Burkholderia pseudomallei penetrates the brain via destruction of the olfactory and trigeminal nerves: Implications for the pathogenesis of neurological melioidosis

James A. St John, Jenny A K Ekberg, Samantha J. Dando, Adrian C B Meedeniya, Rachel E. Horton, Michael Batzloff, Suzzanne J. Owen, Stephanie Holt, Ian R. Peak, Glen C. Ulett, Alan Mackay-Sim, Ifor R. Beacham

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28 Citations (Scopus)

Abstract

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 Burkholderia pseudomallei 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 B. pseudomallei 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 B. pseudomallei 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 B. pseudomallei migrated through the cribriform plate via the olfactory nerves to enter the outer layer of the olfactory bulb in the brain within 24 h. 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 B. pseudomallei invasion of the nerves of the nasal cavity leads to direct infection of the brain and bypasses the blood-brain barrier.

Original languageEnglish
Article numbere00025-14
JournalmBio
Volume5
Issue number2
DOIs
Publication statusPublished - 15 Apr 2014
Externally publishedYes

Fingerprint

Melioidosis
Olfactory Nerve
Burkholderia pseudomallei
Trigeminal Nerve
Nasal Cavity
Bacteria
Brain
Burkholderia Infections
Northern Asia
Ethmoid Bone
Olfactory Mucosa
Endemic Diseases
Respiratory Mucosa
Southeastern Asia
Olfactory Bulb
Neurologic Manifestations
Blood-Brain Barrier
Human Body
Axons
Immunohistochemistry

Cite this

St John, J. A., Ekberg, J. A. K., Dando, S. J., Meedeniya, A. C. B., Horton, R. E., Batzloff, M., ... Beacham, I. R. (2014). Burkholderia pseudomallei penetrates the brain via destruction of the olfactory and trigeminal nerves: Implications for the pathogenesis of neurological melioidosis. mBio, 5(2), [e00025-14]. https://doi.org/10.1128/mBio.00025-14
St John, James A. ; Ekberg, Jenny A K ; Dando, Samantha J. ; Meedeniya, Adrian C B ; Horton, Rachel E. ; Batzloff, Michael ; Owen, Suzzanne J. ; Holt, Stephanie ; Peak, Ian R. ; Ulett, Glen C. ; Mackay-Sim, Alan ; Beacham, Ifor R. / Burkholderia pseudomallei penetrates the brain via destruction of the olfactory and trigeminal nerves : Implications for the pathogenesis of neurological melioidosis. In: mBio. 2014 ; Vol. 5, No. 2.
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abstract = "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 Burkholderia pseudomallei 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 B. pseudomallei 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 B. pseudomallei 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 B. pseudomallei migrated through the cribriform plate via the olfactory nerves to enter the outer layer of the olfactory bulb in the brain within 24 h. 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 B. pseudomallei invasion of the nerves of the nasal cavity leads to direct infection of the brain and bypasses the blood-brain barrier.",
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St John, JA, Ekberg, JAK, Dando, SJ, Meedeniya, ACB, Horton, RE, Batzloff, M, Owen, SJ, Holt, S, Peak, IR, Ulett, GC, Mackay-Sim, A & Beacham, IR 2014, 'Burkholderia pseudomallei penetrates the brain via destruction of the olfactory and trigeminal nerves: Implications for the pathogenesis of neurological melioidosis' mBio, vol. 5, no. 2, e00025-14. https://doi.org/10.1128/mBio.00025-14

Burkholderia pseudomallei penetrates the brain via destruction of the olfactory and trigeminal nerves : Implications for the pathogenesis of neurological melioidosis. / St John, James A.; Ekberg, Jenny A K; Dando, Samantha J.; Meedeniya, Adrian C B; Horton, Rachel E.; Batzloff, Michael; Owen, Suzzanne J.; Holt, Stephanie; Peak, Ian R.; Ulett, Glen C.; Mackay-Sim, Alan; Beacham, Ifor R.

In: mBio, Vol. 5, No. 2, e00025-14, 15.04.2014.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Burkholderia pseudomallei penetrates the brain via destruction of the olfactory and trigeminal nerves

T2 - Implications for the pathogenesis of neurological melioidosis

AU - St John, James A.

AU - Ekberg, Jenny A K

AU - Dando, Samantha J.

AU - Meedeniya, Adrian C B

AU - Horton, Rachel E.

AU - Batzloff, Michael

AU - Owen, Suzzanne J.

AU - Holt, Stephanie

AU - Peak, Ian R.

AU - Ulett, Glen C.

AU - Mackay-Sim, Alan

AU - Beacham, Ifor R.

PY - 2014/4/15

Y1 - 2014/4/15

N2 - 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 Burkholderia pseudomallei 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 B. pseudomallei 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 B. pseudomallei 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 B. pseudomallei migrated through the cribriform plate via the olfactory nerves to enter the outer layer of the olfactory bulb in the brain within 24 h. 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 B. pseudomallei invasion of the nerves of the nasal cavity leads to direct infection of the brain and bypasses the blood-brain barrier.

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DO - 10.1128/mBio.00025-14

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