title: Characterization of pathogenesis of and immune response to Burkholderia pseudomallei K96243 using both inhalational and intraperitoneal infection models in BALB/c and C57BL/6 mice.
abstract: Burkholderia pseudomallei, the etiologic agent of melioidosis, is a Gram negative bacterium designated as a Tier 1 threat. This bacterium is known to be endemic in Southeast Asia and Northern Australia and can infect humans and animals by several routes. Inhalational melioidosis has been associated with monsoonal rains in endemic areas and is also a significant concern in the biodefense community. There are currently no effective vaccines for B. pseudomallei and antibiotic treatment can be hampered by non-specific symptomology and also the high rate of naturally occurring antibiotic resistant strains. Well-characterized animal models will be essential when selecting novel medical countermeasures for evaluation prior to human clinical trials. Here, we further characterize differences between the responses of BALB/c and C57BL/6 mice when challenged with low doses of a low-passage and well-defined stock of B. pseudomallei K96243 via either intraperitoneal or aerosol routes of exposure. Before challenge, mice were implanted with a transponder to collect body temperature readings, and daily body weights were also recorded. Mice were euthanized on select days for pathological analyses and determination of the bacterial burden in selected tissues (blood, lungs, liver, and spleen). Additionally, spleen homogenate and sera samples were analyzed to better characterize the host immune response after infection with aerosolized bacteria. These clinical, pathological, and immunological data highlighted and confirmed important similarities and differences between these murine models and exposure routes.
authors.affiliation: Pathology Division, United States Army Medical Research Institute of Infectious Diseases (USAMRIID), Fort Detrick, Frederick, MD, United States of America.
authors.forename: Jeremy J
authors.initials: JJ
authors.lastname: Bearss
authors.affiliation: Bacteriology Division, USAMRIID, Fort Detrick, Frederick, MD, United States of America.
authors.forename: Melissa
authors.initials: M
authors.lastname: Hunter
authors.affiliation: Bacteriology Division, USAMRIID, Fort Detrick, Frederick, MD, United States of America.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Dankmeyer
authors.affiliation: Bacteriology Division, USAMRIID, Fort Detrick, Frederick, MD, United States of America.
authors.forename: Kristen A
authors.initials: KA
authors.lastname: Fritts
authors.affiliation: Bacteriology Division, USAMRIID, Fort Detrick, Frederick, MD, United States of America.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Klimko
authors.affiliation: Bacteriology Division, USAMRIID, Fort Detrick, Frederick, MD, United States of America.
authors.forename: Chris H
authors.initials: CH
authors.lastname: Weaver
authors.affiliation: Bacteriology Division, USAMRIID, Fort Detrick, Frederick, MD, United States of America.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Shoe
authors.affiliation: Bacteriology Division, USAMRIID, Fort Detrick, Frederick, MD, United States of America.
authors.forename: Avery V
authors.initials: AV
authors.lastname: Quirk
authors.affiliation: Bacteriology Division, USAMRIID, Fort Detrick, Frederick, MD, United States of America.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Toothman
authors.affiliation: Bacteriology Division, USAMRIID, Fort Detrick, Frederick, MD, United States of America.
authors.forename: Wendy M
authors.initials: WM
authors.lastname: Webster
authors.affiliation: BioStatisitics Division, USAMRIID, Fort Detrick, Frederick, MD, United States of America.
authors.forename: David P
authors.initials: DP
authors.lastname: Fetterer
authors.affiliation: Bacteriology Division, USAMRIID, Fort Detrick, Frederick, MD, United States of America.
authors.forename: Joel A
authors.initials: JA
authors.lastname: Bozue
authors.affiliation: Bacteriology Division, USAMRIID, Fort Detrick, Frederick, MD, United States of America.
authors.forename: Patricia L
authors.initials: PL
authors.lastname: Worsham
authors.affiliation: Bacteriology Division, USAMRIID, Fort Detrick, Frederick, MD, United States of America.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Welkos
authors.affiliation: Bacteriology Division, USAMRIID, Fort Detrick, Frederick, MD, United States of America.
authors.forename: Kei
authors.initials: K
authors.lastname: Amemiya
authors.affiliation: Bacteriology Division, USAMRIID, Fort Detrick, Frederick, MD, United States of America.
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Cote
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D058491:Bacterial Load; D001831:Body Temperature; D001835:Body Weight; D016957:Burkholderia pseudomallei / Q000254:growth & development / Q000276:immunology* / Q000472:pathogenicity; D015169:Colony Count, Microbial; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006098:Granulocytes / Q000276:immunology / Q000382:microbiology; D006801:Humans; D007113:Immunity, Innate; D007274:Injections, Intraperitoneal; D008099:Liver / Q000276:immunology* / Q000382:microbiology; D008168:Lung / Q000276:immunology* / Q000382:microbiology; D016131:Lymphocyte Subsets / Q000145:classification / Q000276:immunology / Q000382:microbiology; D008554:Melioidosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology / Q000382:microbiology; D013045:Species Specificity; D013154:Spleen / Q000276:immunology* / Q000382:microbiology
chemical_list: D016207:Cytokines