Effects of indole on drug resistance and virulence of Salmonella enterica serovar Typhimurium revealed by genome-wide analyses

Abstract

BackgroundMany Gram-positive and Gram-negative bacteria produce large quantities of indole as an intercellular signal in microbial communities. Indole demonstrated to affect gene expression in Escherichia coli as an intra-species signaling molecule. In contrast to E. coli, Salmonella does not produce indole because it does not harbor tnaA, which encodes the enzyme responsible for tryptophan metabolism. Our previous study demonstrated that E. coli-conditioned medium and indole induce expression of the AcrAB multidrug efflux pump in Salmonella enterica serovar Typhimurium for inter-species communication; however, the global effect of indole on genes in Salmonella remains unknown.ResultsTo understand the complete picture of genes regulated by indole, we performed DNA microarray analysis of genes in the S. enterica serovar Typhimurium strain ATCC 14028s affected by indole. Predicted Salmonella phenotypes affected by indole based on the microarray data were also examined in this study. Indole induced expression of genes related to efflux-mediated multidrug resistance, including ramA and acrAB, and repressed those related to host cell invasion encoded in the Salmonella pathogenicity island 1, and flagella production. Reduction of invasive activity and motility of Salmonella by indole was also observed phenotypically.ConclusionOur results suggest that indole is an important signaling molecule for inter-species communication to control drug resistance and virulence of S. enterica.

Role of Indole Production on Virulence of Vibrio cholerae Using Galleria mellonella Larvae Model

“…The protective role of indole towards various stresses has been described in several microorganisms possibly through inducing efflux system or biofilm formation [31][32][33]. High level of extracellular indole was detected in E. coli in the stress condition of antibiotics treatment and supplementation or increase production of indole enhanced cell survival [10,13,14].…”

Indole production by the tryptophanase TnaA in Escherichia coli is determined by the amount of exogenous tryptophan

“…Indeed, indole produced from just a few cells can protect a large population of E. coli against several antibiotics . Indole-regulated behaviours also extend to inter-species communication by affecting efflux-mediated multidrug resistance, flagella synthesis, virulence factor expression and host cell invasion by indole-non-producers like Salmonella enterica, Pseudomonas aeruginosa and even the yeast Candida albicans (Lee et al, 2009;Nikaido et al, 2011Nikaido et al, , 2012Oh et al, 2012;Raut et al, 2012). Finally, indole and other tryptophan-derived metabolites balance inflammation in the mammalian intestinal tract (Bansal et al, 2010;Keszthelyi et al, 2012;Nicholson et al, 2012) and strengthen the barrier function of epithelial tight junctions (Bansal et al, 2010;Keszthelyi et al, 2012;Nicholson et al, 2012).…”

Indole inhibits bacterial quorum sensing signal transmission by interfering with quorum sensing regulator folding

“…Escherichia coli can excrete considerable amounts of indole and acetate in the stationary phase (Helling et al, 2002;Kobayashi et al, 2006). Indole has received great attention because of its extensive effects on various biological functions in the bacterial population, such as biofilm formation, antibiotic resistance and virulence (Lee et al, 2007(Lee et al, , 2009Chu et al, 2012;Nikaido et al, 2012;Vega et al, 2012). Indole has been known to be exported by the AcrEF-TolC pump (Kawamura-Sato et al, 1999), although others have reported that indole freely diffuses across membranes and AcrEF was not required for indole export (Piñero-Fernandez et al, 2011).…”