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Cited by 132Bacterial biofilms and quorum sensingEscherichia coli research studiesMolecular Communication and Nanonetworks

Serotonin Activates Bacterial Quorum Sensing and Enhances the Virulence of Pseudomonas aeruginosa in the Host

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Knecht, Leslie D., O'Connor, Gregory, Mittal, Rahul, Liu, Xue Z., Daftarian, Pirouz, Deo, Sapna K., Daunert, Sylvia·2016·EBioMedicine
DOI 10.1016/j.ebiom.2016.05.037PMC PMC4972532
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Abstract

Bacteria in humans play an important role in health and disease. Considerable emphasis has been placed in understanding the role of bacteria in host-microbiome interkingdom communication. Here we show that serotonin, responsible for mood in the brain and motility in the gut, can also act as a bacterial signaling molecule for pathogenic bacteria. Specifically, we found that serotonin acts as an interkingdom signaling molecule via quorum sensing and that it stimulates the production of bacterial virulence factors and increases biofilm formation in vitro and in vivo in a novel mouse infection model. This discovery points out at roles of serotonin both in bacteria and humans, and at phenotypic implications not only manifested in mood behavior but also in infection processes in the host. Thus, regulating serotonin concentrations in the gut may provide with paradigm shifting therapeutic approaches.

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  • 5-HT modulates bacterial motility and induces expression of virulence genes in bacteria via a quorum-sensing mechanism.

    “As a neuroendocrine signal of host-microbe crosstalk, 5-HT has been shown to modulate bacterial motility and induce the expression of virulence genes in bacteria via a quorum-sensing mechanism (Biaggini et al., 2015;Knecht et al., 2016).”

    From The Microbiota-Gut-Brain Axis (2019) · cites this paper as Knecht et al., 2016

    The Results sections report that serotonin activates the las quorum-sensing pathway and increases production of virulence factors in P. aeruginosa. But the paper reports no increase in swarming motility after serotonin was added; it also measures virulence-factor production rather than directly demonstrating increased virulence-gene expression. (LLM, conf=0.89)

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  1. Beatson S.A. Whitchurch C.B. Sargent J.L. Levesque R.C. Mattick J.S. Differential regulation of twitching motility and elastase production by Vfr in Pseudomonas aeruginosa J. Bacteriol. 184 2002 3605 3613 12057955 PMC135129
  2. Berger M. Gray J.A. Roth B.L. The expanded biology of serotonin Annu. Rev. Med. 60 2009 355 366 19630576 PMC5864293
  3. Bravo J.A. Forsythe P. Chew M.V. Escaravage E. Savignac H.M. Dinan T.G. Bienenstock J. Cryan J.F. Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve Proc. Natl. Acad. Sci. U. S. A. 108 2011 16050 16055 21876150 PMC3179073
  4. Clarke M.B. Hughes D.T. Zhu C. Boedeker E.C. Sperandio V. The QseC sensor kinase: a bacterial adrenergic receptor PNAS 103 2006 10420 10425 16803956 PMC1482837
  5. Clarke G. Stilling R.M. Kennedy P.J. Stanton C. Cryan J.F. Dinan T.G. Minireview: gut microbiota: the neglected endocrine organ Mol. Endocrinol. 28 2014 1221 1238 24892638 PMC5414803
  6. Cryan J.F. Dinan T.G. Mind-altering microorganisms: the impact of the gut microbiota on brain and behaviour Nat. Rev. Neurosci. 13 2012 701 712 22968153
  7. Davies D.G. Parsek M.R. Pearson J.P. Iglewski B.H. Costerton J.W. Greenberg E.P. The involvement of cell-to-cell signals in the development of a bacterial biofilm Science 280 1998 295 298 9535661
  8. De Kievit T.R. Gillis R. Marx S. Brown C. Iglewski B.H. Quorum-sensing genes in Pseudomonas aeruginosa biofilms: their role and expression patterns Appl. Environ. Microbiol. 67 2001 1865 1873 11282644 PMC92808
  9. Desbonnet L. Garrett L. Clarke G. Kiely B. Cryan J.F. Dinan T.G. Effects of the probiotic Bifidobacterium infantis in the maternal separation model of depression Neuroscience 170 2010 1179 1188 20696216
  10. Erspamer V. Occurence of Indolealkylamines in Nature: Springer-Verlag) 1966
  11. Hsiao E.Y. Mcbride S.W. Hsien S. Sharon G. Hyde E.R. Mccue T. Codelli J.A. Chow J. Reisman S.E. Petrosino J.F. Patterson P.H. Mazmanian S.K. Microbiota modulate behavioral and physiological abnormalities associated with neurodevelopmental disorders Cell 155 2013 1451 1463 24315484 PMC3897394
  12. Knights D. Lassen K.G. Xavier R.J. Advances in inflammatory bowel disease pathogenesis: linking host genetics and the microbiome Gut 62 2013 1505 1510 24037875 PMC3822528
  13. Kumari A. Pasini P. Deo S.K. Flomenhoft D. Shashidhar H. Daunert S. Biosensing systems for the detection of bacterial quorum signaling molecules Anal. Chem. 78 2006 7603 7609 17105149
  14. Lee Y.K. Mazmanian S.K. Has the microbiota played a critical role in the evolution of the adaptive immune system? Science 330 2010 1768 1773 21205662 PMC3159383
  15. Lyte M. Microbial endocrinology in the microbiome-gut-brain axis: how bacterial production and utilization of neurochemicals influence behavior PLoS Pathog. 9 2013 e1003726 PMC3828163 24244158
  16. Marcobal A. Kashyap P.C. Nelson T.A. Aronov P.A. Donia M.S. Spormann A. Fischbach M.A. Sonnenburg J.L. A metabolomic view of how the human gut microbiota impacts the host metabolome using humanized and gnotobiotic mice ISME J 7 2013 1933 1943 23739052 PMC3965317
  17. Mittal R. Wang Y. Hunter C.J. Gonzalez-Gomez I. Prasadarao N.V. Brain damage in newborn rat model of meningitis by Enterobacter sakazakii: a role for outer membrane protein A Lab. Investig. 89 2009 263 277 19139724 PMC3256236
  18. Miwa J. Echizen H. Matsueda K. Umeda N. Patients with constipation-predominant irritable bowel syndrome (IBS) may have elevated serotonin concentrations in colonic mucosa as compared with diarrhea-predominant patients and subjects with normal bowel habits Digestion 63 2001 188 194 11351146
  19. Odobasic D. Kitching A.R. Semple T.J. Holdsworth S.R. Endogenous myeloperoxidase promotes neutrophil-mediated renal injury, but attenuates T cell immunity inducing crescentic glomerulonephritis J. Am. Soc. Nephrol. 18 2007 760 770 17267745
  20. Oleskin A.V. Kirovskaia T.A. Botvinko I.V. Lysak L.V. Effect of serotonin (5-hydroxytryptamine) on the growth and differentiation of microorganisms Mikrobiologiia 67 1998 305 312 9702725
  21. O'mahony S.M. Clarke G. Borre Y.E. Dinan T.G. Cryan J.F. Serotonin, tryptophan metabolism and the brain-gut-microbiome axis Behav. Brain Res. 277 2015 32 48 25078296
  22. Pearson J.P. Pesci E.C. Iglewski B.H. Roles of Pseudomonas aeruginosa las and rhl quorum-sensing systems in control of elastase and rhamnolipid biosynthesis genes J. Bacteriol. 179 1997 5756 5767 9294432 PMC179464
  23. Smith K.M. Bu Y. Suga H. Induction and inhibition of Pseudomonas aeruginosa quorum sensing by synthetic autoinducer analogs Chem. Biol. 10 2003 81 89 12573701
  24. Tillisch K. Labus J. Kilpatrick L. Jiang Z. Stains J. Ebrat B. Guyonnet D. Legrain-Raspaud S. Trotin B. Naliboff B. Mayer E.A. Consumption of fermented milk product with probiotic modulates brain activity Gastroenterology 144 2013 1394 1401 (1401 e1-4) 23474283 PMC3839572
  25. Valiente E. Lee C. Hor L. Fouz B. Amaro C. Role of the metalloprotease Vvp and the virulence plasmid pR99 of Vibrio vulnificus serovar E in surface colonization and fish virulence Environ. Microbiol. 10 2007 328 338 18028416
  26. Waters C.M. Lu W. Rabinowitz J.D. Bassler B.L. Quorum sensing controls biofilm formation in Vibrio cholerae through modulation of cyclic di-GMP levels and repression of vpsT J. Bacteriol. 190 2008 2527 2536 18223081 PMC2293178
  27. Yano J.M. Yu K. Donaldson G.P. Shastri G.G. Ann P. Ma L. Nagler C.R. Ismagilov R.F. Mazmanian S.K. Hsiao E.Y. Indigenous bacteria from the gut microbiota regulate host serotonin biosynthesis Cell 161 2015 264 276 25860609 PMC4393509
  28. Zhang J. Wu X.Y. Yu F.S. Inflammatory responses of corneal epithelial cells to Pseudomonas aeruginosa infection Curr. Eye Res. 30 2005 527 534 16020286 PMC2666384

