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.
Enterohemorrhagic (EHEC) is a commonly occurring foodborne pathogen responsible for numerous multistate outbreaks in the United States. It is known to infect the host gastrointestinal tract, specifically, in locations associated with lymphoid tissue. These niches serve as sources of enteric neurotransmitters, such as epinephrine and norepinephrine, that are known to increase virulence in several pathogens, including enterohemorrhagic The mechanisms that allow pathogens to target these niches are poorly understood. We previously reported that 3,4-dihydroxymandelic acid (DHMA), a metabolite of norepinephrine produced by , is a chemoattractant for the nonpathogenic RP437 strain. Here we report that DHMA is also a chemoattractant for EHEC. In addition, DHMA induces the expression of EHEC virulence genes and increases attachment to intestinal epithelial cells in a QseC-dependent manner. We also show that DHMA is present in murine gut fecal contents and that its production requires the presence of the commensal microbiota. On the basis of its ability to both attract and induce virulence gene expression in EHEC, we propose that DHMA acts as a molecular beacon to target pathogens to their preferred sites of infection.
Healthcare-associated infections (HAIs) caused by pathogenic bacteria are a worldwide problem and responsible for numerous cases of morbidity and mortality. Exogenous cross-contamination is one of the main mechanisms contributing to such infections. This work investigates the potential of hydrophobically modified nanoporous silica aerogel as an antiadhesive hygienic material that can inhibit exogenous bacterial contamination. Nanoporous silica aerogels were synthesized via sol-gel polymerization of tetraethyl orthosilicate and hydrophobized using trimethylsilyl chloride. Bacterial adhesion characteristics were evaluated via dip-inoculation in suspensions of Gram-negative Escherichia coli O157:H7 and Gram-positive Staphylococcus aureus. The attachment of E. coli O157:H7 and S. aureus to hydrophobic nanoporous silica aerogel (HNSA) was found to be significantly lower than that to hydrophilic and hydrophobic nonporous silica materials: 99.91% (E. coli O157:H7) and 99.93% (S. aureus) reduction in comparison to hydrophilic nonporous silica, and 82.95% (E. coli O157:H7) and 84.90% (S. aureus) reduction in comparison to hydrophobic nonporous silica. These results suggest that the use of HNSA as surfaces that come into contact with bacterial pathogens in the healthcare environment can improve bacterial hygiene, and therefore may reduce the rate of HAIs.
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