The Serotonin Neurotransmitter Modulates Virulence of Enteric Pathogens

Kumar, Aman; Russell, Regan M.; Pifer, Reed; Menezes‐Garcia, Zélia; Cuesta, Santiago; Narayanan, Sanjeev; MacMillan, John B.; Sperandio, Vanessa

doi:10.1016/j.chom.2020.05.004

Cited by 81 publications

(66 citation statements)

References 67 publications

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“…Serotonin levels have also been reported to increase when an infection is taking place; this increase is associated with the eradication of the disease via multiple pathways [35,36]. We also observed a significant increase in NE, which other studies have associated to Th2 polarization and M2 macrophage differentiation as well as an increase in nitric oxide (NO) production) [37][38][39].…”

Section: Discussionsupporting

confidence: 62%

Sexual Dimorphism of the Neuroimmunoendocrine Response in the Spleen During a Helminth Infection: A New Role for an Old Player?

Ke¹,

Pavón²,

Le³

et al. 2021

Preprint

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The interaction of the nervous, immune, and endocrine systems is crucial in the maintenance of homeostasis in vertebrates, and vital in mammals. The spleen is a key organ that regulates the neuroimmunoendocrine system. The Taenia crassiceps mouse system is an excellent experimental model to study the complex host-parasite relationship, particularly sex-associated susceptibility to infection. The aim of the present study was to determine the changes in neurotransmitters, cytokines, sex steroids, and sex-steroid receptors in the spleen of cysticercus-infected male and female mice, and the association of these different components with whole parasite counts. We found that parasite load was higher in female in comparison to male mice. The levels of the neurotransmitter epinephrine were significantly decreased in infected male animals. The expression of IL-2 and IL-4 in the spleen was markedly increased in infected mice; however, the expression of Interleukin (IL)-10 and Interferon (IFN)-γ decreased. We also observed sex-associated differences between non-infected and infected mice. Interestingly, the data show that estradiol levels increased in infected males but decreased in females. Our studies provide evidence that infection leads to changes on neuroimmunoendocrine molecules in the spleen during infection. These changes are dimorphic and impact the establishment, growth, and reproduction of T. crassiceps. Our findings support the key role of the neuroimmune network in determining sex-associated susceptibility to the helminth parasite.

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Section: Discussionsupporting

confidence: 62%

Sexual Dimorphism of the Neuroimmunoendocrine Response in the Spleen During a Helminth Infection: A New Role for an Old Player?

Ke¹,

Pavón²,

Le³

et al. 2021

Preprint

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“…The conformational change of the membrane histidine kinase delivers the phosphate to the aspartic residue on the RR to activate a domain that modulates gene expression ( 32 ). Previous studies have identified several TCSs that are essential for the virulence of O157 ( 33 ). For example, CpxA/CpxR TCS senses the neurotransmitter, serotonin, and downregulates O157 LEE gene expression ( 33 ).…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies have identified several TCSs that are essential for the virulence of O157 ( 33 ). For example, CpxA/CpxR TCS senses the neurotransmitter, serotonin, and downregulates O157 LEE gene expression ( 33 ). FusK/R TCS senses fucose produced by the commensal Bacteroides thetaiotaomicron to promote O157 colonization ( 34 ).…”

Section: Introductionmentioning

confidence: 99%

A Novel Small RNA Promotes Motility and Virulence of Enterohemorrhagic Escherichia coli O157:H7 in Response to Ammonium

