The VirF21:VirF30 protein ratio is affected by temperature and impacts <i>Shigella flexneri</i> host cell invasion

Skovajsová, Eva; Colonna, Bianca; Prosseda, Gianni; Sellin, Mikael E.; Martino, Maria Letizia Di

doi:10.1093/femsle/fnac043

Cited by 7 publications

(4 citation statements)

References 54 publications

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“…The VirF protein is the master controller of the entire virulence system, and, given its pivotal role, many studies have been focused on its regulation, leading to the characterization of multiple mechanisms that contribute to its stringent regulation ( 15 , 17 – 21 ). VirF is a member of the AraC-XylS family of transcriptional activators, which are characterized by a 99- to 100-amino-acid segment containing two HTH motifs separated by an alpha helix ( 22 – 24 ).…”

Section: Introductionmentioning

confidence: 99%

Fatty Acids Abolish Shigella Virulence by Inhibiting Its Master Regulator, VirF

et al. 2023

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Section: Introductionmentioning

confidence: 99%

Fatty Acids Abolish Shigella Virulence by Inhibiting Its Master Regulator, VirF

et al. 2023

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“…The virF ORF can produce two forms of VirF: VirF 30 (30 kD) and VirF 21 (21 kD) by differential translation. 46 , 47 Therefore, we investigated whether fatty acids mediated the degradation of both these forms of VirF. We observed that VirF 30 was rapidly degraded by the exposure to c2-HDA ( Figure 5b ).…”

Section: Resultsmentioning

confidence: 98%

Shigella flexneri utilizes intestinal signals to control its virulence

Chowdhury,

Bitar,

Bell

et al. 2023

Gut Microbes

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The enteric pathogens have evolved to utilize elements from their surroundings to optimize their infection strategies. A common mechanism to achieve this is to employ intestinal compounds as signals to control the activity of a master regulator of virulence. Shigella flexneri ( S. flexneri ) is a highly infectious entero-invasive pathogen which requires very few organisms to cause invasion of the colonic mucosa. The invasion program is controlled by the virulence master regulator VirF. Here, we show that the fatty acids commonly found in the colon can be exploited by S. flexneri to repress its virulence, allowing it to energetically finance its proliferation, thus increasing its pathogenicity. Colonic fatty acids such as oleic, palmitoleic and cis- 2-hexadecenoic acid were shown to directly bind to VirF and mediate its prompt degradation. These fatty acids also disrupted the ability of VirF to bind to its target DNA, suppressing the transcription of the downstream virulence genes and significantly reducing the invasion of S. flexneri to colonic epithelial cells. Treatment with colonic fatty acids significantly increased the growth rate of the pathogen only under invasion-inducing conditions, showing that the reduction in the burden of virulence promotes a growth advantage. These results demonstrate the process by which S. flexneri can employ intestinal compounds as signals to increase its numbers at its preferred site of invasion, highlighting the mechanism by which the full spectrum of shigellosis is achieved despite a miniscule infectious dose. This highlights an elegant model of environmental adaption by S. flexneri to maximize the pathogenic benefit.

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“…At temperatures similar to those of its host (37 °C), the binding of H-NS to the virF promoter is weakened, thereby allowing the production of the VirF protein [ 72 , 73 ]. A shorter version of VirF (VirF 21 ; MW 21 kDa), generated from an alternative translation initiation codon also contributes to repressing the production of the full-length VirF protein at 30 °C [ 74 , 75 ]. This regulatory mechanism may contribute to maintaining tight control of virulence, but its role in pathogenesis is unknown.…”

Section: The Major Virulence Gene Regulatory Cascade In Shi...mentioning

confidence: 99%

A Tale about Shigella: Evolution, Plasmid, and Virulence

Haidar-Ahmad,

Manigat,

Silué

et al. 2023

Microorganisms

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Shigella spp. cause hundreds of millions of intestinal infections each year. They target the mucosa of the human colon and are an important model of intracellular bacterial pathogenesis. Shigella is a pathovar of Escherichia coli that is characterized by the presence of a large invasion plasmid, pINV, which encodes the characteristic type III secretion system and icsA used for cytosol invasion and cell-to-cell spread, respectively. First, we review recent advances in the genetic aspects of Shigella, shedding light on its evolutionary history within the E. coli lineage and its relationship to the acquisition of pINV. We then discuss recent insights into the processes that allow for the maintenance of pINV. Finally, we describe the role of the transcription activators VirF, VirB, and MxiE in the major virulence gene regulatory cascades that control the expression of the type III secretion system and icsA. This provides an opportunity to examine the interplay between these pINV-encoded transcriptional activators and numerous chromosome-encoded factors that modulate their activity. Finally, we discuss novel chromosomal genes icaR, icaT, and yccE that are regulated by MxiE. This review emphasizes the notion that Shigella and E. coli have walked the fine line between commensalism and pathogenesis for much of their history.

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The VirF21:VirF30 protein ratio is affected by temperature and impacts Shigella flexneri host cell invasion

Cited by 7 publications

References 54 publications

Fatty Acids Abolish Shigella Virulence by Inhibiting Its Master Regulator, VirF

Fatty Acids Abolish Shigella Virulence by Inhibiting Its Master Regulator, VirF

Shigella flexneri utilizes intestinal signals to control its virulence

A Tale about Shigella: Evolution, Plasmid, and Virulence

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