title: Characterization of betaine aldehyde dehydrogenase (BetB) as an essential virulence factor of Brucella abortus.
abstract: The pathogenic mechanisms of Brucellosis used to adapt to the harsh intracellular environment of the host cell are not fully understood. The present study investigated the in vitro and in vivo characteristics of B. abortus betaine aldehyde dehydrogenase (BetB) (Gene Bank ID: 006932) using a betB deletion mutant constructed from virulent B. abortus 544. In test under stress conditions, including osmotic- and acid stress-resistance, the betB mutant had a lower osmotic-resistance than B. abortus wild-type. In addition, the betB mutant showed higher internalization rates compared to the wild-type strain; however, it also displayed replication failures in HeLa cells and RAW 264.7 macrophages. During internalization, compared to the wild-type strain, the betB mutant was more adherent to the host surface and showed enhanced phosphorylation of protein kinases, two processes that promote phagocytic activity, in host cells. During intracellular trafficking, colocalization of B. abortus-containing phagosomes with LAMP-1 was elevated in betB mutant-infected cells compared to the wild-type cells. In mice, the betB mutant was predominantly cleared from spleens compared to the wild-type strain after 2 weeks post-infection, and the vaccination test with the live betB mutant showed effective protection against challenge infection with the virulent wild-type strain. These findings suggested that the B. abortus betB gene substantially affects the phagocytic pathway in human phagocytes and in host cells in mice. Furthermore, this study highlights the potential use of the B. abortus betB mutant as a live vaccine for the control of brucellosis.
authors.affiliation: Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Republic of Korea; Animal and Plant Quarantine Agency, Anyang, Gyeonggi-do 430-757, Republic of Korea.
authors.forename: Jin Ju
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Jae Hong
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Dae Geun
authors.initials: DG
authors.lastname: Kim
authors.affiliation: Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Dong Hyeok
authors.initials: DH
authors.lastname: Kim
authors.affiliation: Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Hannah Leah
authors.initials: HL
authors.lastname: Simborio
authors.affiliation: Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Won Gi
authors.initials: WG
authors.lastname: Min
authors.affiliation: Department of Veterinary Physiology, College of Veterinary Medicine, Kyungpook National University, Daegu 702-701, Republic of Korea.
authors.forename: Man Hee
authors.initials: MH
authors.lastname: Rhee
authors.affiliation: Center for Nutraceutical and Pharmaceutical Materials, Myongji University, Yongin 449-728, Republic of Korea.
authors.forename: Jong Hwan
authors.initials: JH
authors.lastname: Lim
authors.affiliation: Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 660-701, Republic of Korea.
authors.forename: Hong Hee
authors.initials: HH
authors.lastname: Chang
authors.affiliation: Institute of Animal Medicine, College of Veterinary Medicine, Gyeongsang National University, Jinju 660-701, Republic of Korea; Institute of Agriculture and Life Science, Gyeongsang National University, Jinju 660-701, Republic of Korea. Electronic address: kimsuk@gnu.ac.kr.
authors.forename: Suk
authors.initials: S
authors.lastname: Kim
mesh_terms: D000818:Animals; D001422:Bacterial Adhesion / Q000235:genetics; D001428:Bacterial Vaccines; D050728:Betaine-Aldehyde Dehydrogenase / Q000235:genetics* / Q000378:metabolism*; D002003:Brucella abortus / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D002006:Brucellosis / Q000276:immunology / Q000382:microbiology* / Q000517:prevention & control; D006367:HeLa Cells; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009997:Osmotic Pressure; D010586:Phagocytes / Q000382:microbiology; D017384:Sequence Deletion; D013154:Spleen / Q000382:microbiology; D037521:Virulence Factors / Q000235:genetics*
chemical_list: D001428:Bacterial Vaccines; D037521:Virulence Factors; D050728:Betaine-Aldehyde Dehydrogenase
keywords: B. abortus; Phagocyte; Phagocytic pathway; Virulence; betB