Bistability in myo -Inositol Utilization by Salmonella enterica Serovar Typhimurium

Autor: Carsten Kröger, Joachim Ellwart, Thilo M. Fuchs, Shabarinath Srikumar
Rok vydání: 2011
Předmět:
Zdroj: Journal of Bacteriology. 193:1427-1435
ISSN: 1098-5530
0021-9193
Popis: Phenotypic variation is widespread among prokaryotes, and its underlying molecular mechanisms include genetic changes such as genomic inversion and strand-slippage mechanisms, epigenetic variations depending on DNA methylation, and feedback-based multistability characterized by at least two distinct phenotypes within an isogenic population (36). Per definition, bistability must arise stochastically at the cellular level (9). A common regulatory arrangement exhibiting bistability includes a positive-feedback loop with a cooperative response to an activator (10). This was first described for lactose utilization by Escherichia coli in which a population is split into cells highly or not at all expressing the lac operon (11, 28). Further prominent examples are the bistable switch between lysogeny and lysis of bacteriophage λ depending on the fragile balance between the regulators Cro and CI (4), and the Bacillus subtilis K-status (competence) system in which 10 to 20% of the cells in stationary phase highly express genes permitting transformation competence (24, 35). The survival of Staphylococcus aureus against antibiotic treatment requires that some cells called persisters enter a condition of reduced growth (5), and population heterogeneity is also observed during B. subtilis sporulation (13). Very recently, it was demonstrated that biofilm formation by Salmonella enterica serovar Typhimurium strain 14028 (S. Typhimurium 14028) involves the bistable expression of CsgD, the major biofilm regulator (14). Even more intriguing, when this pathogen infects hosts, a stochastic switch takes place that results in a self-destructive fraction and another that benefits from the dying one (3). myo-Inositol (MI) is a polyol abundant in soil. The iol genes of S. Typhimurium 14028 responsible for utilization of MI as carbon and energy source are located on a 22.6-kb genomic island (GEI4417/4436) that is absent in all but six Salmonella serovars sequenced thus far (21). All genes on this island necessary for MI degradation are induced during growth with this substrate as the sole carbon source. The catabolic pathway requires IolG and IolE converting MI to 3D-trihydroxycyclohexane-1,2-dione, which is further hydrolyzed by IolD. 5-deoxy-glucuronic acid is isomerized by IolB to 2-deoxy-5-keto-d-gluconic acid that is then phosphorylated by the kinase IolC and degraded to dihydroxyacetone phosphate, acetyl coenzyme A, and CO2. In rich medium, the negative regulator IolR represses all but one promoter of the iol divergon, including its own (21). A protein belonging to the major facilitator superfamily, IolT1, has recently been identified as the predominant MI transporter of S. Typhimurium 14028, and IolR was revealed to also inhibit the transcription of iolT1 (22). The ability to degrade MI is known for the Gram-positive species Bacillus subtilis (26, 39, 41), Corynebacterium glutamicum (20), Clostridium perfringens (17), and Lactobacillus casei BL23 (38), as for several Gram-negative species such as Serratia, Klebsiella, and Pseudomonas (6, 12, 23, 30). Although a comparison of the respective gene clusters revealed a high variability of their chromosomal organization, the negative regulation of the iol genes by the IolR repressor is a common feature of all MI divergons investigated thus far. An intermediate of MI degradation, 2-deoxy-5-keto-d-gluconic acid 6-phosphate (DKP), has been shown to antagonize IolR binding, thus inducing the expression of iol genes (40, 42). A remarkable and unique property of S. Typhimurium 14028 is its long lag phase in the presence of MI. We show here for the first time that phenotypic variation is involved in this growth phenomenon and that the deletion of IolR and the addition of bicarbonate induce growth of the pathogen in MI. A model of the molecular mechanism underlying bistability in the presence of MI is proposed.
Databáze: OpenAIRE