Synthesis and Antimycobacterial Assays of Some New Ethambutol Analogs

Molecules, Journal Year: 2025, Volume and Issue: 30(3), P. 600 - 600

Published: Jan. 29, 2025

Ethambutol (EMB) is a first-line anti-tuberculosis drug that also considered in treatment regimens for infections caused by non-tuberculous mycobacteria (NTM). EMB targets the arabinosyl transferases EmbCAB, which are important synthesis of cell wall constituents. To further explore and narrow down structural variability EMB, we synthesized three series new analogs. We tested their activity against Mycobacterium tuberculosis, smegmatis, abscessus intracellulare. Only analogs very closely resembled showed comparable antimycobacterial activity.

Language: Английский

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Recent advances in research on Mycobacterium tuberculosis virulence factors and their role in pathogenesis

Journal of Microbiology Immunology and Infection, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Mycobacterium tuberculosis (Mtb) is the causative agent of (TB) in humans and animals. Mtb invades host's lungs via airborne transmission, infecting macrophages causing TB. In some cases, infection can spread to other tissues organs. Despite availability several drugs for TB treatment, emergence multidrug-resistant has led high morbidity mortality rates worldwide. Therefore, it urgent discover new anti-tuberculosis more effective treatment. Recent studies have shown that virulence factors play a crucial role its pathogenicity. By evading immune surveillance through mechanisms such as anti-oxidative stress, nutrient synthesis metabolism, apoptosis host cells, achieve long-term survival host. Understanding pathogenicity will aid development vaccines drugs. this review, we summarize latest research progress on provide reference targeted

Language: Английский

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Dual Mutations in MSMEG_0965 and MSMEG_1380 Confer High-Level Resistance to Bortezomib and Linezolid by Both Reducing Drug Intake and Increasing Efflux in Mycobacterium smegmatis

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(8), P. 3779 - 3779

Published: April 17, 2025

The emergence of multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis strains poses serious challenges to global control, highlighting the urgent need elucidate mechanisms underlying multidrug resistance. In this study, we screened for spontaneous bortezomib (BTZ)-resistant smegmatis (Msm) mutants identified a strain, Msm-R1-2, exhibiting 16- 64-fold increases in minimum inhibitory concentrations (MICs) BTZ linezolid (LZD), respectively, compared parental strain. Whole-genome sequencing revealed resistance-associated mutations two functionally distinct genes: MSMEG_1380, encoding transcriptional regulator involved efflux pump expression, MSMEG_0965, porin protein. CRISPR-Cpf1-assisted gene knockout editing experiments confirmed that single either MSMEG_1380 or MSMEG_0965 caused low-level resistance (4-fold MIC increase) LZD, while dual conferred levels comparable with MICs respectively. An ethidium bromide accumulation assay demonstrated reduce cell wall permeability, contributing Furthermore, quantitative real-time PCR showed upregulate mmpS5-mmpL5 system. Together, these function synergistically: restricted drug entry combined enhanced confers robust These findings provide novel insights into evolutionary mycobacteria.

Language: Английский

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Tuberculosis: Hemoptysis with Unexplained Fevers and Weight Loss

Published: Jan. 1, 2025

Language: Английский

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