Drug Degradation Caused by Mutations Confers Contezolid (MRX-I) Resistance in Mycobacterium tuberculosis.

Contezolid (MRX-I), a safer antibiotic of the oxazolidinone class, is a promising new antibiotic with potent activity against Mycobacterium tuberculosis (MTB) both and . To identify resistance mechanisms of contezolid in MTB, we isolated several spontaneous contezolid-resistant MTB mutants, which exhibited 16-fold increases in the MIC of contezolid compared with the parent strain but were still unexpectedly susceptible to linezolid. Whole-genome sequencing revealed that most of the contezolid-resistant mutants bore mutations in the gene, which encodes a transcriptional repressor.

Fitness Cost and Compensatory Evolution in Levofloxacin-Resistant .

We isolated spontaneous levofloxacin-resistant strains of to study the fitness cost and compensatory evolution of fluoroquinolone resistance in mycobacteria. Five of six mutant strains with substantial growth defects showed restored fitness after being serially passaged for 18 growth cycles, along with increased cellular ATP level. Whole-genome sequencing identified putative compensatory mutations in the gene that restored the fitness of the resistant strains, presumably by altering the bacterial energy metabolism.

Ring-opening formal hetero-[5+2] cycloaddition of 1-tosyl-2,3-dihydro-1H-pyrroles with terminal alkynes: entry to 1-tosyl-2,3-dihydro 2,3-dihydro-1H-azepines.

A new Lewis acid catalysed formal hetero-[5+2] cycloaddition of 2,3-dihydro-1H-pyrroles to terminal alkynes is described. By employing a FeCl3 and BF3·OEt2 co-catalytic strategy, the ring-opening of 1-tosyl-2,3-dihydro-1H-pyrroles by selective cleavage of the C(sp2)-N bond and subsequent annulation have been achieved to access 1-tosyl-2,3-dihydro-1H-azepines with excellent regioselectivity, offering a new avenue for cycloaddition through the ring-opening of non-strained-ring-based units.

Characterization of linezolid-resistance-associated mutations in Mycobacterium tuberculosis through WGS.

Objectives: Linezolid is becoming an important antibiotic for treating MDR/XDR TB, but the mutations conferring resistance to linezolid remain inadequately characterized. Herein, we investigated the linezolid-resistance-associated mutations on a whole-genome scale through parallel selections of resistant isolates in vitro.

Methods: Ten parallel Mycobacterium tuberculosis H37Rv cultures were subjected to spontaneous mutant selection on 7H11 agar plates containing 2.

Rhodium-Catalyzed Annulation of 4-Arylbut-3-yn-1-amines with Internal Alkynes through C-H Functionalization.

A new, one-step rhodium(III)-catalyzed annulation of 4-arylbut-3-yn-1-amines with internal alkynes through C-H functionalization is reported. This reaction allows the formation of three new chemical bonds, including two C-C bonds and one C-N band, thus selectively assembling various spiro[indene-1,2'-pyrrolidine]s with excellent functional group compatibility, high atom-economy, and step-efficiency.

Characterization of mutations in streptomycin-resistant Mycobacterium tuberculosis isolates in Sichuan, China and the association between Beijing-lineage and dual-mutation in gidB.

Mutations in rpsL, rrs, and gidB are well linked to streptomycin (STR) resistance, some of which are suggested to be potentially associated with Mycobacterium tuberculosis genotypic lineages in certain geographic regions. In this study, we aimed to investigate the mutation characteristics of streptomycin resistance and the relationship between the polymorphism of drug-resistant genes and the lineage of M. tuberculosis isolates in Sichuan, China.

Rhodium(III)-catalyzed oxidative bicyclization of 4-arylbut-3-yn-1-amines with internal alkynes through C-H functionalization.

A new Rh(iii)-catalyzed oxidative bicyclization through C-H functionalization is presented. This reaction allows the selective assembly of diverse benzo[g]indoles from 4-arylbut-3-yn-1-amines and internal alkynes via a sequence of aromatic C(sp(2))-H functionalization, cyclodimerization and nucleophilic cyclization.

Mixed Infections and Rifampin Heteroresistance among Mycobacterium tuberculosis Clinical Isolates.

Mixed infections and heteroresistance of Mycobacterium tuberculosis contribute to the difficulty of diagnosis, treatment, and control of tuberculosis. However, there is still no proper solution for these issues. This study aimed to investigate the potential relationship between mixed infections and heteroresistance and to determine the high-risk groups related to these factors.

Rhodium(III)-Catalyzed [3+2]/[5+2] Annulation of 4-Aryl 1,2,3-Triazoles with Internal Alkynes through Dual C(sp2)-H Functionalization.

A rhodium(III)-catalyzed [3+2]/[5+2] annulation of 4-aryl 1-tosyl-1,2,3-triazoles with internal alkynes is presented. This transformation provides straightforward access to indeno[1,7-cd]azepine architectures through a sequence involving the formation of a rhodium(III) azavinyl carbene, dual C(sp(2))-H functionalization, and [3+2]/[5+2] annulation.

Rhodium(III)-catalyzed [3+2] annulation of 5-aryl-2,3-dihydro-1H-pyrroles with internal alkynes through C(sp²)-H/alkene functionalization.

This study describes a new rhodium(III)-catalyzed [3+2] annulation of 5-aryl-2,3-dihydro-1H-pyrroles with internal alkynes using a Cu(OAc)2 oxidant for building a spirocyclic ring system, which includes the functionalization of an aryl C(sp(2))-H bond and addition/protonolysis of an alkene C=C bond. This method is applicable to a wide range of 5-aryl-2,3-dihydro-1H-pyrroles and internal alkynes, and results in the assembly of the spiro[indene-1,2'-pyrrolidine] architectures in good yields with excellent regioselectivities.