Repression of Salmonella host cell invasion by aromatic small molecules from the human fecal metabolome

Rafael J.M. Peixoto, Eduardo S. Alves, Melody Wang, Rosana B.R. Ferreira, Alessandra Granato, Jun Han, Hira Gill, Kevan Jacobson, Leandro A. Lobo, Regina M.C.P. Domingues, Christoph H. Borchers, Julian E. Davies, B. Brett Finlay, L. Caetano M. Antunes

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

The human microbiome is a collection of microorganisms that inhabit every surface of the body that is exposed to the environment, generally coexisting peacefully with their host. These microbes have important functions, such as producing vitamins, aiding in maturation of the immune system, and protecting against pathogens. We have previously shown that a small-molecule extract from the human fecal microbiome has a strong repressive effect on Salmonella enterica serovar Typhimurium host cell invasion by modulating the expression of genes involved in this process. Here, we describe the characterization of this biological activity. Using a series of purification methods, we obtained fractions with biological activity and characterized them by mass spectrometry. These experiments revealed an abundance of aromatic compounds in the bioactive fraction. Selected compounds were obtained from commercial sources and tested with respect to their ability to repress the expression of hilA, the gene encoding the master regulator of invasion genes in Salmonella. We found that the aromatic compound 3,4-dimethylbenzoic acid acts as a strong inhibitor of hilA expression and of invasion of cultured host cells by Salmonella. Future studies should reveal the molecular details of this phenomenon, such as the signaling cascades involved in sensing this bioactive molecule.

Original languageEnglish
Article numbere01148-17
JournalApplied and Environmental Microbiology
Volume83
Issue number19
DOIs
Publication statusPublished - 2017
Externally publishedYes

Keywords

  • Aromatic compounds
  • Invasion
  • Salmonella
  • Signaling

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