Virulence of the melioidosis pathogen Burkholderia pseudomallei requires the oxidoreductase membrane protein DsbB

R M McMahon; P M Ireland; Derek S Sarovich; G Petit; C H Jenkins; M Sarkar-Tyson; B J Currie; Jennifer L Martin

doi:10.1128/IAI.00938-17

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Virulence of the melioidosis pathogen Burkholderia pseudomallei requires the oxidoreductase membrane protein DsbB

Journal article

Open access

Peer reviewed

Virulence of the melioidosis pathogen Burkholderia pseudomallei requires the oxidoreductase membrane protein DsbB

R M McMahon, P M Ireland, Derek S Sarovich, G Petit, C H Jenkins, M Sarkar-Tyson, B J Currie and Jennifer L Martin

Infection and immunity, Vol.86(5)

2018

DOI: https://doi.org/10.1128/IAI.00938-17

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Abstract

burkholderia pseudomallei

disulfide bond protein

melioidosis

oxidoreductases

virulence determinants

x-ray crystallography

The naturally antibiotic-resistant bacterium Burkholderia pseudomallei is the causative agent of melioidosis, a disease with stubbornly high mortality and a complex, protracted treatment regimen. The worldwide incidence of melioidosis is likely grossly underreported, though it is known to be highly endemic in northern Australia and Southeast Asia. Bacterial disulfide bond (DSB) proteins catalyze the oxidative folding and isomerization of disulfide bonds in substrate proteins. In the present study, we demonstrate that B. pseudomallei membrane protein disulfide bond protein B (BpsDsbB) forms a functional redox relay with the previously characterized virulence mediator B. pseudomallei disulfide bond protein A (BpsDsbA). Genomic analysis of diverse B. pseudomallei clinical isolates demonstrated that dsbB is a highly conserved core gene. Critically, we show that DsbB is required for virulence in B. pseudomallei. A panel of B. pseudomallei dsbB deletion strains (K96243, 576, MSHR2511, MSHR0305b, and MSHR5858) were phenotypically diverse according to the results of in vitro assays that assess hallmarks of virulence. Irrespective of their in vitro virulence phenotypes, two deletion strains were attenuated in a BALB/c mouse model of infection. A crystal structure of a DsbB-derived peptide complexed with BpsDsbA provides the first molecular characterization of their interaction. This work contributes to our broader understanding of DSB redox biology and will support the design of antimicrobial drugs active against this important family of bacterial virulence targets. © 2018 American Society for Microbiology.

Details

Title: Virulence of the melioidosis pathogen Burkholderia pseudomallei requires the oxidoreductase membrane protein DsbB
Authors: R M McMahon (Author) - University of Queensland
P M Ireland (Author) - Defence Science and Technology Laboratory
Derek S Sarovich (Author) - University of the Sunshine Coast - Faculty of Science, Health, Education and Engineering
G Petit (Author) - University of Queensland
C H Jenkins (Author) - Defence Science and Technology Laboratory
M Sarkar-Tyson (Author) - University of Western Australia
B J Currie (Author) - Menzies School of Health Research
Jennifer L Martin (Author) - University of Queensland
Publication details: Infection and immunity, Vol.86(5)
Publisher: American Society for Microbiology
Date published: 2018
DOI: 10.1128/IAI.00938-17
ISSN: 0019-9567
Copyright note: Copyright © 2018 American Society for Microbiology. The author's accepted version is reproduced here in accordance with the publisher's copyright policy. The definitive version is available at http://aem.asm.org/
Organisation Unit: University of the Sunshine Coast, Queensland; Centre for Bioinnovation
Language: English
Record Identifier: 99450992002621
Output Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Web Of Science research areas: Immunology; Infectious Diseases

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