observable immunological parameters presents significant problems at the moment, and cannot be considered robust, reliable predictors of the probiotic activity in vivo, in relation to pig gut health. In c...

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Section: Prevention Of Diarrheamentioning

confidence: 99%

Immunomodulating effects of probiotics for microbiota modulation, gut health and disease resistance in pigs

Roselli

Pieper

Rogel–Gaillard

et al. 2017

Animal Feed Science and Technology

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“…It has been clearly established that motility is a critical virulence factor for H. pylori infections (9)(10)(11)(12)(13). This motility, observed under conditions of elevated viscosity (as found in the gastric lumen), is due to a unipolar bundle of sheathed flagella, the structural filaments of which are composed of two flagellin protein species, FlaA and FlaB.…”

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confidence: 99%

Small-Molecule Inhibitors of the Pseudaminic Acid Biosynthetic Pathway: Targeting Motility as a Key Bacterial Virulence Factor

Ménard

Schoenhofen

Lin

et al. 2014

Antimicrob Agents Chemother

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Helicobacter pylori is motile by means of polar flagella, and this motility has been shown to play a critical role in pathogenicity. The major structural flagellin proteins have been shown to be glycosylated with the nonulosonate sugar, pseudaminic acid (Pse). This glycan is unique to microorganisms, and the process of flagellin glycosylation is required for H. pylori flagellar assembly and consequent motility. As such, the Pse biosynthetic pathway offers considerable potential as an antivirulence drug target, especially since motility is required for H. pylori colonization and persistence in the host. This report describes screening the five Pse biosynthetic enzymes for small-molecule inhibitors using both high-throughput screening (HTS) and in silico (virtual screening [VS]) approaches. Using a 100,000-compound library, 1,773 hits that exhibited a 40% threshold inhibition at a 10 M concentration were identified by HTS. In addition, VS efforts using a 1.6-million compound library directed at two pathway enzymes identified 80 hits, 4 of which exhibited reasonable inhibition at a 10 M concentration in vitro. Further secondary screening which identified 320 unique molecular structures or validated hits was performed. Following kinetic studies and structureactivity relationship (SAR) analysis of selected inhibitors from our refined list of 320 compounds, we demonstrated that three inhibitors with 50% inhibitory concentrations (IC 50 s) of approximately 14 M, which belonged to a distinct chemical cluster, were able to penetrate the Gram-negative cell membrane and prevent formation of flagella.

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“…Out of these, ChePep is preferentially found on the polar region of the flagella and regulates flagellar rotation, which is an important phenomenon for the movement of the H. pylori. 40,41 Many mutational studies of these chemotaxis proteins suggested a defect in sensing low pH, thereby, a defect in their ability in colonization. 42 In case of ChePep mutant strains, which colonize on the mucus layer similar to wild-type strains, ΔChePep mutant is not colonized in the glandular region, which needs the bacterial movement.…”

Section: Chemotaxis Is Important For Persistent Colonizationmentioning

confidence: 99%

“…Proteins like CheA, CheW, CheY, and ChePep are mainly responsible proteins for chemotactic properties in the bacterium. Out of these, ChePep is preferentially found on the polar region of the flagella and regulates flagellar rotation, which is an important phenomenon for the movement of the H. pylori . Many mutational studies of these chemotaxis proteins suggested a defect in sensing low pH, thereby, a defect in their ability in colonization .…”

Section: Introductionmentioning

confidence: 99%

Unraveling the factors and mechanism involved in persistence: Host‐pathogen interactions in Helicobacter pylori

Gupta

Maurya

Verma

et al. 2019

J of Cellular Biochemistry

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Helicobacter pylori and humans have one of the most complex relationships in nature. How a bacterium manages to live in one of the harshest and hostile environments is a topic of unraveling mysteries. H. pylori is a prevalent species and it colonizes the human gut of more than 50% of the world population. It infects the epithelial region of antrum and persists there for a long period. Over the time of evolution, H. pylori has developed complex strategies to extend the degree of inflammation in gastric mucosa. H. pylori needs specific adaptations for initial colonization into the host environment like helical shape, flagellar movement, chemotaxis, and the production of urease enzyme that neutralizes acidic environment of the stomach. There are several factors from the bacterium as well as from the host that participate in these complex interactions. On the other hand, to establish the persistent infection, H. pylori escapes the immune system by mimicking the host antigens. This pathogen has the ability to dodge the immune system and then persist there in the form of host cell, which leads to immune tolerance. H. pylori has an ability to manipulate its own pathogen‐associated molecular patterns, which leads to an inhibition in the binding with specific pattern recognition receptors of the host to avoid immune cell detection. Also, it manipulates the host metabolic homeostasis in the gastric epithelium. Besides, it has several genes, which may get involved in the acquisition of nutrition from the host to survive longer in the host. Due to the persistence of H. pylori, it causes chronic inflammation and raises the chances of gastric cancer. This review highlights the important elements, which are certainly responsible for the persistence of H. pylori in the human host.

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Helicobacter and Salmonella Persistent Infection Strategies

Cited by 39 publications

References 166 publications

Immunomodulating effects of probiotics for microbiota modulation, gut health and disease resistance in pigs

Immunomodulating effects of probiotics for microbiota modulation, gut health and disease resistance in pigs

Small-Molecule Inhibitors of the Pseudaminic Acid Biosynthetic Pathway: Targeting Motility as a Key Bacterial Virulence Factor

Unraveling the factors and mechanism involved in persistence: Host‐pathogen interactions in Helicobacter pylori

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