MassIVE MSV000087932

Partial Public PXD027688

Thiol-Based Functional Mimicry of Phosphorylation of the Two-Component System Response Regulator ArcA Promotes Pathogenesis in Enteric Pathogens

Subscribe Comment Convert Spectra Add Reanalysis

Description

Pathogenic 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. [doi:10.25345/C5KZ6Q] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: TCSs ; phosphorylation ; thiol oxidation ; disulfide bond ; ArcA ; Vibrio cholerae ; Salmonella ; colonization

Contact

Principal Investigators:
(in alphabetical order) 		Jun Zhu, Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, USA
Submitting User: tangh
Number of Files:
Total Size:
Spectra:
Subscribers:
 
Owner Reanalyses
Experimental Design
    Conditions:
    Biological Replicates:
    Technical Replicates:
 
Identification Results
    Proteins (Human, Remapped):
    Proteins (Reported):
    Peptides:
    Variant Peptides:
    PSMs:
 
Quantification Results
    Differential Proteins:
    Quantified Proteins:
 
Browse Dataset Files
 
FTP Download Link (click to copy):

Species

Instrument

Modifications

- Dataset Reanalyses

+ Dataset History

Click here to queue conversion of this dataset's submitted spectrum files to open formats (e.g. mzML). This process may take some time.

When complete, the converted files will be available in the "ccms_peak" subdirectory of the dataset's FTP space (accessible via the "FTP Download" link to the right).
Number of distinct conditions across all analyses (original submission and reanalyses) associated with this dataset.

Distinct condition labels are counted across all files submitted in the "Metadata" category having a "Condition" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct biological replicates across all analyses (original submission and reanalyses) associated with this dataset.

Distinct replicate labels are counted across all files submitted in the "Metadata" category having a "BioReplicate" or "Replicate" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct technical replicates across all analyses (original submission and reanalyses) associated with this dataset.

The technical replicate count is defined as the maximum number of times any one distinct combination of condition and biological replicate was analyzed across all files submitted in the "Metadata" category. In the case of fractionated experiments, only the first fraction is considered.

"N/A" means no results of this type were submitted.
Originally identified proteins that were automatically remapped by MassIVE to proteins in the SwissProt human reference database.

"N/A" means no results of this type were submitted.
Number of distinct protein accessions reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Number of distinct unmodified peptide sequences reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Number of distinct peptide sequences (including modified variants or peptidoforms) reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Total number of peptide-spectrum matches (i.e. spectrum identifications) reported across all analyses (original submission and reanalyses) associated with this dataset.

"N/A" means no results of this type were submitted.
Number of distinct proteins quantified across all analyses (original submission and reanalyses) associated with this dataset.

Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

"N/A" means no results of this type were submitted.
Number of distinct proteins found to be differentially abundant in at least one comparison across all analyses (original submission and reanalyses) associated with this dataset.

A protein is differentially abundant if its change in abundance across conditions is found to be statistically significant with an adjusted p-value <= 0.05 and lists no issues associated with statistical tests for differential abundance.

Distinct protein accessions are counted across all files submitted in the "Statistical Analysis of Quantified Analytes" category having a "Protein" column in this dataset.

"N/A" means no results of this type were submitted.
This dataset may not contain all raw spectra data as originally deposited in PRIDE. It has been imported to MassIVE for reanalysis purposes, so its spectra data here may consist solely of processed peak lists suitable for reanalysis with most software.