Dataset Information

Disulfide bonds are critical for stabilizing cell division, cell envelope biogenesis, and antibiotic resistance proteins in mycobacteria

ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Mycobacterium Smegmatis Str. Mc2 155 (ncbitaxon:246196)

SUBMITTER: Cristina Landeta Amber L. Mosley

PROVIDER: MSV000096877 | MassIVE | Thu Jan 16 16:00:00 GMT 2025

SECONDARY ACCESSION(S): PXD059898

REPOSITORIES: MassIVE

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Disulfide bonds are critical for stabilizing cell division, cell envelope biogenesis, and antibiotic resistance proteins in mycobacteria.

Mejia-Santana Adrian A Collins Rebecca R Doud Emma H EH Landeta Cristina C

mBio 20250731 9

Mycobacteria, including Mycobacterium tuberculosis-the etiological agent of tuberculosis-possess a unique and impermeable cell envelope that is critical for survival and antibiotic resistance. The assembly and maintenance of this envelope depend on properly folded proteins, yet the role of disulfide bond formation in these processes remains poorly understood. Mycobacteria rely on two membrane enzymes, disulfide bond formation protein A (DsbA) and vitamin K</ ...[more]

PMID: 40741763

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