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PXD036679-1

PXD036679 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMacrophage infectivity potentiator protein, a peptidyl prolyl cis/trans isomerase, essential for Coxiella burnetii growth and pathogenesis
DescriptionCoxiella burnetii is a Gram-negative intracellular pathogen that causes the debilitating disease Q fever, which affects both animals and humans. The only available vaccine, Q-Vax, is effective but has a high risk of severe adverse reactions, limiting its use as a countermeasure to contain outbreaks. Therefore, it is essential to identify new drug targets to treat this infection. Macrophage infectivity potentiator (Mip) proteins catalyze the folding of proline-containing proteins through their peptidyl prolyl cis-trans isomerase (PPIase) activity and have been shown to play an important role in the virulence of several pathogenic bacteria but to date its role in C. burnetii pathogenesis has not been investigated. This study demonstrates that CbMip is likely to be an essential protein in C. burnetii. Pipecolic acid derived compounds, SF235 and AN296 demonstrate inhibitory activities against CbMip and these compounds were found to significantly inhibit intracellular replication of C. burnetii in both HeLa and THP-1 cells. Furthermore, SF235 and AN296 were also found to exhibit antibiotic properties against both the virulent (Phase I) and avirulent (Phase II) forms of C. burnetii Nine Mile Strain RSA439 in axenic culture with comparative proteomic demonstrating selective alterations in response to these agents. This study also showed that exposure of C. burnetii to Mip inhibitors resulted in increased sensitivity to oxidative stress. Furthermore, compounds SF235 and AN296 demonstrated protective activity in vivo and significantly improved the survival of Galleria mellonella infected with C. burnetii. These results suggest that unlike in other bacteria, Mip in C. burnetii is required for growth and replication and that inhibitors against CbMip offer potential as novel therapeutics against C. burnetii.
HostingRepositoryPRIDE
AnnounceDate2023-06-15
AnnouncementXMLSubmission_2023-06-15_00:12:10.767.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterNichollasScott
SpeciesList scientific name: Coxiella burnetii Dugway 5J108-111; NCBI TaxID: 434922;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-09-12 06:46:36ID requested
12023-06-15 00:12:11announced
22024-10-22 05:48:16announced2024-10-22: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: proteomics,Coxiella, peptidyl prolyl cis/trans isomerase
Contact List
MitaliSarkar-Tyson
contact affiliationMarshall Centre for Infectious Disease Research and Training, School of Biomedical Sciences, The University of Western Australia, Nedlands, Western Australia, 6009, Australia
contact emailmitali.sarkar-tyson@uwa.edu.au
lab head
NichollasScott
contact affiliationUniversity of Melbourne
contact emailnichollas.scott@unimelb.edu.au
dataset submitter
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Dataset FTP location
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