An adhesion protein of
            <i>Salmonella enterica</i>
            serovar Typhi is required for pathogenesis and potential target for vaccine development

Ghosh, Shubhamoy; Chakraborty, Krishnendu; Theeya, Nagaraja; Basak, Surajit; Koley, Hemanta; Dutta, Shanta; Mitra, U; Das, Santasabuj

doi:10.1073/pnas.1016180108

Cited by 60 publications

(59 citation statements)

References 43 publications

(48 reference statements)

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“…Since the number of intracellular bacteria increased progressively with time until 24 h following infection, we adjusted for its contribution to the increase in T4519 expression by calculating the ratio of the expression of t4519 mRNA to that of the housekeeping gene 16S rRNA and the ratio of T4519 protein expression to T2544 protein expression. T2544 is a noninducible outer membrane protein expressed by various strains of S. Typhi, including Ty2 (20). However, T4519 expression was not induced in intestinal epithelial cells (IECs) (data not shown).…”

Section: Resultsmentioning

confidence: 99%

“…To explore the role of T4519 in bacterial pathogenesis in vivo, we used an iron overload mouse model (20). BALB/c mice infected orally with Ty2 or the complemented (␣-Ty2⌬t4519) strain at 5 times the LD 50 showed 100% mortality within 7 days.…”

Section: Resultsmentioning

confidence: 99%

“…All animal experiments were carried out according to the protocols approved by the Institutional Animal Ethics Committee, National Institute of Cholera and Enteric Diseases (NICED), Kolkata, India. An iron overload mouse model was used for oral S. Typhi infection as described previously (20). Briefly, BALB/c mice were intraperitoneally (i.p.)…”

Section: Org) the Serine/ Threonine Kinase (Stk) Active-site Signatumentioning

confidence: 99%

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An Inducible and Secreted Eukaryote-Like Serine/Threonine Kinase of Salmonella enterica Serovar Typhi Promotes Intracellular Survival and Pathogenesis

Theeya

Das

et al. 2015

Infect Immun

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e Eukaryote-like serine/threonine kinases (eSTKs) constitute an important family of bacterial virulence factors. Genome analysis had predicted putative eSTKs in Salmonella enterica serovar Typhi, although their functional characterization and the elucidation of their role in pathogenesis are still awaited. We show here that the primary sequence and secondary structure of the t4519 locus of Salmonella Typhi Ty2 have all the signatures of eukaryotic superfamily kinases. t4519 encodes a ϳ39-kDa protein (T4519), which shows serine/threonine kinase activities in vitro. Recombinant T4519 (rT4519) is autophosphorylated and phosphorylates the universal substrate myelin basic protein. Infection of macrophages results in decreased viability of the mutant (Ty2⌬t4519) strain, which is reversed by gene complementation. Moreover, reactive oxygen species produced by the macrophages signal to the bacteria to induce T4519, which is translocated to the host cell cytoplasm. That T4519 may target a host substrate(s) is further supported by the activation of host cellular signaling pathways and the induction of cytokines/chemokines. Finally, the role of T4519 in the pathogenesis of Salmonella Typhi is underscored by the significantly decreased mortality of mice infected with the Ty2⌬t4519 strain and the fact that the competitive index of this strain for causing systemic infection is 0.25% that of the wild-type strain. This study characterizes the first eSTK of Salmonella Typhi and demonstrates its role in promoting phagosomal survival of the bacteria within macrophages, which is a key determinant of pathogenesis. This, to the best of our knowledge, is the first study to describe the essential role of eSTKs in the in vivo pathogenesis of Salmonella spp.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Org) the Serine/ Threonine Kinase (Stk) Active-site Signatumentioning

confidence: 99%

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An Inducible and Secreted Eukaryote-Like Serine/Threonine Kinase of Salmonella enterica Serovar Typhi Promotes Intracellular Survival and Pathogenesis

Theeya

Das

et al. 2015

Infect Immun

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“…Vaccination along with other control measures is currently being used in poultry industry to reduce the zoonotic risk (Desin et al, 2013). In last few years, vaccine control strategic programmes were in search of a suitable strong immunogenic vaccine candidate, this lead to an extensive study on outer membrane proteins of Salmonella (Hamid and Jain, 2008;Ghosh et al, 2011). Outer membrane proteins are good surface immunogens (Nandakumar et al, 1993), and are used in several studies to investigate the capability as a vaccine candidate in poultry (Meenakshi et al, 1999;Khan et al, 2003;Okamura et al, 2012;Prejit et al, 2013).…”

Section: Issn: 2319-7706 Volume 7 Number 05 (2018)mentioning

confidence: 99%

Cloning, Sequencing and In Silico Characterization of OmpF Protein of Salmonella typhimurium for its Immune-Potential

Soman¹,

jit²,

Pratheesh³

et al. 2018

Int.J.Curr.Microbiol.App.Sci

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“…Vaccination is one of the most effective methods of controlling infectious diseases including typhoid, especially protecting the population living in endemic zones [67,68]. Currently two licensed vaccines against Salmonella are in use globally: Vi polysaccharide vaccine and Ty21a live attenuated vaccine [69].…”

Section: Vaccinesmentioning

confidence: 99%

Vi antigen of Salmonella enetrica serovar Typhi — biosynthesis, regulation and its use as vaccine candidate

Kaur

Jain

2012

Open Life Sciences

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Vi capsular polysaccharide (Vi antigen) was first identified as the virulence antigen of Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever in humans. The presence of Vi antigen differentiates S. Typhi from other serovars of Salmonella. Vi antigen is a linear polymer consisting of α-1,4-linked-N-acetyl-galactosaminuronate, whose expression is controlled by three chromosomal loci, namely viaA, viaB and ompB. Both viaA and viaB region are present on Salmonella Pathogenicity Island-7, a large, mosaic, genetic island. The viaA region encodes a positive regulator and the viaB locus is composed of 11 genes designated tviA-tviE (for Vi biosyhthesis), vexA-vexE (for Vi antigen export) and ORF 11. Vi polysaccharide is synthesized from UDP-N-acetyl glucosamine in a series of steps requiring TviB, TviC, and TviE, and regulation of Vi polysaccharide synthesis is controlled by two regulatory systems, rscB-rscC (viaA locus) and ompR-envZ (ompB locus), which respond to changes in osmolarity. This antigen is highly immunogenic and has been used for the formulation of one of the currently available vaccines against typhoid. Despite advancement in the area of vaccinology, its pace of progress needs to be accelerated and effective control programmes will be needed for proper disease management.

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An adhesion protein of Salmonella enterica serovar Typhi is required for pathogenesis and potential target for vaccine development

Cited by 60 publications

References 43 publications

An Inducible and Secreted Eukaryote-Like Serine/Threonine Kinase of Salmonella enterica Serovar Typhi Promotes Intracellular Survival and Pathogenesis

An Inducible and Secreted Eukaryote-Like Serine/Threonine Kinase of Salmonella enterica Serovar Typhi Promotes Intracellular Survival and Pathogenesis

Cloning, Sequencing and In Silico Characterization of OmpF Protein of Salmonella typhimurium for its Immune-Potential

Vi antigen of Salmonella enetrica serovar Typhi — biosynthesis, regulation and its use as vaccine candidate

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