Indole and 7-hydroxyindole diminish Pseudomonas aeruginosa virulence.
Bottom Line: Corroborating these microarray results, indole and 7HI decreased production of pyocyanin, rhamnolipid, PQS and pyoverdine and enhanced antibiotic resistance.In addition, indole affected the utilization of carbon, nitrogen and phosphorus, and 7HI abolished swarming motility.Hence, indole-related compounds have potential as a novel antivirulence approach for the recalcitrant pathogen P. aeruginosa.
Affiliation: Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX 77843-3122, USA.Show MeSH
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Mentions: Quorum sensing is related to virulence as has been shown by whole‐transcriptome studies of P. aeruginosa with 3O‐C12‐HSL and C4‐HSL (Schuster et al., 2003; Wagner et al., 2003) and PQS (Bredenbruch et al., 2006). Here, the addition of indole and 7HI resulted in an opposite pattern of gene expression of the mexGHI‐opmD multidrug efflux genes and many virulence genes compared with gene expression with the two exogenous AHLs. For example, the addition of the AHLs consistently induced the mexGHI‐opmD genes, genes involved in phenazine synthesis and PQS synthesis, and the flp–tad–rcp gene cluster (Schuster et al., 2003; Wagner et al., 2003), while indole and 7HI repressed these genes (Table 1). Similarly, the addition of PQS most significantly induced virulence genes involved in pyochelin synthesis (pch operon) (Bredenbruch et al., 2006) whereas indole repressed the pch operon. Genes involved in small molecule transport (PA2328, PA2329, PA2330 and PA2331) were also induced by AHLs (Schuster et al., 2003), while indole repressed them. Furthermore, the addition of pyocyanin, a physiological terminal signal molecule for the upregulation of QS‐controlled genes (Dietrich et al., 2006), induced mexGHI‐opmD and a possible regulator/putative monooxygenase for pyocyanin synthesis, PA2274 (Dietrich et al., 2006), while indole and 7HI repressed PA2274 (Table 1). In addition to the whole‐transcriptome data, our virulence factor assays (Fig. 1) clearly show that indole and 7HI inhibit QS‐controlled virulence factors. Taken together, indole and 7HI decrease the production of antimicrobial compounds and virulence factors in P. aeruginosa. A conceptual model of the interaction of indole and 7HI on cellular phenotypes of P. aeruginosa is shown in Fig. 5.
Affiliation: Artie McFerrin Department of Chemical Engineering, Texas A&M University, College Station, TX 77843-3122, USA.