Abstract
Small noncoding RNAs (sRNAs) with putative regulatory functions in gene expression have been identified in the enteropathogen Salmonella enterica serovar Typhimurium (S. Typhimurium). Two sRNAs are encoded by the genomic island GEI4417/4436 responsible for myo-inositol (MI) degradation, suggesting a role in the regulation of this metabolic pathway. We show that a lack of the sRNA STnc2160, termed RssR, results in a severe growth defect in minimal medium (MM) with MI. In contrast, the second sRNA STnc1740 was induced in the presence of glucose, and its overexpression slightly attenuated growth in the presence of MI. Constitutive expression of RssR led to an increased stability of the reiD mRNA, which encodes an activator of iol genes involved in MI utilization, via interaction with its 5′-UTR. SsrB, a response regulator contributing to the virulence properties of salmonellae, activated rssR transcription by binding the sRNA promoter. In addition, the absence of the RNA chaperone Hfq resulted in strongly decreased levels of RssR, attenuated S. Typhimurium growth with MI, and reduced expression of several iol genes required for MI degradation. Considered together, the extrinsic RssR allows fine regulation of cellular ReiD levels and thus of MI degradation by acting on the reiD mRNA stability.
Highlights
Among them are the two contiguous sRNAs STnc1740 and STnc2160 with a predicted length of 180 and 69 nucleotides, respectively (Fig. 1B)[29,30]. The sequences of both sRNAs are identical in the common laboratory strains LT-2, SL1344, 4/74, and 14028, and are encoded within the genomic island GEI4417/4436 that harbors the genes that are required for MI utilization
STnc2160 is located in the 3′-untranslated region (3′-UTR) of iolB and partially overlaps with the coding region of iolB, whereas STnc1740 lies in the intergenic region between iolB and iolT2 (Fig. 1B)
One class of sRNAs can directly interact with a protein to modify its activity[50,51], whereas the other base-pairs imperfectly in an Hfq-dependent manner with cognate mRNA targets and inhibits initiation by masking the ribosomal binding site followed by mRNA destabilization via RNAse E, or liberate a sequestered RBS, a mechanism termed anti-antisense that results in translational activation[44,52]
Summary
Typhimurium is mainly transmitted by contaminated food, such as egg and its products, poultry, and pork In mice, this pathogen evokes a disseminated infection that serves as a model for human typhoid fever. Typhimurium is challenged by various physical, biochemical, or cellular barriers such as low pH, bile, antimicrobial peptides, colonization resistance or phagocytes[1,2,3] These stress conditions are overcome by specific virulence factors that have been characterized in detail, including those encoded by the Salmonella pathogenicity island 1 (SPI-1) or 2 (SPI-2) that are responsible for epithelial cell invasion, and survival and replication within non-phagocytic host cells or professional phagocytes[4,5,6,7].
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