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PXD027688

PXD027688 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleThiol-Based Functional Mimicry of Phosphorylation of the Two-Component System Response Regulator ArcA Promotes Pathogenesis in Enteric Pathogens
DescriptionPathogenic bacteria can rapidly respond to stress environments, such as exposure to reactive oxygen species (ROS). The thiol (-SH) groups of cysteine residues in many proteins serve as redox-sensitive switches, providing triggers for ROS-mediated signaling events. In this study, we profiled the reversible thiol oxidation during ROS exposure of the proteome of Vibrio cholerae, a Gram-negative human pathogen that causes cholera. We identified posttranslational modifications of two cysteine residues of ArcA, a response regulator that is known to be phosphorylated under oxygen limiting conditions and regulates global carbon oxidation pathways. We showed that although ROS exposure abolished ArcA phosphorylation, it induced the formation of an intramolecular disulfide that promoted ArcA-ArcA interaction. Thiol oxidation of ArcA led to sustained ArcA activity and ROS resistance. We further demonstrated that V. cholerae ArcA cysteine residues were oxidized in cholera patient diarrheal stools, and that ArcA thiol oxidation is crucial for V. cholerae in vitro ROS resistance, colonization of ROS-rich gut niches, and environmental survival. Moreover, in other enteric pathogens such as Salmonella enterica, the cysteine residues in ArcA orthologs are conserved and thiol oxidation of ArcA plays important roles in ROS resistance both in vitro and in host cells. These results suggest that in enteric pathogens, as a response to ROS insults, thiol oxidation of ArcA is able to functionally mimic phosphorylation and retain ArcA activity, allowing for a balance in the expression of stress-related and pathogenesis-related genetic programs.
HostingRepositoryMassIVE
AnnounceDate2022-08-24
AnnouncementXMLSubmission_2022-08-24_06:46:15.963.xml
DigitalObjectIdentifier
ReviewLevelNon peer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterHsin-Yao Tang
SpeciesList scientific name: Vibrio cholerae; NCBI TaxID: 666;
ModificationListOxidation; iodoTMT; Nethylmaleimide
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02021-08-02 12:22:42ID requested
12022-08-24 06:46:16announced
Publication List
no publication
Keyword List
submitter keyword: TCSs, phosphorylation, thiol oxidation, disulfide bond, ArcA, Vibrio cholerae, Salmonella, colonization
Contact List
Jun Zhu
contact affiliationDepartment of Microbiology, Perelman School of Medicine, University of Pennsylvania
contact emailjunzhu@pennmedicine.upenn.edu
lab head
Hsin-Yao Tang
contact affiliationThe Wistar Institute
contact emailtangh@wistar.org
dataset submitter
Full Dataset Link List
MassIVE dataset URI
Dataset FTP location
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