Thus, the indoleinduced drug tolerance seen by Vega et al. could result from induction on the multidrug resistance (MDR) AcrABTolC efflux technique, major to increased tolerance to these two drugs. This hypothesis is noted by the authors but dismissed immediately after their RTPCR experiments showed that expression of your ramA gene was reduced in the presence of indole. We’re perplexed by this observation since it conflicts with all prior research like measurements working with gene reporter constructs, RTPCR, microarray, and Western blotting (two), which reveal that ramA/RamA is induced by indole in a lot of different Salmonella strains which includes strain LT2 made use of by Vega et al. in their experiments. Moreover, the authors used these RTPCR data as proof that efflux is not involved in the phenotype. We think that this is a mistaken assumption for two causes. First, efflux was not measured. That is surprising mainly because efflux of ciprofloxacin as well as other compounds may be measured quickly applying among many published approaches to quantify accumulation or efflux of fluorescent substrates (3, 4). Second, regulation of MDR efflux pumps in Gramnegative bacteria is complicated and multifactorial. For example, other transcription components, such as MarA, SoxS, and Rob, also can regulate expression of MDR efflux pumps, and indole induces expression of soxS in E. coli (five). 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 Ailments, Institute of Scientific and Industrial Research, Osaka University, Osaka 5670047, Japan1 Vega NM, Allison KR, Samuels AN, Klempner MS, Collins JJ (2013) Salmonella typhimurium intercepts Escherichia coli signaling to enhance antibiotic tolerance. Proc Natl Acad Sci USA 110(35): 144204425. 2 Nikaido E, et al. (2012) Effects of indole on drug resistance and virulence of Salmonella enterica serovar Typhimurium revealed by genomewide analyses. Gut Pathog four(1):5. three Webber M, Coldham N (2010) Measuring the activity of active efflux in Gramnegative bacteria. Antibiotic Resistance Protocols, Approaches in Molecular Biology, eds Gillespie SH, McHugh TD (Humana Press), Vol 642, pp 17380. four Bohnert JA, Schuster S, SzymaniakVits M, Kern WV (2011) Determination of realtime efflux phenotypes in Escherichia coli AcrB binding pocket phenylalanine mutants working with a 1,2dinaphthylamine efflux assay.Buy74663-77-7 PLoS One particular six(6):e21196.1889290-53-2 Formula five Lee J, Jayaraman A, Wood TK (2007) Indole is definitely an interspecies biofilm signal mediated by SdiA.PMID:33587679 BMC Microbiol 7:42.Antimicrobials Study Group, Institute of Microbiology and infection, School of Immunity and Infection, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UnitedAuthor contributions: J.M.A.B., A.C., K.N., and L.J.V.P. wrote the paper. The authors declare no conflict of interest.To whom correspondence ought to be addressed. E-mail: l.j.v. [email protected]/cgi/doi/10.1073/pnas.PNAS | November 26, 2013 | vol. 110 | no. 48 | ELETTER
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