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Title:Sweet relief: regulating the response to glucose phosphate stress by the small RNA SgrS & Co.
Author(s):Sun, Yan
Director of Research:Vanderpool, Carin K.
Doctoral Committee Chair(s):Vanderpool, Carin K.
Doctoral Committee Member(s):Imlay, James A.; Cronan, John E.; Gardner, Jeffrey F.
Department / Program:Microbiology
Degree Granting Institution:University of Illinois at Urbana-Champaign
Subject(s):Glucose phosphate stress
alpha-methyl glucoside
Small regulatory RNA
Sugar efflux transporter
Abstract:Cells use complex mechanisms to regulate glucose transport and metabolism to achieve optimal energy and biomass production while avoiding accumulation of toxic metabolites. Glucose transport and glycolytic metabolism carries the risk of the buildup of phosphosugars, which can inhibit growth at high concentrations. Many enteric bacteria cope with phosphosugar accumulation and associated stress (i.e., phosphosugar stress) by producing a small RNA (sRNA) regulator, SgrS, which represses translation of sugar transporter mRNAs (ptsG and manXYZ) and enhances translation of a sugar phosphatase mRNA (yigL). Despite a molecular understanding of individual target regulation by SgrS, previously little was known about how coordinated regulation of these targets contributes to the rescue of cell growth during phosphosugar stress. The first part of my graduate study examines how SgrS regulation of different targets impacts growth under different nutritional conditions upon phosphosugar stress. The severity of stress-associated growth inhibition depended on nutrient availability. Cells that were stressed during growth in rich media required SgrS regulation of sugar transporter mRNAs (ptsG or manXYZ). However, repression of transporter mRNAs was insufficient for growth rescue during stress in nutrient-poor minimal media; here SgrS regulation of the phosphatase (yigL) and as-yet-undefined targets also contributed to growth rescue. These results suggest that SgrS and perhaps other sRNAs are flexible regulators that modulate expression of multi-gene regulons in order to allow cells to adapt to an array of stress conditions. Moreover, regulation of only a subset of an sRNAs targets may be important in a given environment. The gene located directly downstream of sgrS is setA, and the gene organization of sgrR, sgrS and setA is conserved in numerous enteric species, prompting the hypothesis that SetA contributes to the glucose-phosphate stress response. SetA is a proton motive force-driven efflux pump capable of transporting various sugars and sugar analogs in vitro. The second part of my graduate study shows that setA expression is induced in response to glucose-phosphate stress, and this requires SgrR. Under stress conditions, setA is cotranscribed with sgrS from the sgrS promoter. A setA mutant exhibits a growth defect under stress conditions that can be complemented by setA in trans, suggesting that SetA contributes to the optimal cellular recovery from stress. Despite previous in vitro evidence that SetA can promote efflux of the stress-causing glucose analog α-methyl glucoside, in vivo data in this study indicate that SetA is not the major efflux pump responsible for removal of α-methyl glucoside under stress conditions.
Issue Date:2013-02-03
Rights Information:Copyright 2012 Yan Sun
Date Available in IDEALS:2013-02-03
Date Deposited:2012-12

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