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In vitro susceptibility of 147 international clinical Mycobacterium abscessus isolates to epetraborole and comparators by broth microdilution.
J Antimicrob Chemother
December 2024
Division of Mycobacterial and Respiratory Infections, Department of Medicine, National Jewish Health, Denver, CO, USA.
Background: Mycobacterium abscessus is a highly drug-resistant non-tuberculous mycobacterium (NTM) for which treatment is limited by the lack of active oral antimycobacterials and frequent adverse reactions. Epetraborole is a novel oral, boron-containing antimicrobial that inhibits bacterial leucyl-tRNA synthetase, an essential enzyme in protein synthesis, and has been shown to have anti-M. abscessus activity in preclinical studies.
View Article and Find Full Text PDFYAP enhances mitochondrial OXPHOS in tumor-infiltrating Treg through upregulating Lars2 on stiff matrix.
J Immunother Cancer
November 2024
Department of Gastrointestinal Cancer Biology, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China
Background: Tumor-infiltrating regulatory T cells (TI-Tregs) are well-adapted to thrive in the challenging tumor microenvironment (TME) by undergoing metabolic reprogramming, notably shifting from glycolysis to mitochondrial oxidative phosphorylation (OXPHOS) for energy production. The extracellular matrix is an important component of the TME, contributing to the regulation of both tumor and immune cell metabolism patterns by activating mechanosensors such as YAP. Whether YAP plays a part in regulating TI-Treg mitochondrial function and the underlying mechanisms are yet to be elucidated.
View Article and Find Full Text PDFProbing the Molecular Basis of Aminoacyl-Adenylate Affinity With Mycobacterium tuberculosis Leucyl-tRNA Synthetase Employing Molecular Dynamics, Umbrella Sampling Simulations and Site-Directed Mutagenesis.
J Mol Recognit
October 2024
Department of Protein Synthesis Enzymology, Institute of Molecular Biology and Genetics, the NAS of Ukraine, Kyiv, Ukraine.
Leucyl-tRNA synthetase (LeuRS) is clinically validated molecular target for antibiotic development. Recently, we have reported several classes of small-molecular inhibitors targeting aminoacyl-adenylate binding site of Mycobacterium tuberculosis LeuRS with antibacterial activity. In this work, we performed in silico site-directed mutagenesis of M.
View Article and Find Full Text PDFNew antibacterial candidates against Acinetobacter baumannii discovered by in silico-driven chemogenomics repurposing.
PLoS One
September 2024
Molecular Bacteriology Laboratory, Institute of Tropical Pathology and Public Health, Federal University of Goiás, Goiânia, Goiás, Brazil.
Acinetobacter baumannii is a worldwide Gram-negative bacterium with a high resistance rate, responsible for a broad spectrum of hospital-acquired infections. A computational chemogenomics framework was applied to investigate the repurposing of approved drugs to target A. baumannii.
View Article and Find Full Text PDFPotential Piperolactam A Isolated From Piper betle as Natural Inhibitors of Brucella Species Aminoacyl-tRNA Synthetase for Livestock Infections: In Silico Approach.
Vet Med Sci
November 2024
Department of Chemistry, Faculty of Mathematics and Natural Sciences, Universitas Padjadjaran, Sumedang, West Java, Indonesia.
Article Synopsis
- - Brucellosis, caused by the Brucella bacterium, leads to serious economic losses in livestock due to reproductive issues and reduced milk production, coupled with antibiotic resistance complicating treatment efforts.
- - This study focuses on isolating a compound called piperolactam A from Piper betle leaves, aiming to evaluate its potential as an antibacterial agent against Brucella sp. and its mechanism of action against specific enzymes in bacteria.
- - Through molecular docking methods, the research shows that piperolactam A exhibits strong binding affinity to leucyl-tRNA synthetase (LeuRS), suggesting it could effectively inhibit bacterial growth by disrupting protein synthesis.
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