{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T13:23:09Z","timestamp":1790947389211,"version":"4.1.0"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"2","license":[{"start":{"date-parts":[[2014,4,15]],"date-time":"2014-04-15T00:00:00Z","timestamp":1397520000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0\/"},{"start":{"date-parts":[[2014,5,1]],"date-time":"2014-05-01T00:00:00Z","timestamp":1398902400000},"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":["mBio"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Melioidosis is a potentially fatal disease that is endemic to tropical northern Australia and Southeast Asia, with a mortality rate of 14 to 50%. The bacterium\n            <jats:named-content content-type=\"genus-species\">Burkholderia pseudomallei<\/jats:named-content>\n            is the causative agent which infects numerous parts of the human body, including the brain, which results in the neurological manifestation of melioidosis. The olfactory nerve constitutes a direct conduit from the nasal cavity into the brain, and we have previously reported that\n            <jats:named-content content-type=\"genus-species\">B. pseudomallei<\/jats:named-content>\n            can colonize this nerve in mice. We have now investigated in detail the mechanism by which the bacteria penetrate the olfactory and trigeminal nerves within the nasal cavity and infect the brain. We found that the olfactory epithelium responded to intranasal\n            <jats:named-content content-type=\"genus-species\">B. pseudomallei<\/jats:named-content>\n            infection by widespread crenellation followed by disintegration of the neuronal layer to expose the underlying basal layer, which the bacteria then colonized. With the loss of the neuronal cell bodies, olfactory axons also degenerated, and the bacteria then migrated through the now-open conduit of the olfactory nerves. Using immunohistochemistry, we demonstrated that\n            <jats:named-content content-type=\"genus-species\">B. pseudomallei<\/jats:named-content>\n            migrated through the cribriform plate via the olfactory nerves to enter the outer layer of the olfactory bulb in the brain within 24\u00a0h. We also found that the bacteria colonized the thin respiratory epithelium in the nasal cavity and then rapidly migrated along the underlying trigeminal nerve to penetrate the cranial cavity. These results demonstrate that\n            <jats:named-content content-type=\"genus-species\">B. pseudomallei<\/jats:named-content>\n            invasion of the nerves of the nasal cavity leads to direct infection of the brain and bypasses the blood-brain barrier.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>IMPORTANCE<\/jats:bold>\n            Melioidosis is a potentially fatal tropical disease that is endemic to northern Australia and Southeast Asia. It is caused by the bacterium\n            <jats:named-content content-type=\"genus-species\">Burkholderia pseudomallei<\/jats:named-content>\n            , which can infect many organs of the body, including the brain, and results in neurological symptoms. The pathway by which the bacteria can penetrate the brain is unknown, and we have investigated the ability of the bacteria to migrate along nerves that innervate the nasal cavity and enter the frontal region of the brain by using a mouse model of infection. By generating a mutant strain of\n            <jats:named-content content-type=\"genus-species\">B. pseudomallei<\/jats:named-content>\n            which is unable to survive in the blood, we show that the bacteria rapidly penetrate the cranial cavity using the olfactory (smell) nerve and the trigeminal (sensory) nerve that line the nasal cavity.\n          <\/jats:p>","DOI":"10.1128\/mbio.00025-14","type":"journal-article","created":{"date-parts":[[2014,4,16]],"date-time":"2014-04-16T04:13:49Z","timestamp":1397621629000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":64,"title":["Burkholderia pseudomallei Penetrates the Brain via Destruction of the Olfactory and Trigeminal Nerves: Implications for the Pathogenesis of Neurological Melioidosis"],"prefix":"10.1128","volume":"5","author":[{"given":"James A.","family":"St. John","sequence":"first","affiliation":[{"name":"Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny A. K.","family":"Ekberg","sequence":"additional","affiliation":[{"name":"Eskitis Institute for Drug Discovery, Griffith University, Brisbane, Queensland, Australia"},{"name":"School of Biomedical Sciences, Queensland University of Technology, Brisbane, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samantha J.","family":"Dando","sequence":"additional","affiliation":[{"name":"Institute for Glycomics, Griffith University, Gold Coast, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrian C. 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