PXD036679-2

PXD036679 is an original dataset announced via ProteomeXchange.

Title	Macrophage infectivity potentiator protein, a peptidyl prolyl cis/trans isomerase, essential for Coxiella burnetii growth and pathogenesis
Description	Coxiella 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.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:48:16.057.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Nichollas Scott
SpeciesList	scientific name: Coxiella burnetii Dugway 5J108-111; NCBI TaxID: 434922;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-12 06:46:36	ID requested
1	2023-06-15 00:12:11	announced
⏵ 2	2024-10-22 05:48:16	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: proteomics,Coxiella, peptidyl prolyl cis/trans isomerase

Mitali Sarkar-Tyson
contact affiliation	Marshall Centre for Infectious Disease Research and Training, School of Biomedical Sciences, The University of Western Australia, Nedlands, Western Australia, 6009, Australia
contact email	mitali.sarkar-tyson@uwa.edu.au
lab head
Nichollas Scott
contact affiliation	University of Melbourne
contact email	nichollas.scott@unimelb.edu.au
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/06/PXD036679

PRIDE project URI

• PRIDE
  1. PXD036679
     1. Label: PRIDE project
     2. Name: Macrophage infectivity potentiator protein, a peptidyl prolyl cis/trans isomerase, essential for Coxiella burnetii growth and pathogenesis