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.

Principal Component Analysis for Clustering Probiotic-Fortified Beverage Matrices Efficient in Elimination of Shigella sp.

“…Our results corroborate the previous results of Bagamboula et al (2002), which established the survival of S. flexneri in highly acidic apple juice for 14 days [42]. The lag in pathogen inhibition could also be due to the hfq protein in S. flexneri, acting as a key factor in maximal adaptation to environmental stress-especially low pH conditions-thereby regulating acid stress tolerance within the matrix environment [43]. To distinctively discriminate the pathogen clearance ability of the probiotic fortified matrices, we carried out a Principal Component Analysis (PCA) based on their anti-Shigella potential during shelf storage.…”

Global Screening of Salmonella enterica Serovar Typhimurium Genes for Desiccation Survival

“…In Francisella novicida , Hfq protein has an important role in resistance to stresses such as, osmotic change, low pH, heat shock and oxidative stress. Salmonella Hfq protein positively regulates virulence by targeting hilD mRNA that affects secretion of type III secretion system (T3SS) encoded by Salmonella pathogenicity island 1 (SPI-1) (Shakhnovich et al, 2009 ; Yang et al, 2015 ). SPI-2 genes ( ssaHIJ ) encoding T3SS were also required for desiccation survival of Salmonella .…”

Role of the virulence plasmid in acid resistance of Shigella flexneri

“…A 1-ml aliquot of culture was then centrifuged for 5 min at 2000 ×  g , and the resulting pellet resuspended in 1 ml of LB medium adjusted to either pH 2.5 or pH 5.02728. The suspension was then incubated for 30 min at 37 °C with shaking at 220 rpm.…”