The synthesis of OspD3 (ShET2) in<i>Shigella flexneri</i>is independent of OspC1

Faherty, Christina S.; Wu, Tao; Morris, Carolyn R.; Grassel, Christen; Rasko, David A.; Harper, Jill M.; Shea‐Donohue, Terez; Fasano, Alessio; Barry, Eileen M.

doi:10.1080/19490976.2016.1239682

Cited by 14 publications

(19 citation statements)

References 48 publications

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“…OspD1 has a unique role in regulating type III secretion not shared with OspD2 and OspD3 (Parsot et al, 2005), but redundancy in their effector function(s) is unknown. Unlike ShET1, ShET2 secretion is dependent on the T3SS (Farfán et al, 2011) but how this is regulated unclear (Faherty et al, 2016). The ospD3 − (ShET2) knockout has similar effects in Using chamber experiments to a set1AB − (ShET1) knockout, with reduced I sc increase in comparison to the wild-type strain (Nataro et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

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

Mattock

Blocker

2017

Front. Cell. Infect. Microbiol.

196

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%

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

Mattock

Blocker

2017

Front. Cell. Infect. Microbiol.

196

173

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“…RNA was isolated from the bacterial cultures as previously described (85) with Qiagen RNeasy kits. DNA was digested with Turbo DNase (Invitrogen), and the concentrations of total RNA were determined using a NanoDrop ND-1000 spectrophotometer.…”

Section: Methodsmentioning

confidence: 99%

Shigella flexneri Adherence Factor Expression in In Vivo -Like Conditions

Chanin

Nickerson

Llanos-Chea

et al. 2019

mSphere

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Bacterial pathogens have evolved to regulate virulence gene expression at critical points in the colonization and infection processes to successfully cause disease. The Shigella species infect the epithelial cells lining the colon to result in millions of cases of diarrhea and a significant global health burden. As antibiotic resistance rates increase, understanding the mechanisms of infection is vital to ensure successful vaccine development. Despite significant gains in our understanding of Shigella infection, it remains unknown how the bacteria initiate contact with the colonic epithelium. Most pathogens harbor multiple adherence factors to facilitate this process, but Shigella was thought to have lost the ability to produce these factors. Interestingly, we have identified conditions that mimic some features of gastrointestinal transit and that enable Shigella to express adherence structural genes. This work highlights aspects of genetic regulation for Shigella adherence factors and may have a significant impact on future vaccine development.

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“…RNA was isolated from bacterial cultures as previously described (84) with Qiagen’s RNeasy kits. DNA was digested with Turbo DNase (Invitrogen), and concentrations of total RNA were determined using a NanoDrop ND-1000 spectrophotometer.…”

Section: Methodsmentioning

confidence: 99%

“…For quantitative RT-PCR analysis (qRT-PCR), biologically independent RNA samples were isolated and ensured DNA-free as described above. Analysis by qRT-PCR was performed as previously described (84), and all data were normalized to levels of rpoA and analyzed using the comparative cycle threshold (ΔC T ) method (87). The expression levels of the target genes under the various conditions were compared using the relative quantification method (87).…”

Section: Methodsmentioning

confidence: 99%

Shigella flexneri adherence factor expression in in vivo-like conditions

Chanin

Nickerson

Llanos-Chea

et al. 2019

Preprint

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26The Shigella species are Gram-negative, facultative intracellular pathogens that invade the 27 colonic epithelium and cause significant diarrheal disease. Despite extensive research on the pathogen, 28 comprehensive understanding of how Shigella initiates contact with epithelial cells remains unknown. 29 Shigella maintains many of the same Escherichia coli adherence gene operons; however, at least one 30 critical gene component in each operon is currently annotated as a pseudogene in reference genomes. 31 These annotations, coupled with a lack of structures upon microscopic analysis following growth in 32 laboratory media, have led the field to hypothesize that Shigella is unable to produce fimbriae or other 33 "traditional" adherence factors. Nevertheless, our previous analyses have demonstrated that a 34 combination of bile salts and glucose induce both biofilm formation and adherence to colonic epithelial 35 cells. Through a two-part investigation, we first utilized various transcriptomic analyses to demonstrate 36 that S. flexneri strain 2457T adherence gene operons are transcribed. Subsequently, we performed 37 mutation, electron microscopy, biofilm, infection, and proteomic analyses to characterize three of the 38 structural genes. In combination, these studies demonstrate that despite the gene annotations, S. 39 flexneri 2457T uses adherence factors to initiate biofilm formation as well as epithelial cell contact. 40 Furthermore, host factors, namely glucose and bile salts in the small intestine, offer key environmental 41 stimuli required for proper adherence factor expression in S. flexneri. This research may have a 42 significant impact on vaccine development for Shigella and further highlights the importance of 43 utilizing in vivo-like conditions to study bacterial pathogenesis. 44 45 Importance 46 Bacterial pathogens have evolved to regulate virulence gene expression at critical points in the 47 colonization and infection processes to successfully cause disease. The Shigella species infect the 48 epithelial cells lining the colon to result in millions of cases of diarrhea and a significant global health 49 burden. As antibiotic resistance rates increase, understanding the mechanisms of infection are vital to 50 3 ensure successful vaccine development. Despite significant gains in our understanding of Shigella 51 infection, it remains unknown how the bacteria initiate contact with the colonic epithelium. Most 52 pathogens harbor multiple adherence factors to facilitate this process, but Shigella was thought to have 53 lost the ability to produce these factors. Interestingly, we have identified conditions that mimic some 54 features of gastrointestinal transit and enable Shigella to express adherence factors. This work 55 highlights aspects of genetic regulation for Shigella adherence factors and may have a significant 56 impact on future vaccine development. 57 58 59Shigella flexneri is a Gram-negative, facultative anaerobe that infects millions of people each 60 year by causing water...

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The synthesis of OspD3 (ShET2) inShigella flexneriis independent of OspC1

Cited by 14 publications

References 48 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?

Shigella flexneri Adherence Factor Expression in In Vivo -Like Conditions

Shigella flexneri adherence factor expression in in vivo-like conditions

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