Mycobacterium, including Mycobacterium tuberculosis, the etiological agent of tuberculosis, have a unique cell envelope critical for their survival and antibacterial resistance. The cell envelope's assembly and maintenance influence permeability, making it a key target against multidrug resistant strains. Disulfide bond (SB) formation is crucial for the folding of cell envelope proteins The DSB pathway in mycobacteria includes two enzymes, DsbA and VKOR, required for survival. Using bioinformatics and cystine prfiling proteomics, we identified cell envelope proteins dependent on DSBs. We validated via in vivo alkylation, that key proteins like LamA (MmpS3, PstP, LpqW, and EmbB rely on DSBs for stability. Their stability is disrupted in the Delta VKOR mutant or by VKOR inhibition. Thus targeting DsbA and VKOR systems could compromise both cell division and mycomembrane integrity. These findings emphasize the potential of DSB inhibition as a novel strategy to combat mycobacterial infections.
[doi:10.25345/C5P26QG14]
[dataset license: CC0 1.0 Universal (CC0 1.0)]
Keywords: disulfide bonds ; oxidative protein folding ; DsbA ; VKOR ; essential proteins ; PstP ; mycobacteria ; actinobacteria ; mycomembrane ; PP2C ; EmbB ; Rv2507 ; MmpS3 ; cysteine-profiling mass spectrometry ; DatasetType:Proteomics
|
Principal Investigators: (in alphabetical order) |
Amber L. Mosley, Indiana University School of Medicine, USA Cristina Landeta, Indiana University, USA |
| Submitting User: | edoud |
Mejia-Santana A, Collins R, Doud EH, Landeta C.
Disulfide bonds are critical for stabilizing cell division, cell envelope biogenesis, and antibiotic resistance proteins in mycobacteria.
mBio. 2025 Sep 10;16(9):e0108325. Epub 2025 Jul 31.
| 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 | Browse Results |
|
FTP Download Link (click to copy):
|
|