Jia

Liu

et al. 2021

mBio

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Enterohemorrhagic Escherichia coli serotype O157:H7 (O157) is a critical, foodborne, human intestinal pathogen that causes severe acute hemorrhagic diarrhea, abdominal cramping, and even death. Small RNAs (sRNAs) are noncoding regulatory molecules that sense environmental changes and trigger various virulence-related signaling pathways; however, few such sRNAs have been identified in O157. Here, we report a novel sRNA, EsrF that senses high ammonium concentrations in the colon and enhances O157 pathogenicity by promoting bacterial motility and adhesion to host cells. Specifically, EsrF was found to directly interact with the 5′ untranslated regions of the flagellar biosynthetic gene, flhB, mRNA and increase its abundance, thereby upregulating expression of essential flagellar genes, including flhD, flhC, fliA, and fliC, leading to elevated O157 motility and virulence. Meanwhile, an infant rabbit model of O157 infection showed that deletion of esrF and flhB significantly attenuates O157 pathogenicity. Furthermore, NtrC—the response regulator of the NtrC/B two-component system—was found to exert direct, negative regulation of esrF expression. Meanwhile, high ammonium concentrations in the colon release the inhibitory effect of NtrC on esrF, thereby enhancing its expression and subsequently promoting bacterial colonization in the host colon. Our work reveals a novel, sRNA-centered, virulence-related signaling pathway in O157 that senses high ammonium concentrations. These findings provide novel insights for future research on O157 pathogenesis and targeted treatment strategies. IMPORTANCE The process by which bacteria sense environmental cues to regulate their virulence is complex. Several studies have focused on regulating the expression of the locus of enterocyte effacement pathogenicity island in the typical gut pathogenic bacterium, O157. However, few investigations have addressed the regulation of other virulence factors in response to intestinal signals. In this study, we report our discovery of a novel O157 sRNA, EsrF, and demonstrate that it contributed to bacterial motility and virulence in vitro and in vivo through the regulation of bacterial flagellar synthesis. Furthermore, we show that high ammonium concentrations in the colon induced esrF expression to promote bacterial virulence by releasing the repression of esrF by NtrC. This study highlights the importance of sRNA in regulating the motility and pathogenicity of O157.

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“…In this context, it is of high interest to evaluate how bacteria can respond to changes in the gut environment due to sudden increase of 5HT. In the literature, data on the biological effects of this molecule on prokaryotes are scarce in comparison with other hormones (i.e., epinephrine and NE), and most reports concern only pathogenic bacteria [19,28].…”

Section: Introductionmentioning

confidence: 99%

Serotonin Exposure Improves Stress Resistance, Aggregation, and Biofilm Formation in the Probiotic Enterococcus faecium NCIMB10415

Scardaci

Manfredi

Barberis

et al. 2021

Microbiology Research

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The role of the microbiota–gut–brain axis in maintaining a healthy status is well recognized. In this bidirectional flux, the influence of host hormones on gut bacteria is crucial. However, data on commensal/probiotics are scarce since most reports analyzed the effects of human bioactive compounds on opportunistic strains, highlighting the risk of increased pathogenicity under stimulation. The present investigation examined the modifications induced by 5HT, a tryptophan-derived molecule abundant in the intestine, on the probiotic Enterococcus faecium NCIMB10415. Specific phenotypic modifications concerning the probiotic potential and possible effects of treated bacteria on dendritic cells were explored together with the comparative soluble proteome evaluation. Increased resistance to bile salts and ampicillin in 5HT-stimulated conditions relate with overexpression of specific proteins (among which Zn-beta-lactamases, a Zn-transport protein and a protein involved in fatty acid incorporation into the membrane). Better auto-aggregating properties and biofilm-forming aptitude are consistent with enhanced QS peptide transport. Concerning interaction with the host, E. faecium NCIMB10415 enhanced dendritic cell maturation, but no significant differences were observed between 5HT-treated and untreated bacteria; meanwhile, after 5HT exposure, some moonlight proteins possibly involved in tissue adhesion were found in higher abundance. Finally, the finding in stimulated conditions of a higher abundance of VicR, a protein involved in two-component signal transduction system (VicK/R), suggests the existence of a possible surface receptor (VicK) for 5HT sensing in the strain studied. These overall data indicate that E. faecium NCIMB10415 modifies its physiology in response to 5HT by improving bacterial interactions and resistance to stressors.

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The Serotonin Neurotransmitter Modulates Virulence of Enteric Pathogens

Cited by 81 publications

References 67 publications

Sexual Dimorphism of the Neuroimmunoendocrine Response in the Spleen During a Helminth Infection: A New Role for an Old Player?

Sexual Dimorphism of the Neuroimmunoendocrine Response in the Spleen During a Helminth Infection: A New Role for an Old Player?

A Novel Small RNA Promotes Motility and Virulence of Enterohemorrhagic Escherichia coli O157:H7 in Response to Ammonium

Serotonin Exposure Improves Stress Resistance, Aggregation, and Biofilm Formation in the Probiotic Enterococcus faecium NCIMB10415

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