Journal article
Peptidyl-Prolyl Isomerase ppiB Is Essential for Proteome Homeostasis and Virulence in Burkholderia pseudomallei
Infection and immunity, Vol.87(10), e00528-19
2019
Abstract
Burkholderia pseudomallei is the causative agent of melioidosis, a disease endemic in South-East Asia and northern Australia. Mortality rates in these areas are high even with antimicrobial treatment, and there are few options for effective therapy. Therefore there is a requirement to identify anti-bacterial targets for the development of novel treatments. Cyclophilins are a family of highly conserved enzymes important in multiple cellular processes. Cyclophilins catalyse the cis-trans isomerization of xaa-proline bonds, a rate limiting step in protein folding which has been shown to be important for bacterial virulence. B. pseudomallei encodes a putative cyclophilin B gene, ppiB, the role of which was investigated. A mutant strain, BpsΔppiB, demonstrates impaired biofilm formation and reduced motility. Macrophage invasion and survival assays showed that although BpsΔppiB retained the ability to infect macrophages, it had reduced survival and lacked the ability to spread cell-to-cell, indicating ppiB is essential for B. pseudomallei virulence. This is reflected in the BALB/c mouse infection model demonstrating the requirement of ppiB for in vivo disease dissemination and progression. Proteomic analysis demonstrates that the loss of PpiB leads to pleiotropic effects supporting the role of PpiB in maintaining proteome homeostasis. The loss of PpiB leads to decreased abundance of multiple virulence determinants including flagellar machinery and alterations in Type VI secretion system proteins. In addition, the loss of ppiB leads to increased sensitivity towards multiple antibiotics including meropenem and doxycycline, highlighting ppiB inhibition as a promising anti-virulence target to both treat B. pseudomallei infections and increase antibiotic efficacy.
Details
- Title
- Peptidyl-Prolyl Isomerase ppiB Is Essential for Proteome Homeostasis and Virulence in Burkholderia pseudomallei
- Authors
- N M Bzdyl (Author) - University of Western AustraliaN E Scott (Author) - University of MelbourneI H Norville (Author) - Defence Science Technology Laboratory (Dstl), United KingdomA E Scott (Author) - Defence Science Technology Laboratory (Dstl), United KingdomT Atkins (Author) - Defence Science Technology Laboratory (Dstl), United KingdomS Pang (Author) - Murdoch UniversityDerek S Sarovich (Author) - University of the Sunshine CoastG Coombs (Author) - Murdoch UniversityT J J Inglis (Author) - University of Western AustraliaC M Kahler (Author) - University of Western AustraliaM Sarkar-Tyson (Author) - University of Western Australia
- Publication details
- Infection and immunity, Vol.87(10), e00528-19
- Publisher
- American Society for Microbiology
- Date published
- 2019
- DOI
- 10.1128/IAI.00528-19
- ISSN
- 0019-9567
- Copyright note
- Copyright © 2019 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
- 99450768202621
- Output Type
- Journal article
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