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

Eiji Nikaido123, Etienne Giraud45, Sylvie Baucheron45, Suguru Yamasaki123, Agnès Wiedemann45, Kousuke Okamoto3, Tatsuya Takagi3, Akihito Yamaguchi23, Axel Cloeckaert45* and Kunihiko Nishino1*

Author Affiliations

1 Laboratory of Microbiology and Infectious Diseases, Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka, 567-00447, Japan

2 Department of Cell Membrane Biology, Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka, Japan

3 Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Osaka, Japan

4 INRA, UMR1282 Infectiologie et Santé Publique, F-37380, Nouzilly, France

5 Université François Rabelais de Tours, UMR1282 Infectiologie et Santé Publique, F-37000, Tours, France

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Gut Pathogens 2012, 4:5  doi:10.1186/1757-4749-4-5

Published: 25 May 2012



Many 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.


To 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.


Our results suggest that indole is an important signaling molecule for inter-species communication to control drug resistance and virulence of S. enterica.

AcrAB; Indole; RamA; Salmonella; SPI-1