Indole Acts as an Extracellular Cue Regulating Gene Expression inVibrio cholerae

Abstract

Indole has been proposed to act as an extracellular signal molecule influencing biofilm formation in a range of bacteria. For this study, the role of indole in Vibrio cholerae biofilm formation was examined. It was shown that indole activates genes involved in vibrio polysaccharide (VPS) production, which is essential for V. cholerae biofilm formation. In addition to activating these genes, it was determined using microarrays that indole influences the expression of many other genes, including those involved in motility, protozoan grazing resistance, iron utilization, and ion transport. A transposon mutagenesis screen revealed additional components of the indole-VPS regulatory circuitry. The indole signaling cascade includes the DksA protein along with known regulators of VPS production, VpsR and CdgA. A working model is presented in which global control of gene expression by indole is coordinated through 54 and associated transcriptional regulators.Bacterial cells synthesize myriad small organic molecules to signal and adapt to environmental, physiological, and population structure changes. These molecules include extracellular signals such as acyl homoserine lactones, butyrolactones, quinolones, a furanosyl borate diester, oligopeptides, 3-hydroxypalmitic acid methyl ester, and a hydroxyketone and intracellular signals including cyclic nucleotides and ppGpp (25; reviewed in reference 11). The phenotypic response to signaling compounds often involves traits that are beneficial under adverse conditions, such as biofilm formation, virulence, motility, bioluminescence, sporulation, competence, modification of carbon and energy utilization, and macromolecule biosynthesis.Indole is a relatively recent addition to the list of signaling molecules used by bacteria and is produced as a by-product of the breakdown of tryptophan by the enzyme tryptophanase (TnaA) (18). Since the expression of the tnaA gene is controlled by catabolite repression, it is transcribed only during carbon limitation (57). As a result of this regulation, large quantities of indole are produced during the stationary phase of growth. Indole has long been known to act as a chemorepellent of Escherichia coli (52), but only more recently has indole also been shown to control the expression of a wide assortment of genes and phenotypes unrelated to chemotaxis in many different bacteria. For example, in E. coli indole controls the expression of genes involved in amino acid metabolism (54), plasmid maintenance (13), and quorum sensing (32), among other functions (14). Additionally, indole may function as an interspecies signal contributing to biofilm formation in an assortment of different bacteria known to carry a copy of the tryptophanase gene (36). In E. coli specifically, the indoledriven transcriptional response, which controls subsequent biofilm formation, is known to be controlled by the quorumsensing transcriptional regulator SdiA (32).It was previously shown that control of biofilm formation by indole also extends to the etiological agent of the ...

Efficacy of 7‐benzyloxyindole and other halogenated indoles to inhibit Candida albicans biofilm and hyphal formation

“…In Pseudomonas putida , signalling molecules such as indole enhances TtgGHI efflux pump that are relevant for antibiotic resistance (Molina‐Santiago et al ., 2014). The previous studies have reported that indole inhibits biofilm formation and suppresses the virulence of bacterial strains such as Staphylococcus aureus , Agrobacterium tumefaciens (Lee and Lee, 2010; Lee et al ., 2013, 2015a,b; Lee et al ., 2016) and Vibrio cholera (Mueller et al ., 2009). Likewise, indole derivatives such as 7‐fluoroindole, 7‐hydroxyindole, 3‐indolyl acetonitrile and 2‐aminobenzimidazoles have been reported to exhibit antimicrobial activities against pathogenic bacteria (Lee et al ., 2009, 2011, 2012, 2015a,b; Frei et al ., 2012).…”

Sticky Situations: Key Components That Control Bacterial Surface Attachment

“…For instance, indole, which is prevalent in the gastrointestinal tract, has been proposed to act as an extracellular signal molecule influencing biofilm formation in a range of bacteria. In V. cholerae, indole has been shown to activate genes involved in VPS production that are essential for vps-dependent biofilm development (114). In E. coli O157:H7, indole has the opposite effect of reducing attachment to both abiotic surfaces and epithelial cells (8).…”

Mini-review: Inhibition of biofouling by marine microorganisms

“…Recently, indole has been identified as a signal molecule involved in the formation of biofilm by V. cholerae (Mueller et al 2009), controlling the vps genes which regulate the production of Vibrio polysaccharides that make up the bulk of a biofilm matrix. Several natural products (containing indole moieties) extracted from a Mediterranean gorgonian coral were shown to be effective at inhibiting the formation of biofilms by 3 marine bacteria (Penez et al 2011).…”

“…Indole-producing bacteria also can inhibit the growth of pathogens (see antibacterial activity). As the genes controlled by indole are now characterised in V. cholerae (Mueller et al 2009), it will be of interest to test whether the alkaloids produced by marine organisms are capable of interfering with bacterial indole-mediated signalling.…”