title: Brucella abortus mutants lacking ATP-binding cassette transporter proteins are highly attenuated in virulence and confer protective immunity against virulent B. abortus challenge in BALB/c mice.
abstract: Brucella abortus RB51 is an attenuated vaccine strain that has been most frequently used for bovine brucellosis. Although it is known to provide good protection in cattle, it still has some drawbacks including resistance to rifampicin, residual virulence and pathogenicity in humans. Thus, there has been a continuous interest on new safe and effective bovine vaccine candidates. In the present study, we have constructed unmarked mutants by deleting singly cydD and cydC genes, which encode ATP-binding cassette transporter proteins, from the chromosome of the virulent Brucella abortus isolate from Korean cow (referred to as IVK15). Both IVK15ΔcydD and ΔcydC mutants showed increased sensitivity to metal ions, hydrogen peroxide and acidic pH, which are mimic to intracellular environment during host infection. Additionally, the mutants exhibited a significant growth defect in RAW264.7 cells and greatly attenuated in mice. Vaccination of mice with either IVK15ΔcydC or IVK15ΔcydD mutant could elicit an anti-Brucella specific immunoglobulin G (IgG) and IgG subclass responses as well as enhance the secretion of interferon-gamma, and provided better protection against challenge with B. abortus strain 2308 than with the commercial B. abortus strain RB51 vaccine. Collectively, these results suggest that both IVK15ΔcydC and IVK15ΔcydD mutants could be an attenuated vaccine candidate against B. abortus.
authors.affiliation: College of Veterinary Medicine, Kangwon National University, Chuncheon 200-701, Gangwon-do, South Korea.
authors.forename: Quang Lam
authors.initials: QL
authors.lastname: Truong
authors.affiliation: College of Veterinary Medicine, Kangwon National University, Chuncheon 200-701, Gangwon-do, South Korea.
authors.forename: Youngjae
authors.initials: Y
authors.lastname: Cho
authors.affiliation: College of Veterinary Medicine, Kangwon National University, Chuncheon 200-701, Gangwon-do, South Korea.
authors.forename: Soyeon
authors.initials: S
authors.lastname: Park
authors.affiliation: College of Veterinary Medicine, Kangwon National University, Chuncheon 200-701, Gangwon-do, South Korea.
authors.forename: Bo-Kyoung
authors.initials: BK
authors.lastname: Park
authors.affiliation: College of Veterinary Medicine, Kangwon National University, Chuncheon 200-701, Gangwon-do, South Korea. Electronic address: twhahn@kangwon.ac.kr.
authors.forename: Tae-Wook
authors.initials: TW
authors.lastname: Hahn
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000172:deficiency*; D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D058491:Bacterial Load; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D002003:Brucella abortus / Q000235:genetics / Q000276:immunology* / Q000302:isolation & purification / Q000472:pathogenicity*; D002007:Brucellosis, Bovine / Q000276:immunology / Q000517:prevention & control*; D002417:Cattle; D004195:Disease Models, Animal; D017353:Gene Deletion; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D000067996:RAW 264.7 Cells; D013154:Spleen / Q000382:microbiology / Q000473:pathology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014774:Virulence; D037521:Virulence Factors / Q000172:deficiency*
chemical_list: D018528:ATP-Binding Cassette Transporters; D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D007074:Immunoglobulin G; D014613:Vaccines, Attenuated; D037521:Virulence Factors; D007371:Interferon-gamma
keywords: Attenuation; Brucella abortus; Immune response; Protection; cydDC