Cited by

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Authors
Knecht, L. D., O'Connor, G., Mittal, R., Liu, X. Z., Daftarian, P., Deo, S. K., & Daunert, S.
Affiliations
University of Miami (US)
Corresponding author
Daunert, Sylvia
ORCID
Venue
EBioMedicine
Publisher
Elsevier BV
Published
2016-07
Volume
9
Pages
161-169
ISSN
2352-3964 (ISSN-L)
DOI
10.1016/j.ebiom.2016.05.037
PMC
PMC4972532
OpenAlex
W2408617109
Cited by
132
References
3
Citations by year
2026: 8 · 2025: 17 · 2024: 14 · 2023: 11 · 2022: 18 · 2021: 23 · 2020: 19 · 2019: 11 · 2018: 4 · 2017: 4 · 2016: 3
FWCI
3.81
Type
journal article
Language
en
Update notices
erratum (2017-09-01)
Open access
Licence
Locations
  • EBioMedicine (publishedVersion, cc-by-nc-nd)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Science Foundation (ECC-08017788, CHE-1506740)
  • Department of Defense Peer Reviewed Medical Research Program (PRMRP) Discover Award (W1XWH-13-1-0343)
  • National Institutes of Health (R01GM047915, R01DC005575, R01DC012546, R01DC012115)
  • National Science Foundation Integrative Graduate Education Research Traineeship (DGE-0653710)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bacterial biofilms and quorum sensing
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
  • Physical Sciences › Engineering › Biomedical Engineering › Molecular Communication and Nanonetworks
Keywords
serotonin, Pseudomonas aeruginosa, bacterial quorum sensing, interkingdom signaling, bacterial virulence factors, biofilm formation, mouse infection model, gut microbiota, bacterial virulence regulation
MeSH terms
Animals, Bacterial Proteins, Catalase, Female, Injections, Intraperitoneal, Intestinal Mucosa, Intestines, Malondialdehyde, Mice, Inbred C57BL, Microscopy, Electron, Scanning, Peroxidase, Peptide Hydrolases, Phenotype, Pregnancy, Pseudomonas aeruginosa, Serotonin, Virulence, Cytokines, Mice, Quorum Sensing

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