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LETTERAlternative explanation for indole-induced antibiotic tolerance in SalmonellaWe had been interested to study the current publication by Vega et al. (1), which suggests that indole is an interspecies signal that causes Salmonella to turn out to be less susceptible to antibiotics because of activation in the oxidative tension response. Even so, we believe that there’s an alternative explanation for their data: the drug tolerance phenotype is resulting from increased production of one or far more multidrug efflux pumps. The drugs tested by Vega et al., ciprofloxacin and carbenicillin, are recognized substrates from the AcrB transporter, and indole has been shown to induce the production of efflux pumps in each Escherichia coli and Salmonella (two). In Salmonella, induction is mediated by increased expression on the transcriptional activator RamA, which regulates expression of acrAB (2). For that reason, the indole-induced drug tolerance seen by Vega et al. could outcome from induction of the multidrug resistance (MDR) AcrAB-TolC efflux system, top to elevated tolerance to these two drugs. This hypothesis is noted by the authors but dismissed soon after their RT-PCR experiments showed that expression from the ramA gene was lowered within the presence of indole. We are perplexed by this observation because it conflicts with all previous research such as measurements making use of gene reporter constructs, RT-PCR, microarray, and Western blotting (two), which reveal that ramA/RamA is induced by indole in a lot of various Salmonella strains like strain LT2 applied by Vega et al.Astemizole in their experiments. Furthermore, the authors applied these RT-PCR data as evidence that efflux just isn’t involved in the phenotype. We think that this can be a mistaken assumption for two reasons. First, efflux was not measured. This really is surprising for the reason that efflux of ciprofloxacin along with other compounds may be measured simply working with among numerous published procedures to quantify accumulation or efflux of fluorescent substrates (3, four). Second, regulation of MDR efflux pumps in Gram-negative bacteria is complex and multifactorial. As an example, other transcription aspects, like MarA, SoxS, and Rob, may also regulate expression of MDR efflux pumps, and indole induces expression of soxS in E. coli (5). Jessica M. A. Blaira, Axel Cloeckaertb,c, Kunihiko Nishinod, and Laura J. V. Piddocka,aKingdom; bInstitut National de la Recherche Agronomique, UnitMixte de Recherche (UMR)1282 Infectiologie et SantPublique, Nouzilly, France; cUniversitFran is Rabelais de Tours, UMR1282 Infectiologie et SantPublique, Tours, France; and dLaboratory of Microbiology and Infectious Illnesses, Institute of Scientific and Industrial Investigation, Osaka University, Osaka 567-0047, Japan1 Vega NM, Allison KR, Samuels AN, Klempner MS, Collins JJ (2013) Salmonella typhimurium intercepts Escherichia coli signaling to enhance antibiotic tolerance.Gramicidin Proc Natl Acad Sci USA 110(35): 144204425.PMID:24211511 2 Nikaido E, et al. (2012) Effects of indole on drug resistance and virulence of Salmonella enterica serovar Typhimurium revealed by genome-wide analyses. Gut Pathog 4(1):five. 3 Webber M, Coldham N (2010) Measuring the activity of active efflux in Gram-negative bacteria. Antibi.