title: Putative ATP-binding cassette transporter is essential for Brucella ovis pathogenesis in mice.
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 ΔabcAB and Δhmg strains). The B. ovis ΔabcAB strain was attenuated in the spleens and livers of BALB/c mice compared to the wild-type (WT) strain (P < 0.001). Conversely, the Δhmg 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 ΔabcAB strain did not survive in peritoneal macrophages, extracellularly in the peritoneal cavity, or in RAW 264.7 macrophages. Moreover, infection with the ΔabcAB 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.
authors.affiliation: Departamento de Clínica e Cirurgia Veterinária, Escola de Veterinária, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.
authors.forename: Teane M A
authors.initials: TM
authors.lastname: Silva
authors.forename: Tatiane A
authors.initials: TA
authors.lastname: Paixão
authors.forename: Erica A
authors.initials: EA
authors.lastname: Costa
authors.forename: Mariana N
authors.initials: MN
authors.lastname: Xavier
authors.forename: Joicy Cortez
authors.initials: JC
authors.lastname: Sá
authors.forename: Valéria S
authors.initials: VS
authors.lastname: Moustacas
authors.forename: Andreas B
authors.initials: AB
authors.lastname: den Hartigh
authors.forename: Alcina V
authors.initials: AV
authors.lastname: Carvalho Neta
authors.forename: Sérgio C
authors.initials: SC
authors.lastname: Oliveira
authors.forename: Renée
authors.initials: R
authors.lastname: Tsolis
authors.forename: Renato L
authors.initials: RL
authors.lastname: Santos
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D042061:Brucella ovis / Q000235:genetics* / Q000472:pathogenicity*; D002006:Brucellosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020133:Reverse Transcriptase Polymerase Chain Reaction; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D001426:Bacterial Proteins; D037521:Virulence Factors