期刊
FASEB JOURNAL
卷 32, 期 12, 页码 6395-6409出版社
FEDERATION AMER SOC EXP BIOL
DOI: 10.1096/fj.201800716
关键词
microbial antioxidant; oxidative stress; glutathione; Burkholderia thailandensis
资金
- National Medical Research Council Center, Singapore Ministry of Health Grant MINE Core [4 BSL-3 NMRC/CG/013/2013]
- National University of Singapore Yong Loo Lin School of Medicine BSL-3 Core Facility
- Sino-Swiss Science and Technology Cooperation
- Professur fur Molekulare Bionik
- European Research Council [ERC-2013-StG 336559]
- Tan Chin Tuan Foundation
- China Scholarship Council
Bacteria use various endogenous antioxidants for protection against oxidative stress associated with environmental survival or host infection. Although glutathione (GSH) is the most abundant and widely used antioxidant in Proteobacteria, ergothioneine (EGT) is another microbial antioxidant, mainly produced by fungi and Actinobacteria. The Burkholderia genus is found in diverse environmental niches. We observed that gene homologs required for the synthesis of EGT are widely distributed throughout the genus. By generating gene-deletion mutants and monitoring production with isotope-labeled substrates, we show that pathogenic Burkholderia pseudomallei and environmental B. thailandensis are able to synthesize EGT de novo. Unlike most other bacterial EGT synthesis pathways described, Burkholderia spp. use cysteine rather than -glutamyl cysteine as the thiol donor. Analysis of recombinant EgtB indicated that it is a proficient sulfoxide synthase, despite divergence in the active site architecture from that of mycobacteria. The absence of GSH, but not EGT, increased bacterial susceptibility to oxidative stresses in vitro. However, deletion of EGT synthesis conferred a reduced fitness to B. pseudomallei, with a delay in organ colonization and time to death during mouse infection. Therefore, despite the lack of an apparent antioxidant role in vitro, EGT is important for optimal bacterial pathogenesis in the mammalian host.Gamage, A. M., Liao, C., Cheah, I. K., Chen, Y., Lim, D. R. X., Ku, J. W. K., Chee, R. S. L., Gengenbacher, M., Seebeck, F. P., Halliwell, B., Gan, Y.-H. The proteobacterial species Burkholderia pseudomallei produces ergothioneine, which enhances virulence in mammalian infection.
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