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Unlabelled: Phagosomal lysis is a key aspect of mycobacterial infection of host macrophages. Acetylation is a protein modification mediated enzymatically by N-acetyltransferases (NATs) that impacts bacterial pathogenesis and physiology. To identify NATs required for lytic activity, we leveraged a nontubercular pathogen and an established model for hemolysis is a proxy for phagolytic activity.
View Article and Find Full Text PDFLanosterol elevates cytoprotective response through induced-proteasomal degradation of aberrant proteins.
Biochim Biophys Acta Mol Cell Res
February 2024
Cellular and Molecular Neurobiology Unit, Indian Institute of Technology Jodhpur, Rajasthan 342037, India. Electronic address:
Efficient protein synthesis is a basic requirement of our cells to replace the old or defective proteins from the intrinsic crowded biomolecular environment. The interconnection among synthesis, folding, and degradation of proteins represents central paradigm to proteostasis. Failure of protein quality control (PQC) mechanisms results in the disturbance and inadequate functions of proteome.
View Article and Find Full Text PDFProximity-dependent biotin identification links cholesterol catabolism with branched-chain amino acid degradation in Mycobacterium smegmatis.
FASEB J
July 2023
Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019 - UMR 9017 - CIIL - Center for Infection and Immunity of Lille, F-59000, Lille, France.
Cholesterol is a crucial component in Mycobacterium tuberculosis virulence as it is required for phagocytosis of mycobacteria by macrophages. In addition, the tubercle bacilli can grow using cholesterol as the sole carbon source. Thus, cholesterol catabolism represents a valuable target for the development of new antitubercular drugs.
View Article and Find Full Text PDFSequence and Structural Motifs Controlling the Broad Substrate Specificity of the Mycobacterial Hormone-Sensitive Lipase LipN.
ACS Omega
April 2023
Department of Chemistry and Biochemistry, Butler University, Indianapolis, Indiana 46208, United States.
has a complex life cycle transitioning between active and dormant growth states depending on environmental conditions. LipN (Rv2970c) is a conserved mycobacterial serine hydrolase with regulated catalytic activity at the interface between active and dormant growth conditions. LipN also catalyzes the xenobiotic degradation of a tertiary ester substrate and contains multiple conserved motifs connected with the ability to catalyze the hydrolysis of difficult tertiary ester substrates.
View Article and Find Full Text PDFBolaamphiphile Analogues of 12-bis-THA Cl Are Potent Antimicrobial Therapeutics with Distinct Mechanisms of Action against Bacterial, Mycobacterial, and Fungal Pathogens.
mSphere
February 2023
Institute of Pharmaceutical Science, School of Cancer & Pharmaceutical Sciences, King's College London, London, United Kingdom.
12-Bis-THA Cl [12,12'-(dodecane-1,12-diyl)-bis-(9-amino-1,2,3,4-tetrahydroacridinium) chloride] is a cationic bolalipid adapted from dequalinium chloride (DQC), a bactericidal anti-infective indicated for bacterial vaginosis (BV). Here, we used a structure-activity-relationship study to show that the factors that determine effective killing of bacterial, fungal, and mycobacterial pathogens differ, to generate new analogues with a broader spectrum of activity, and to identify synergistic relationships, most notably with aminoglycosides against Acinetobacter baumannii and Pseudomonas aeruginosa, where the bactericidal killing rate was substantially increased. Like DQC, 12-bis-THA Cl and its analogues accumulate within bacteria and fungi.
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