Putative ATP-Binding Cassette Transporter Is Essential for Brucella ovis Pathogenesis in Mice

Abstract

ABSTRACT Brucella ovis is a major cause of reproductive failure in sheep, which is associated with epididymitis and infertility in rams. Importantly, B. ovis is one of the few Brucella species that is not zoonotic. Due to the scarcity of studies on B. ovis infection, a murine model of infection was developed. The roles of B. ovis genes encoding a putative hemagglutinin and an ABC transporter were investigated in the mouse model. The kinetics of B. ovis infection were similar in BALB/c and C57BL/6 mice, and both strains of mice developed multifocal microgranulomas in the liver and spleen, but only minimal colonization and histopathological changes were observed in the genital tract. Therefore, the mouse was considered a suitable infection model for B. ovis but not for B. ovis -induced genital disease. Two mutant strains were generated in this study (the Δ abcAB and Δ hmg strains). The B. ovis Δ abcAB strain was attenuated in the spleens and livers of BALB/c mice compared to the wild-type (WT) strain ( P < 0.001). Conversely, the Δ hmg strain infected mice at the same level as WT B. ovis , suggesting that a putative hemagglutinin is not required for B. ovis pathogenesis. Additionally, the Δ abcAB strain did not survive in peritoneal macrophages, extracellularly in the peritoneal cavity, or in RAW 264.7 macrophages. Moreover, infection with the Δ abcAB strain was not lethal for male regulatory factor 1-knockout mice, whereas infection with the B. ovis WT strain was 100% lethal within 14 days postinfection. These results confirm that the predicted ABC transporter is required for the full virulence and survival of B. ovis in vivo .