title: A Novel Small RNA Regulates Tolerance and Virulence in Shigella flexneri by Responding to Acidic Environmental Changes.
abstract: Shigella flexneri is an important cause of bacillary dysentery in developing countries. Small regulatory RNAs (sRNAs) play essential roles in diverse cellular processes. We found a novel sRNA Ssr1 based on RT-PCR, northern blot, and 5'RACE in S. flexneri. Ssr1 responds to acidic environmental changes, as shown by a strong linear correlation between the pH value and Ssr1 expression (R = 0.785, P < 0.05) using the qRT-PCR method. Deletion of Ssr1 results in growth retardation at pH values ranging from 5.0 to 7.0 (P < 0.05), and the survival rate was reduced by 22% in acidic conditions (pH 3.0). Additionally, virulence was significantly increased in an Ssr1 mutant strain, as revealed in a murine lung invasion model and survival model assays. By using the sTarPicker method and proteomic analysis, we considered that DnaK, which is a major factor that confers acidic stress tolerance, may be a direct target of Ssr1. We also found that Ssr1 may enhance virulence by directly targeting OmpA; this leads to altered expression of genes in the type three secretion system (T3SS). This work provides new insight into the mechanism of adaptation to environmental stress and into the pathogenesis of Shigella.
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical SciencesBeijing, China; Center of Computational Biology, Beijing Institute of Basic Medical SciencesBeijing, China.
authors.forename: Ligui
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences Beijing, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences Beijing, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Qi
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences Beijing, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Li
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences Beijing, China.
authors.forename: Leili
authors.initials: L
authors.lastname: Jia
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Xie
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences Beijing, China.
authors.forename: Shaofu
authors.initials: S
authors.lastname: Qiu
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences Beijing, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences Beijing, China.
authors.forename: RongZhang
authors.initials: R
authors.lastname: Hao
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences Beijing, China.
authors.forename: Zhihao
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences Beijing, China.
authors.forename: Xinying
authors.initials: X
authors.lastname: Du
authors.affiliation: Center of Computational Biology, Beijing Institute of Basic Medical Sciences Beijing, China.
authors.forename: Wuju
authors.initials: W
authors.lastname: Li
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences Beijing, China.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Song
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics*; D000818:Animals; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D004405:Dysentery, Bacillary / Q000382:microbiology; D005260:Female; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics*; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008807:Mice, Inbred BALB C; D012329:RNA, Bacterial / Q000235:genetics; D058727:RNA, Small Untranslated / Q000235:genetics*; D012763:Shigella flexneri / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity*; D014158:Transcription, Genetic / Q000235:genetics; D000069296:Type III Secretion Systems / Q000378:metabolism; D037521:Virulence Factors / Q000235:genetics
chemical_list: D001425:Bacterial Outer Membrane Proteins; D012329:RNA, Bacterial; D058727:RNA, Small Untranslated; D000069296:Type III Secretion Systems; D037521:Virulence Factors; C078167:OMPA outer membrane proteins
keywords: Shigella flexneri; response; sRNA; stress tolerance; virulence