title: hfq regulates acid tolerance and virulence by responding to acid stress in Shigella flexneri.
abstract: Shigella flexneri is an important etiological agent of bacillary dysentery in developing countries. The Hfq protein is thought to play a major regulatory role in various cellular processes in this organism. However, the roles of Hfq in stress tolerance and virulence in S. flexneri in response to environmental stress have not been fully studied. In this study, hfq was highly expressed when S. flexneri was exposed to low pH. Growth retardation was observed in the hfq deletion mutant at pH values ranging from 5.0 to 7.0 and the survival rate of the mutant strain was reduced by 60% in acidic conditions (pH 3.0) compared with the wild-type strain. Additionally, competitive invasion assays in HeLa cells and lung invasion assays showed that the virulence of the hfq deletion mutant was significantly decreased. An evaluation of the mechanism revealed that, along with the expression of the Type III secretion system genes, acid resistance genes were also increased with acid stress. Interestingly, a statistically strong linear correlation was observed between the expression of hfq and Type III secretion system genes, as well as between hfq and acid resistance genes, under various pH conditions. In this study, we provide evidence that Hfq regulates genes related to acid resistance for survival under acid stress and controls virulence through the positive regulation of Type III secretion systems. Importantly, we propose that hfq is a key factor in maximal adaptation to host acid stress during infection, regulating acid stress tolerance and virulence in response to acid stress in S. flexneri.
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dong-Da-Jie Street, Fengtai District, Beijing 100071, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dong-Da-Jie Street, Fengtai District, Beijing 100071, China; Institute of Basic Medical Sciences, 27 Tai-Ping-Lu Street, Haidian District, Beijing 100850, China.
authors.forename: Ligui
authors.initials: L
authors.lastname: Wang
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dong-Da-Jie Street, Fengtai District, Beijing 100071, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dong-Da-Jie Street, Fengtai District, Beijing 100071, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Li
authors.affiliation: Clinical Diagnostic Center, 302 Hospital of PLA, 100 Xi-Si-Huan-Zhong-Lu Street, Fengtai District, Beijing 100039, China.
authors.forename: Jiangong
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dong-Da-Jie Street, Fengtai District, Beijing 100071, China.
authors.forename: Shaofu
authors.initials: S
authors.lastname: Qiu
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dong-Da-Jie Street, Fengtai District, Beijing 100071, China.
authors.forename: Rongzhang
authors.initials: R
authors.lastname: Hao
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dong-Da-Jie Street, Fengtai District, Beijing 100071, China.
authors.forename: Zhihao
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Institute of Basic Medical Sciences, 27 Tai-Ping-Lu Street, Haidian District, Beijing 100850, China. Electronic address: liwj@nic.bmi.ac.cn.
authors.forename: Wuju
authors.initials: W
authors.lastname: Li
authors.affiliation: Institute of Disease Control and Prevention, Academy of Military Medical Sciences, 20 Dong-Da-Jie Street, Fengtai District, Beijing 100071, China. Electronic address: hongbinsong@263.net.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Song
mesh_terms: D015964:Gene Expression Regulation, Bacterial; D006367:HeLa Cells; D035001:Host Factor 1 Protein / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009154:Mutation; D012763:Shigella flexneri / Q000235:genetics / Q000254:growth & development / Q000378:metabolism* / Q000472:pathogenicity*; D013312:Stress, Physiological; D000069296:Type III Secretion Systems / Q000235:genetics; D014774:Virulence / Q000235:genetics
chemical_list: D035001:Host Factor 1 Protein; D000069296:Type III Secretion Systems
keywords: Acid tolerance; Shigella flexneri; Virulence; hfq