{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,20]],"date-time":"2026-03-20T03:29:30Z","timestamp":1773977370628,"version":"3.50.1"},"reference-count":51,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2015,7,1]],"date-time":"2015-07-01T00:00:00Z","timestamp":1435708800000},"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":[[2015,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Bacterial pathogens produce a number of autotransporters that possess diverse functions. These include the family of serine protease autotransporters of\n            <jats:named-content content-type=\"genus-species\">Enterobacteriaceae<\/jats:named-content>\n            (SPATEs) produced by enteric pathogens such as\n            <jats:named-content content-type=\"genus-species\">Shigella flexneri<\/jats:named-content>\n            and enteroaggregative\n            <jats:named-content content-type=\"genus-species\">Escherichia coli<\/jats:named-content>\n            . Of these SPATEs, one termed \u201cprotein involved in colonization,\u201d or Pic, has been shown to possess mucinase activity\n            <jats:italic>in vitro<\/jats:italic>\n            , but to date, its role in\n            <jats:italic>in vivo<\/jats:italic>\n            enteric pathogenesis is unknown. Testing a\n            <jats:italic>pic<\/jats:italic>\n            null (\u0394\n            <jats:italic>picC<\/jats:italic>\n            ) mutant in\n            <jats:named-content content-type=\"genus-species\">Citrobacter rodentium<\/jats:named-content>\n            , a natural mouse pathogen, found that the\n            <jats:named-content content-type=\"genus-species\">C. rodentium<\/jats:named-content>\n            \u0394\n            <jats:italic>picC<\/jats:italic>\n            strain was impaired in its ability to degrade mucin\n            <jats:italic>in vitro<\/jats:italic>\n            compared to the wild type. Upon infection of mice, the \u0394\n            <jats:italic>picC<\/jats:italic>\n            mutant exhibited a hypervirulent phenotype with dramatically heavier pathogen burdens found in intestinal crypts. \u0394\n            <jats:italic>picC<\/jats:italic>\n            mutant-infected mice suffered greater barrier disruption and more severe colitis and weight loss, necessitating their euthanization between 10 and 14 days postinfection. Notably, the virulence of the \u0394\n            <jats:italic>picC<\/jats:italic>\n            mutant was normalized when the\n            <jats:italic>picC<\/jats:italic>\n            gene was restored; however, a PicC point mutant causing loss of mucinase activity did not replicate the \u0394\n            <jats:italic>picC<\/jats:italic>\n            phenotype. Exploring other aspects of PicC function, the \u0394\n            <jats:italic>picC<\/jats:italic>\n            mutant was found to aggregate to higher levels\n            <jats:italic>in vivo<\/jats:italic>\n            than wild-type\n            <jats:named-content content-type=\"genus-species\">C. rodentium<\/jats:named-content>\n            . Moreover, unlike the wild type, the\n            <jats:named-content content-type=\"genus-species\">C. rodentium<\/jats:named-content>\n            \u0394\n            <jats:italic>picC<\/jats:italic>\n            mutant had a red, dry, and rough (RDAR) morphology\n            <jats:italic>in vitro<\/jats:italic>\n            and showed increased activation of the innate receptor Toll-like receptor 2 (TLR2). Interestingly, the\n            <jats:named-content content-type=\"genus-species\">C. rodentium<\/jats:named-content>\n            \u0394\n            <jats:italic>picC<\/jats:italic>\n            mutant caused a degree of pathology similar to that of wild-type\n            <jats:named-content content-type=\"genus-species\">C. rodentium<\/jats:named-content>\n            when infecting TLR2-deficient mice, showing that despite its mucinase activity, PicC's major role\n            <jats:italic>in vivo<\/jats:italic>\n            may be to limit\n            <jats:named-content content-type=\"genus-species\">C. rodentium<\/jats:named-content>\n            's stimulation of the host's innate immune system.\n          <\/jats:p>","DOI":"10.1128\/iai.00025-15","type":"journal-article","created":{"date-parts":[[2015,4,21]],"date-time":"2015-04-21T02:01:57Z","timestamp":1429581717000},"page":"2636-2650","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":28,"title":["The Serine Protease Autotransporter Pic Modulates Citrobacter rodentium Pathogenesis and Its Innate Recognition by the Host"],"prefix":"10.1128","volume":"83","author":[{"given":"Kirandeep","family":"Bhullar","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Child and Family Research Institute, Vancouver, British Columbia, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maryam","family":"Zarepour","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Child and Family Research Institute, Vancouver, British Columbia, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongbing","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Child and Family Research Institute, Vancouver, British Columbia, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Child and Family Research Institute, Vancouver, British Columbia, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew","family":"Croxen","sequence":"additional","affiliation":[{"name":"Michael Smith Laboratories, University of British Columbia, Vancouver, British Columbia, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Stahl","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Gastroenterology, Child and Family Research Institute, Vancouver, British Columbia, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"B. 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