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Characterization of Brucella canis infection in mice.

ABSTRACT: Canine brucellosis, caused by Brucella canis, is a disease of dogs and represents a public health concern as it can be transmitted to humans. Canine brucellosis is on the rise in the United States and there is currently no vaccine for use in dogs. Mice have been extensively utilized to investigate host-pathogen interactions and vaccine candidates for smooth Brucella species and could serve a similar role for studying B. canis. However, comparatively little is known about B. canis infection in mice. The objective of this study was to characterize the kinetics of colonization and pathogenicity of B. canis in mice in order to evaluate the mouse as a model for studying this pathogen. C57BL/6 mice were inoculated intraperitoneally with 105, 107, or 109 CFU of Brucella canis RM6/66 and euthanized 1-, 2-, 4-, 6-, 9-, and 12-weeks post-inoculation. B. canis induced splenomegaly in mice infected with 109 CFU at 1- and 2 weeks post-inoculation while no gross lesions were observed in other dose groups. Infection at the two higher doses resulted in dose-dependent granulomatous hepatitis and histiocytic infiltration of the spleen and mesenteric lymph nodes by 1-2 weeks. B. canis was cultured from the liver, spleen, uterus, bone marrow, lung, and kidney in all groups with colonization declining at a slow but steady rate throughout the experiment. Clearance was achieved by 9 weeks 105 CFU group and by 12 weeks in the 107 CFU group, while B. canis persisted in the spleen until 12 weeks in the highest dose group. Although B. canis does not demonstrate significant replication in C57BL/6 mice, it has the ability to establish an infection, induce splenomegaly, and persist for several weeks in multiple organs. Moreover, 1 x 107 CFU appears to be a suitable challenge dose for investigating vaccine safety.

SUBMITTER: Stranahan LW

PROVIDER: S-EPMC6586350 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Characterization of Brucella canis infection in mice.

Stranahan Lauren W LW Khalaf Omar H OH Garcia-Gonzalez Daniel G DG Arenas-Gamboa Angela M AM

PloS one 20190620 6

Canine brucellosis, caused by Brucella canis, is a disease of dogs and represents a public health concern as it can be transmitted to humans. Canine brucellosis is on the rise in the United States and there is currently no vaccine for use in dogs. Mice have been extensively utilized to investigate host-pathogen interactions and vaccine candidates for smooth Brucella species and could serve a similar role for studying B. canis. However, comparatively little is known about B. canis infection in mi ...[more]

PMID: 31220185

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Project description:Brucella canis is a Gram-negative, facultative intracellular bacterium and the causative agent of canine brucellosis, a highly contagious disease of dogs that can be transmitted to humans. Unfortunately, no vaccine is available to prevent infection. We recently characterized the kinetics of B. canis infection in the mouse model, establishing the required dose necessary to achieve systemic infection. The objective of this study was to investigate the utility of the mouse model in assessing canine brucellosis vaccine candidates and to subsequently investigate the safety and efficacy of a live attenuated vaccine, the B. canis RM6/66 ?vjbR strain. Mice vaccinated with a dose of 109 CFU of the vaccine strain by both intraperitoneal and subcutaneous routes were afforded significant protection against organ colonization and development of histopathologic lesions following intraperitoneal challenge. Addition of an adjuvant or a booster dose 2 weeks following initial vaccination did not alter protection levels. Vaccination also resulted in a robust humoral immune response in mice, and B. canis RM6/66 ?vjbR was capable of activating canine dendritic cells in vitro These data demonstrate that the B. canis RM6/66 ?vjbR strain shows promise as a vaccine for canine brucellosis and validates the mouse model for future vaccine efficacy studies.IMPORTANCE Canine brucellosis, caused by Brucella canis, is the primary cause of reproductive failure in dogs and represents a public health concern due to its zoonotic nature. Cases in dogs in the United States have been increasing due to the persistent nature of the bacterium, deficiencies in current diagnostic testing, and, most importantly, the lack of a protective vaccine. Current estimates place the seroprevalence of B. canis in the southern United States at 7% to 8%, but with the unprecedented rates of animals moving across state and international borders and the lack of federal regulations in regard to testing, the true seroprevalence of B. canis in the United States may very well be higher. Vaccination represents the most effective method of brucellosis control and, in response to the demand for a vaccine against B. canis, we have developed the live attenuated B. canis RM6/66 ?vjbR vaccine strain capable of protecting mice against challenge.

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Characterization of Brucella canis infection in mice.

Publications

Characterization of Brucella canis infection in mice.

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