Browsing by Subject "Mycobacteria"

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    Disulfide bonds are required for cell division, cell envelope biogenesis and antibiotic resistance proteins in mycobacteria
    (bioRxiv, 2025-01-28) Mejia-Santana, Adrian; Collins, Rebecca; Doud, Emma H.; Landeta, Cristina; Biochemistry and Molecular Biology, School of Medicine
    Mycobacteria, including Mycobacterium tuberculosis-the etiological agent of tuberculosis-have a unique cell envelope critical for their survival and resistance. The cell envelope's assembly and maintenance influence permeability, making it a key target against multidrug-resistant strains. Disulfide bond (DSB) 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 cysteine profiling 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. Furthermore, chemical inhibition of VKOR results in phenotypes similar to those of Δvkor. Thus, targeting DsbA-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.
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    Iron Supplementation Therapy, A Friend and Foe of Mycobacterial Infections?
    (MDPI, 2019-05-17) Agoro, Rafiou; Mura, Catherine; Medical and Molecular Genetics, School of Medicine
    Iron is an essential element that is required for oxygen transfer, redox, and metabolic activities in mammals and bacteria. Mycobacteria, some of the most prevalent infectious agents in the world, require iron as growth factor. Mycobacterial-infected hosts set up a series of defense mechanisms, including systemic iron restriction and cellular iron distribution, whereas mycobacteria have developed sophisticated strategies to acquire iron from their hosts and to protect themselves from iron's harmful effects. Therefore, it is assumed that host iron and iron-binding proteins, and natural or synthetic chelators would be keys targets to inhibit mycobacterial proliferation and may have a therapeutic potential. Beyond this hypothesis, recent evidence indicates a host protective effect of iron against mycobacterial infections likely through promoting remodeled immune response. In this review, we discuss experimental procedures and clinical observations that highlight the role of the immune response against mycobacteria under various iron availability conditions. In addition, we discuss the clinical relevance of our knowledge regarding host susceptibility to mycobacteria in the context of iron availability and suggest future directions for research on the relationship between host iron and the immune response and the use of iron as a therapeutic agent.