Dataset Information

Shigellaflexneri Regulator SlyA Controls Bacterial Acid Resistance by Directly Activating the Glutamate Decarboxylation System.

ABSTRACT: Shigella flexneri is an important foodborne bacterial pathogen with infectious dose as low as 10-100 cells. SlyA, a transcriptional regulator of the MarR family, has been shown to regulate virulence in a closely related bacterial pathogen, Salmonella Typhimurium. However, the regulatory role of SlyA in S. flexneri is less understood. Here we applied unbiased proteomic profiling to define the SlyA regulon in S. flexneri. We found that the genetic ablation of slyA led to the alteration of 18 bacterial proteins among over 1400 identifications. Intriguingly, most down-regulated proteins (whose expression is SlyA-dependent) were associated with bacterial acid resistance such as the glutamate decarboxylation system. We further demonstrated that SlyA directly regulates the expression of GadA, a glutamate decarboxylase, by binding to the promotor region of its coding gene. Importantly, overexpression of GadA was able to rescue the survival defect of the ?slyA mutant under acid stress. Therefore, our study highlights a major role of SlyA in controlling S. flexneri acid resistance and provides a molecular mechanism underlying such regulation as well.

SUBMITTER: Zhang B

PROVIDER: S-EPMC6128205 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Shigellaflexneri Regulator SlyA Controls Bacterial Acid Resistance by Directly Activating the Glutamate Decarboxylation System.

Zhang Buyu B Ran Longhao L Wu Mei M Li Zezhou Z Jiang Jiezhang J Wang Zhen Z Cheng Sen S Fu Jiaqi J Liu Xiaoyun X

Frontiers in microbiology 20180831

Shigella flexneri is an important foodborne bacterial pathogen with infectious dose as low as 10-100 cells. SlyA, a transcriptional regulator of the MarR family, has been shown to regulate virulence in a closely related bacterial pathogen, Salmonella Typhimurium. However, the regulatory role of SlyA in S. flexneri is less understood. Here we applied unbiased proteomic profiling to define the SlyA regulon in S. flexneri. We found that the genetic ablation of slyA</i ...[more]

PMID: 30233544

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Project description:VirB is a key regulator of genes located on the large virulence plasmid (pINV) in the bacterial pathogen Shigella flexneri VirB is unusual; it is not related to other transcriptional regulators, instead, it belongs to a family of proteins that primarily function in plasmid and chromosome partitioning; exemplified by ParB. Despite this, VirB does not function to segregate DNA, but rather counters transcriptional silencing mediated by the nucleoid structuring protein, H-NS. Since ParB localizes subcellularly as discrete foci in the bacterial cytoplasm, we chose to investigate the subcellular localization of VirB to gain novel insight into how VirB functions as a transcriptional anti-silencer. To do this, a GFP-VirB fusion that retains the regulatory activity of VirB and yet, does not undergo significant protein degradation in S. flexneri, was used. Surprisingly, discrete fluorescent foci were observed in live wild-type S. flexneri cells and an isogenic virB mutant using fluorescence microscopy. In contrast, foci were rarely observed (<10%) in pINV-cured cells or in cells expressing a GFP-VirB fusion carrying amino acid substitutions in the VirB DNA binding domain. Finally, the 25 bp VirB-binding site was demonstrated to be sufficient and necessary for GFP-VirB focus formation using a set of small surrogate plasmids. Combined, these data demonstrate that the VirB:DNA interactions required for the transcriptional anti-silencing activity of VirB on pINV are a prerequisite for the subcellular localization of VirB in the bacterial cytoplasm. The significance of these findings, in light of the anti-silencing activity of VirB, is discussed.ImportanceThis study reveals the subcellular localization of VirB, a key transcriptional regulator of virulence genes found on the large virulence plasmid (pINV) in Shigella. Fluorescent signals generated by an active GFP-VirB fusion form 2, 3, or 4 discrete foci in the bacterial cytoplasm, predominantly at the quarter cell position. These signals are completely dependent upon VirB interacting with its DNA binding site found either on the virulence plasmid or an engineered surrogate. Our findings: 1) provide novel insight into VirB:pINV interactions, 2) suggest that VirB may have utility as a DNA marker, and 3) raise questions about how and why this anti-silencing protein that controls virulence gene expression on pINV of Shigella spp. forms discrete foci/hubs within the bacterial cytoplasm.

Dataset Information

Shigellaflexneri Regulator SlyA Controls Bacterial Acid Resistance by Directly Activating the Glutamate Decarboxylation System.

Publications

<i>Shigella</i><i>flexneri</i> Regulator SlyA Controls Bacterial Acid Resistance by Directly Activating the Glutamate Decarboxylation System.

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