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Title: The proteobacterial species Burkholderia pseudomallei produces ergothioneine, which enhances virulence in mammalian infection
Authors: Gamage, Akshamal M 
Liao, Cangsong
Cheah, Irwin K 
Chen, Yahua 
Lim, Daniel RX 
Ku, Joanne WK 
Chee, Rhonda Sin Ling
Gengenbacher, Martin 
Seebeck, Florian P
Halliwell, Barry 
Gan, Yunn-Hwen 
Keywords: microbial antioxidant
oxidative stress
Burkholderia thailandensis
Issue Date: 1-Dec-2018
Citation: Gamage, Akshamal M, Liao, Cangsong, Cheah, Irwin K, Chen, Yahua, Lim, Daniel RX, Ku, Joanne WK, Chee, Rhonda Sin Ling, Gengenbacher, Martin, Seebeck, Florian P, Halliwell, Barry, Gan, Yunn-Hwen (2018-12-01). The proteobacterial species Burkholderia pseudomallei produces ergothioneine, which enhances virulence in mammalian infection. FASEB JOURNAL 32 (12) : 6395-6409. ScholarBank@NUS Repository.
Abstract: 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 g-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.
ISSN: 0892-6638
DOI: 10.1096/fj.201800716
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