Use of the common marmoset to study Burkholderia mallei infection.

Burkholderia mallei is a host-adapted bacterium that does not persist outside of its equine reservoir. The organism causes the zoonosis glanders, which is endemic in Asia, Africa, the Middle East and South America. Infection by B. mallei typically occurs via the respiratory or percutaneous route, an...

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Main Authors: Tomislav Jelesijevic, Shawn M Zimmerman, Stephen B Harvey, Daniel G Mead, Teresa L Shaffer, D Mark Estes, Frank Michel, Frederick D Quinn, Robert J Hogan, Eric R Lafontaine
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4393281?pdf=render
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author Tomislav Jelesijevic
Shawn M Zimmerman
Stephen B Harvey
Daniel G Mead
Teresa L Shaffer
D Mark Estes
Frank Michel
Frederick D Quinn
Robert J Hogan
Eric R Lafontaine
author_facet Tomislav Jelesijevic
Shawn M Zimmerman
Stephen B Harvey
Daniel G Mead
Teresa L Shaffer
D Mark Estes
Frank Michel
Frederick D Quinn
Robert J Hogan
Eric R Lafontaine
author_sort Tomislav Jelesijevic
collection DOAJ
description Burkholderia mallei is a host-adapted bacterium that does not persist outside of its equine reservoir. The organism causes the zoonosis glanders, which is endemic in Asia, Africa, the Middle East and South America. Infection by B. mallei typically occurs via the respiratory or percutaneous route, and the most common manifestations are life-threatening pneumonia and bacteremia. Glanders is difficult to diagnose and requires prolonged antibiotic therapy with low success rates. There is no vaccine to protect against B. mallei and there is concern regarding its use as a biothreat agent. Thus, experiments were performed to establish a non-human primate model of intranasal infection to study the organism and develop countermeasures. Groups of marmosets (Callithrix jacchus) were inoculated intranasally with B. mallei strain ATCC 23344 and monitored for clinical signs of illness for up to 13 days. We discovered that 83% of marmosets inoculated with doses of 2.5 X 10(4) to 2.5 X 10(5) bacteria developed acute lethal infection within 3-4 days. Signs of disease were severe and included lethargy, inappetence, conjunctivitis, mucopurulent and hemorrhagic nasal discharges, and increased respiratory effort with abdominal lifts. Burkholderia mallei was cultured from the lungs, spleen and liver of these animals, and pathologic examination of tissues revealed lesions characteristic of glanders. Challenge experiments also revealed that 91% of animals infected with doses ranging from 25 to 2.5 X 10(3) bacteria exhibited mild non-specific signs of illness and were culture negative. One marmoset inoculated with 2.5 X 10(3) organisms developed moderate signs of disease and reached humane end-points 8 days post-infection. The liver and spleen of this animal were colonized with the agent and pathological analysis of tissues showed nasal, splenic and hepatic lesions. Taken together, these data indicate that the marmoset is a suitable model to study respiratory infection by B. mallei.
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spelling doaj.art-13d0b487706c4882a38647cd9c8b37572022-12-21T23:27:53ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01104e012418110.1371/journal.pone.0124181Use of the common marmoset to study Burkholderia mallei infection.Tomislav JelesijevicShawn M ZimmermanStephen B HarveyDaniel G MeadTeresa L ShafferD Mark EstesFrank MichelFrederick D QuinnRobert J HoganEric R LafontaineBurkholderia mallei is a host-adapted bacterium that does not persist outside of its equine reservoir. The organism causes the zoonosis glanders, which is endemic in Asia, Africa, the Middle East and South America. Infection by B. mallei typically occurs via the respiratory or percutaneous route, and the most common manifestations are life-threatening pneumonia and bacteremia. Glanders is difficult to diagnose and requires prolonged antibiotic therapy with low success rates. There is no vaccine to protect against B. mallei and there is concern regarding its use as a biothreat agent. Thus, experiments were performed to establish a non-human primate model of intranasal infection to study the organism and develop countermeasures. Groups of marmosets (Callithrix jacchus) were inoculated intranasally with B. mallei strain ATCC 23344 and monitored for clinical signs of illness for up to 13 days. We discovered that 83% of marmosets inoculated with doses of 2.5 X 10(4) to 2.5 X 10(5) bacteria developed acute lethal infection within 3-4 days. Signs of disease were severe and included lethargy, inappetence, conjunctivitis, mucopurulent and hemorrhagic nasal discharges, and increased respiratory effort with abdominal lifts. Burkholderia mallei was cultured from the lungs, spleen and liver of these animals, and pathologic examination of tissues revealed lesions characteristic of glanders. Challenge experiments also revealed that 91% of animals infected with doses ranging from 25 to 2.5 X 10(3) bacteria exhibited mild non-specific signs of illness and were culture negative. One marmoset inoculated with 2.5 X 10(3) organisms developed moderate signs of disease and reached humane end-points 8 days post-infection. The liver and spleen of this animal were colonized with the agent and pathological analysis of tissues showed nasal, splenic and hepatic lesions. Taken together, these data indicate that the marmoset is a suitable model to study respiratory infection by B. mallei.http://europepmc.org/articles/PMC4393281?pdf=render
spellingShingle Tomislav Jelesijevic
Shawn M Zimmerman
Stephen B Harvey
Daniel G Mead
Teresa L Shaffer
D Mark Estes
Frank Michel
Frederick D Quinn
Robert J Hogan
Eric R Lafontaine
Use of the common marmoset to study Burkholderia mallei infection.
PLoS ONE
title Use of the common marmoset to study Burkholderia mallei infection.
title_full Use of the common marmoset to study Burkholderia mallei infection.
title_fullStr Use of the common marmoset to study Burkholderia mallei infection.
title_full_unstemmed Use of the common marmoset to study Burkholderia mallei infection.
title_short Use of the common marmoset to study Burkholderia mallei infection.
title_sort use of the common marmoset to study burkholderia mallei infection
url http://europepmc.org/articles/PMC4393281?pdf=render
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