The microbiota metabolite indole inhibits Salmonella virulence: Involvement of the PhoPQ two-component system

Autor: Michael Li, Zeni Crisp, Arul Jayaraman, Rebekah Riordan, Nandita Kohli, Robert C. Alaniz
Jazyk: angličtina
Rok vydání: 2018
Předmět:
0301 basic medicine
Bacterial Diseases
Salmonella typhimurium
Salmonella
Indoles
Salmonellosis
lcsh:Medicine
Gene Expression
medicine.disease_cause
Pathology and Laboratory Medicine
Epithelium
White Blood Cells
Mice
Heterocyclic Compounds
Animal Cells
Medicine and Health Sciences
lcsh:Science
Pathogen
Multidisciplinary
Virulence
Effector
Organic Compounds
Microbiota
Genomics
Bacterial Pathogens
Chemistry
Infectious Diseases
Medical Microbiology
Physical Sciences
Pathogens
Cellular Types
Anatomy
Research Article
Pathogen Motility
Virulence Factors
Immune Cells
030106 microbiology
Immunology
Colonisation resistance
Microbial Genomics
Biology
Microbiology
Cell Line
03 medical and health sciences
Enterobacteriaceae
Bacterial Proteins
medicine
Genetics
Animals
Humans
Microbial Pathogens
Indole test
Blood Cells
Bacteria
Macrophages
lcsh:R
Organic Chemistry
Biofilm
Tryptophan
Chemical Compounds
Organisms
Biology and Life Sciences
Epithelial Cells
Cell Biology
Gene Expression Regulation
Bacterial
030104 developmental biology
Biological Tissue
lcsh:Q
Microbiome
HeLa Cells
Zdroj: PLoS ONE
PLoS ONE, Vol 13, Iss 1, p e0190613 (2018)
ISSN: 1932-6203
Popis: The microbial community present in the gastrointestinal tract is an important component of the host defense against pathogen infections. We previously demonstrated that indole, a microbial metabolite of tryptophan, reduces enterohemorrhagic Escherichia coli O157:H7 attachment to intestinal epithelial cells and biofilm formation, suggesting that indole may be an effector/attenuator of colonization for a number of enteric pathogens. Here, we report that indole attenuates Salmonella Typhimurium (Salmonella) virulence and invasion as well as increases resistance to colonization in host cells. Indole-exposed Salmonella colonized mice less effectively compared to solvent-treated controls, as evident by competitive index values less than 1 in multiple organs. Indole-exposed Salmonella demonstrated 160-fold less invasion of HeLa epithelial cells and 2-fold less invasion of J774A.1 macrophages compared to solvent-treated controls. However, indole did not affect Salmonella intracellular survival in J774A.1 macrophages suggesting that indole primarily affects Salmonella invasion. The decrease in invasion was corroborated by a decrease in expression of multiple Salmonella Pathogenicity Island-1 (SPI-1) genes. We also identified that the effect of indole was mediated by both PhoPQ-dependent and independent mechanisms. Indole also synergistically enhanced the inhibitory effect of a short chain fatty acid cocktail on SPI-1 gene expression. Lastly, indole-treated HeLa cells were 70% more resistant to Salmonella invasion suggesting that indole also increases resistance of epithelial cells to colonization. Our results demonstrate that indole is an important microbiota metabolite that has direct anti-infective effects on Salmonella and host cells, revealing novel mechanisms of pathogen colonization resistance.
Databáze: OpenAIRE
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