{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T01:52:49Z","timestamp":1791165169482,"version":"4.1.0"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2015,2,1]],"date-time":"2015-02-01T00:00:00Z","timestamp":1422748800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Infect Immun"],"published-print":{"date-parts":[[2015,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Eukaryote-like serine\/threonine kinases (eSTKs) constitute an important family of bacterial virulence factors. Genome analysis had predicted putative eSTKs in\n            <jats:named-content content-type=\"genus-species\">Salmonella enterica<\/jats:named-content>\n            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\n            <jats:italic>t4519<\/jats:italic>\n            locus of\n            <jats:named-content content-type=\"genus-species\">Salmonella<\/jats:named-content>\n            Typhi Ty2 have all the signatures of eukaryotic superfamily kinases.\n            <jats:italic>t4519<\/jats:italic>\n            encodes a \u223c39-kDa protein (T4519), which shows serine\/threonine kinase activities\n            <jats:italic>in vitro<\/jats:italic>\n            . Recombinant T4519 (rT4519) is autophosphorylated and phosphorylates the universal substrate myelin basic protein. Infection of macrophages results in decreased viability of the mutant (Ty2\u0394\n            <jats:italic>t4519<\/jats:italic>\n            ) 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\n            <jats:named-content content-type=\"genus-species\">Salmonella<\/jats:named-content>\n            Typhi is underscored by the significantly decreased mortality of mice infected with the Ty2\u0394\n            <jats:italic>t4519<\/jats:italic>\n            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\n            <jats:named-content content-type=\"genus-species\">Salmonella<\/jats:named-content>\n            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\n            <jats:italic>in vivo<\/jats:italic>\n            pathogenesis of\n            <jats:named-content content-type=\"genus-species\">Salmonella<\/jats:named-content>\n            spp.\n          <\/jats:p>","DOI":"10.1128\/iai.02521-14","type":"journal-article","created":{"date-parts":[[2014,11,18]],"date-time":"2014-11-18T05:15:52Z","timestamp":1416287752000},"page":"522-533","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":11,"title":["An Inducible and Secreted Eukaryote-Like Serine\/Threonine Kinase of Salmonella enterica Serovar Typhi Promotes Intracellular Survival and Pathogenesis"],"prefix":"10.1128","volume":"83","author":[{"given":"Nagaraja","family":"Theeya","sequence":"first","affiliation":[{"name":"Division of Clinical Medicine, National Institute of Cholera and Enteric Diseases, Kolkata, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atri","family":"Ta","sequence":"additional","affiliation":[{"name":"Division of Clinical Medicine, National Institute of Cholera and Enteric Diseases, Kolkata, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sayan","family":"Das","sequence":"additional","affiliation":[{"name":"Division of Clinical Medicine, National Institute of Cholera and Enteric Diseases, Kolkata, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul S.","family":"Mandal","sequence":"additional","affiliation":[{"name":"Biomedical Informatics Centre, National Institute of Cholera and Enteric Diseases, Kolkata, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oishee","family":"Chakrabarti","sequence":"additional","affiliation":[{"name":"Biophysics and Structural Genomics Division, Saha Institute of Nuclear Physics, Kolkata, 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