The Shigella flexneri OspB effector: an early immunomodulator

Ambrosi, Cecilia; Pompili, Monica; Scribano, Daniela; Limongi, Dolores; Petrucca, Andrea; Cannavacciuolo, Sonia; Schippa, Serena; Zagaglia, Carlo; Grossi, Milena; Nicoletti, Mauro

doi:10.1016/j.ijmm.2014.11.004

Cited by 25 publications

(26 citation statements)

References 46 publications

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“…OspB is capable of nuclear localization for activation of MAPK signaling pathways. This contributes to inflammation and PMN migration, possibly inducing hepoxilin A3, an arachidonic acid derivative, and apical secretion of IL-8, a PMN chemoattractant (Ambrosi et al, 2014). An ospB − mutant had a 60% decrease in PMN migration and a 30% decrease in ERK1/2 activation 90 min post-infection when compared to wild-type Shigella (Zurawski et al, 2009).…”

Section: Discussionmentioning

confidence: 99%

“…An ospB − mutant had a 60% decrease in PMN migration and a 30% decrease in ERK1/2 activation 90 min post-infection when compared to wild-type Shigella (Zurawski et al, 2009). Furthermore, Ambrosi et al (2014) showed that an ospB − knockout displayed significantly reduced onset and severity of symptoms in the guinea pig keratoconjunctivitis model of infection (Sereny test). However, OspB also activates the master regulator of cell growth mTOR via a direct interaction with the cellular scaffold protein IQGAP1, which also interacts with mTOR activators ERK1/2.…”

Section: Discussionmentioning

confidence: 99%

“…Here the T3SS is activated, and Shigella can produce ShET2 to induce further fluid secretion (Nataro et al, 1995). Other T3SS effectors, including OspB (Zurawski et al, 2009; Ambrosi et al, 2014), OspC1 (Zurawski et al, 2006), and OspZ (Zurawski et al, 2008) (in S. flexneri ) are secreted to phosphorylate and activate MAPK pathways. Consequently, increased apical secretion of the chemoattractant IL-8 causes PMN leukocytes to migrate across the epithelium in a basolateral to apical direction.…”

Section: Discussionmentioning

confidence: 99%

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How Do the Virulence Factors of Shigella Work Together to Cause Disease?

Mattock

Blocker

2017

Front. Cell. Infect. Microbiol.

193

173

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Shigella is the major cause of bacillary dysentery world-wide. It is divided into four species, named S. flexneri, S. sonnei, S. dysenteriae, and S. boydii, which are distinct genomically and in their ability to cause disease. Shigellosis, the clinical presentation of Shigella infection, is characterized by watery diarrhea, abdominal cramps, and fever. Shigella's ability to cause disease has been attributed to virulence factors, which are encoded on chromosomal pathogenicity islands and the virulence plasmid. However, information on these virulence factors is not often brought together to create a detailed picture of infection, and how this translates into shigellosis symptoms. Firstly, Shigella secretes virulence factors that induce severe inflammation and mediate enterotoxic effects on the colon, producing the classic watery diarrhea seen early in infection. Secondly, Shigella injects virulence effectors into epithelial cells via its Type III Secretion System to subvert the host cell structure and function. This allows invasion of epithelial cells, establishing a replicative niche, and causes erratic destruction of the colonic epithelium. Thirdly, Shigella produces effectors to down-regulate inflammation and the innate immune response. This promotes infection and limits the adaptive immune response, causing the host to remain partially susceptible to re-infection. Combinations of these virulence factors may contribute to the different symptoms and infection capabilities of the diverse Shigella species, in addition to distinct transmission patterns. Further investigation of the dominant species causing disease, using whole-genome sequencing and genotyping, will allow comparison and identification of crucial virulence factors and may contribute to the production of a pan-Shigella vaccine.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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How Do the Virulence Factors of Shigella Work Together to Cause Disease?

Mattock

Blocker

2017

Front. Cell. Infect. Microbiol.

193

173

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“…Semi-quantitative real-time PCR (RT-PCR) was performed in the Bio-Rad iQ5 real-time PCR detection system with iQ SYBR Green Supermix (Bio-Rad, Milan, Italy), using the following conditions: 5 min at 95 • C, 40 cycles at 95 • C for 15 s and 60 • C for 30 s. The sequences of the primer pairs used for manX were manXF 5 -GGGCCAAACGACTACATGGTTATT-3 and manXR5 -ACCTGGGTGAGCAGTGTCTTACG-3 , and for the 16S rRNA gene (rrsG), used for data normalization, rrsGF 5 -GGTGTAGCGGTGAAATGCGTAG-3 and rrsGR 5 -TCAAG GGCACAACCTCCAAGTC-3 . To determine the fold change expression of manX in different conditions the 2 −∆∆Ct method was used, as described previously [64], considering the bacteria grown in d-glucose as the reference condition.…”

Section: Expression Levels Of the Manx Permeasementioning

confidence: 99%

“…Equal amounts of WCE were loaded onto 12.5% Tris-glycine SDS-PAGE [65], transferred onto PVDF membranes (GE-Healthcare Bio-Sciences, Rome, Italy) and hybridized using polyclonal anti-ManX antibody (Abmart, Shanghai, China). The outer membrane protein A (OmpA) was used as a protein loading control, as reported elsewhere [64]. Blots were visualized by the enhanced chemiluminescence system (GE-Healthcare Bio-Sciences, Rome, Italy).…”

Section: Expression Levels Of the Manx Permeasementioning

confidence: 99%

d-Mannose Treatment neither Affects Uropathogenic Escherichia coli Properties nor Induces Stable FimH Modifications

et al. 2020

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Urinary tract infections (UTIs) are mainly caused by uropathogenic Escherichia coli (UPEC). Acute and recurrent UTIs are commonly treated with antibiotics, the efficacy of which is limited by the emergence of antibiotic resistant strains. The natural sugar d-mannose is considered as an alternative to antibiotics due to its ability to mask the bacterial adhesin FimH, thereby preventing its binding to urothelial cells. Despite its extensive use, the possibility that d-mannose exerts “antibiotic-like” activity by altering bacterial growth and metabolism or selecting FimH variants has not been investigated yet. To this aim, main bacterial features of the prototype UPEC strain CFT073 treated with d-mannose were analyzed by standard microbiological methods. FimH functionality was analyzed by yeast agglutination and human bladder cell adhesion assays. Our results indicate that high d-mannose concentrations have no effect on bacterial growth and do not interfere with the activity of different antibiotics. d-mannose ranked as the least preferred carbon source to support bacterial metabolism and growth, in comparison with d-glucose, d-fructose, and l-arabinose. Since small glucose amounts are physiologically detectable in urine, we can conclude that the presence of d-mannose is irrelevant for bacterial metabolism. Moreover, d-mannose removal after long-term exposure did not alter FimH’s capacity to bind to mannosylated proteins. Overall, our data indicate that d-mannose is a good alternative in the prevention and treatment of UPEC-related UTIs.

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Shigella: Virulence Factors and Pathogenicity

Bliven

Lampel

2017

Foodborne Pathogens

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The Shigella flexneri OspB effector: an early immunomodulator

Cited by 25 publications

References 46 publications

How Do the Virulence Factors of Shigella Work Together to Cause Disease?

How Do the Virulence Factors of Shigella Work Together to Cause Disease?

d-Mannose Treatment neither Affects Uropathogenic Escherichia coli Properties nor Induces Stable FimH Modifications

Shigella: Virulence Factors and Pathogenicity

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