Identification of genetic determinants of bedaquiline resistance in Mycobacterium tuberculosis in Ural region, Russia.

Collecting data on rare Mycobacterium tuberculosis (Mtb) clinical isolates with resistance to the new anti-tuberculosis drug bedaquiline is an important task for improving antimicrobial susceptibility testing methods. Nanopore whole genome sequencing, the proportion method on Middlebrook 7H11 medium, and BACTEC MGIT 960 assays were used to analyze genotypic and phenotypic resistance to bedaquiline. We found four mutations: atpE I66M, atpE А63Р, Rv0678 А36Т, and Rv0678 S53P in five isolates with different levels of phenotypic bedaquiline resistance. IMPORTANCE: Bedaquiline (BDQ) is a new anti-tuberculosis drug. The phenotypic and genotypic data describing the mechanism of drug resistance are critical for the design of rapid and accurate diagnostic tests. We consider that our work, which describes genotypic and phenotypic resistance to BDQ, can contribute to the standardization of drug susceptibility testing.

Optimization, characterization, and cytotoxicity studies of novel anti-tubercular agent-loaded liposomal vesicles.

The treatment of tuberculosis is still a challenging process due to the widespread of pathogen strains resistant to antibacterial drugs, as well as the undesirable effects of anti-tuberculosis therapy. Hence, the development of safe and effective new anti-antitubercular agents, in addition to suitable nanocarrier systems, has become of utmost importance and necessity. Our research aims to develop liposomal vesicles that contain newly synthesized compounds with antimycobacterial action. The compound being studied is a derivative of imidazo-tetrazine named 3-(3,5-dimethylpyrazole-1-yl)-6-(isopropylthio) imidazo [1,2-b] [1,2,4,5] tetrazine compound. Several factors that affect liposomal characteristics were studied. The maximum encapsulation efficiency was 53.62 ± 0.09. The selected liposomal formulation T8* possessed a mean particle size of about 205.3 ± 3.94 nm with PDI 0.282, and zeta potential was + 36.37 ± 0.49 mv. The results of the in vitro release study indicated that the solubility of compound I was increased by its incorporation in liposomes. The free compound and liposomal preparation showed antimycobacterial activity against Mycobacterium tuberculosis H37Rv (ATCC 27294) at MIC value 0.94-1.88 µg/ml. We predict that the liposomes may be a good candidate for delivering new antitubercular drugs.