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Whole genome CRISPRi screening identifies druggable vulnerabilities in an isoniazid resistant strain of Mycobacterium tuberculosis.
Nat Commun
November 2024
Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
Article Synopsis
- Drug-resistant Mycobacterium tuberculosis, especially mutants resistant to isoniazid, creates significant global health challenges due to mutations in the katG gene, affecting a crucial enzyme.
- Researchers employed CRISPRi, transcriptomics, and metabolomics to identify metabolic and transcriptional changes in an isoniazid-resistant katG mutant, revealing new weaknesses in processes like respiration and ribosome biogenesis.
- The study indicates that these identified vulnerabilities could be targeted for therapeutic strategies, offering potential improvements in treatment effectiveness against drug-resistant tuberculosis strains.
evolution from monoresistance to pre-extensive drug resistance during a prolonged household outbreak.
J Clin Tuberc Other Mycobact Dis
December 2024
Laboratorio de Interacciones Hospedero-Patógeno/Unidad de Biología Molecular, Institut Pasteur de Montevideo, Montevideo, Uruguay.
Whole genome sequencing (WGS) is sensitive tool for the analysis of tuberculosis transmission and drug-resistance. We used WGS to analyze the evolution from isoniazid monoresistance to MDR/preXDR during a prolonged household outbreak. The outbreak started with a isoniazid resistant strain (katG S315T mutation) and evolve in two cases to pre-XDR phenotype (with mutations in katG, rpoB, embB, pncA and gyrA genes).
View Article and Find Full Text PDFGenetic diversities and drug resistance in Mycobacterium bovis isolates from zoonotic tuberculosis using whole genome sequencing.
BMC Genomics
November 2024
Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Cairo, Egypt.
Article Synopsis
- The study investigated the genomics of zoonotic human tuberculosis caused by Mycobacterium bovis (M. bovis), focusing on virulence and drug resistance using whole-genome sequencing (WGS).
- Five strains of M. bovis were isolated from patients, all belonging to the same spoligotype and showing resistance to multiple antibiotics, indicating significant drug resistance.
- Phylogenetic analysis demonstrated genetic ties between the sequenced strains and previously identified strains from cows and humans in different countries, suggesting interconnectedness in the spread of the bacteria.
Exploring gene mutations and multidrug resistance in Mycobacterium tuberculosis: a study from the Lung Hospital in Vietnam.
Mol Biol Rep
October 2024
Institute of Genome Research, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, 100000, Vietnam.
Background: Drug-resistant tuberculosis not only diminishes treatment efficacy but also heightens the risk of transmission and mortality. Investigating Mycobacterium tuberculosis resistance to first-line antituberculosis drugs is essential to tackle a major global health challenge.
Methods And Results: Using Sanger sequencing, this study investigates gene mutations associated with multidrug resistance in drug-resistant M.
Contribution of direct InhA inhibitors to novel drug regimens in a mouse model of tuberculosis.
Antimicrob Agents Chemother
November 2024
Center for Tuberculosis Research, Division of Infectious Diseases, Johns Hopkins University, Baltimore, Maryland, USA.
Isoniazid is an important first-line medicine to treat tuberculosis (TB). Isoniazid resistance increases the risk of poor treatment outcomes and development of multidrug resistance, and is driven primarily by mutations involving , encoding the prodrug-activating enzyme, rather than its validated target, InhA. The chemical tractability of InhA has fostered efforts to discover direct inhibitors of InhA (DIIs).
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