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Use of a safe, reproducible, and rapid aerosol delivery method to study infection by Burkholderia pseudomallei and Burkholderia mallei in mice.
PLoS One. 2013; 8(10):e76804.Plos

Abstract

Burkholderia pseudomallei, the etiologic agent of melioidosis, is a saprophytic bacterium readily isolated from wet soils of countries bordering the equator. Burkholderia mallei is a host-adapted clone of B. pseudomallei that does not persist outside of its equine reservoir and causes the zoonosis glanders, which is endemic in Asia, Africa, the Middle East and South America. Infection by these organisms typically occurs via percutaneous inoculation or inhalation of aerosols, and the most common manifestation is severe pneumonia leading to fatal bacteremia. Glanders and melioidosis are difficult to diagnose and require prolonged antibiotic therapy with low success rates. There are no vaccines available to protect against either Burkholderia species, and there is concern regarding their use as biological warfare agents given that B. mallei has previously been utilized in this manner. Hence, experiments were performed to establish a mouse model of aerosol infection to study the organisms and develop countermeasures. Using a hand-held aerosolizer, BALB/c mice were inoculated intratracheally with strains B. pseudomallei 1026b and B. mallei ATCC23344 and growth of the agents in the lungs, as well as dissemination to the spleen, were examined. Mice infected with 10(2), 10(3) and 10(4) organisms were unable to control growth of B. mallei in the lungs and bacteria rapidly disseminated to the spleen. Though similar results were observed in mice inoculated with 10(3) and 10(4) B. pseudomallei cells, animals infected with 10(2) organisms controlled bacterial replication in the lungs, dissemination to the spleen, and the extent of bacteremia. Analysis of sera from mice surviving acute infection revealed that animals produced antibodies against antigens known to be targets of the immune response in humans. Taken together, these data show that small volume aerosol inoculation of mice results in acute disease, dose-dependent chronic infection, and immune responses that correlate with those seen in human infections.

Authors+Show Affiliations

Department of Infectious Diseases, University of Georgia, Athens, Georgia, United States of America.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24098563

Citation

Lafontaine, Eric R., et al. "Use of a Safe, Reproducible, and Rapid Aerosol Delivery Method to Study Infection By Burkholderia Pseudomallei and Burkholderia Mallei in Mice." PloS One, vol. 8, no. 10, 2013, pp. e76804.
Lafontaine ER, Zimmerman SM, Shaffer TL, et al. Use of a safe, reproducible, and rapid aerosol delivery method to study infection by Burkholderia pseudomallei and Burkholderia mallei in mice. PLoS One. 2013;8(10):e76804.
Lafontaine, E. R., Zimmerman, S. M., Shaffer, T. L., Michel, F., Gao, X., & Hogan, R. J. (2013). Use of a safe, reproducible, and rapid aerosol delivery method to study infection by Burkholderia pseudomallei and Burkholderia mallei in mice. PloS One, 8(10), e76804. https://doi.org/10.1371/journal.pone.0076804
Lafontaine ER, et al. Use of a Safe, Reproducible, and Rapid Aerosol Delivery Method to Study Infection By Burkholderia Pseudomallei and Burkholderia Mallei in Mice. PLoS One. 2013;8(10):e76804. PubMed PMID: 24098563.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Use of a safe, reproducible, and rapid aerosol delivery method to study infection by Burkholderia pseudomallei and Burkholderia mallei in mice. AU - Lafontaine,Eric R, AU - Zimmerman,Shawn M, AU - Shaffer,Teresa L, AU - Michel,Frank, AU - Gao,Xiudan, AU - Hogan,Robert J, Y1 - 2013/10/02/ PY - 2013/06/26/received PY - 2013/08/26/accepted PY - 2013/10/8/entrez PY - 2013/10/8/pubmed PY - 2014/4/30/medline SP - e76804 EP - e76804 JF - PloS one JO - PLoS One VL - 8 IS - 10 N2 - Burkholderia pseudomallei, the etiologic agent of melioidosis, is a saprophytic bacterium readily isolated from wet soils of countries bordering the equator. Burkholderia mallei is a host-adapted clone of B. pseudomallei that does not persist outside of its equine reservoir and causes the zoonosis glanders, which is endemic in Asia, Africa, the Middle East and South America. Infection by these organisms typically occurs via percutaneous inoculation or inhalation of aerosols, and the most common manifestation is severe pneumonia leading to fatal bacteremia. Glanders and melioidosis are difficult to diagnose and require prolonged antibiotic therapy with low success rates. There are no vaccines available to protect against either Burkholderia species, and there is concern regarding their use as biological warfare agents given that B. mallei has previously been utilized in this manner. Hence, experiments were performed to establish a mouse model of aerosol infection to study the organisms and develop countermeasures. Using a hand-held aerosolizer, BALB/c mice were inoculated intratracheally with strains B. pseudomallei 1026b and B. mallei ATCC23344 and growth of the agents in the lungs, as well as dissemination to the spleen, were examined. Mice infected with 10(2), 10(3) and 10(4) organisms were unable to control growth of B. mallei in the lungs and bacteria rapidly disseminated to the spleen. Though similar results were observed in mice inoculated with 10(3) and 10(4) B. pseudomallei cells, animals infected with 10(2) organisms controlled bacterial replication in the lungs, dissemination to the spleen, and the extent of bacteremia. Analysis of sera from mice surviving acute infection revealed that animals produced antibodies against antigens known to be targets of the immune response in humans. Taken together, these data show that small volume aerosol inoculation of mice results in acute disease, dose-dependent chronic infection, and immune responses that correlate with those seen in human infections. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/24098563/Use_of_a_safe_reproducible_and_rapid_aerosol_delivery_method_to_study_infection_by_Burkholderia_pseudomallei_and_Burkholderia_mallei_in_mice_ L2 - https://dx.plos.org/10.1371/journal.pone.0076804 DB - PRIME DP - Unbound Medicine ER -