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Infect Immun. 2018 Oct 29. pii: IAI.00255-18. doi: 10.1128/IAI.00255-18. [Epub ahead of print]

Brucella neotomae recapitulates attributes of zoonotic human disease in a murine infection model.

Author information

1
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215.
2
Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215 jekirby@bidmc.harvard.edu.

Abstract

Brucella are Gram-negative pathogens that cause chronic systemic infection in farm animals and zoonotic infection in humans. Study of the Brucella genus has been hindered by the need for biosafety level three, select agent containment. Brucella neotomae, originally isolated from the desert pack rat, presented an opportunity to develop an alternative, non-select agent experimental model. Our prior in vitro work indicated that the cell biology and type IV secretion system (T4SS) dependence of B. neotomae intracellular replication was similar to observations for human pathogenic, select agent Brucella species. Therefore, here we investigated the pathobiology of B. neotomae infection in the BALB/c mouse. During a sustained infectious course, Brucella neotomae replicated and persisted in reticuloendothelial organs. Bioluminescent imaging; histopathological and PCR-based analysis demonstrated that the T4SS contributed to efficient early infection of the liver, spleen and lymph nodes; granuloma formation and hepatosplenomegaly; and; early induction of Th-1 associated cytokine gene expression. Infectious course and pathologies in the murine model showed similarity to prior observations of primate and native host infection with zoonotic Brucella species. Therefore, the B. neotomae BALB/c infection model offers a promising system to accelerate and complement experimental work in the Brucella genus.

PMID:
30373892
DOI:
10.1128/IAI.00255-18

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