Kanamycin and Ofloxacin Activate the Intrinsic Resistance to Multiple Antibiotics in .

Drug resistance (DR) in is the main problem in fighting tuberculosis (TB). This pathogenic bacterium has several types of DR implementation: acquired and intrinsic DR. Recent studies have shown that exposure to various antibiotics activates multiple genes, including genes responsible for intrinsic DR.

MmpS5-MmpL5 Transporters Provide Resistance to imidazo[1,2-][1,2,4,5]tetrazines.

The emergence and spread of drug-resistant strains (including MDR, XDR, and TDR) force scientists worldwide to search for new anti-tuberculosis drugs. We have previously reported a number of imidazo[1,2-][1,2,4,5]tetrazines - putative inhibitors of mycobacterial eukaryotic-type serine-threonine protein-kinases, active against . Whole genomic sequences of spontaneous drug-resistant mutants revealed four genes possibly involved in imidazo[1,2-][1,2,4,5]tetrazines resistance; however, the exact mechanism of resistance remain unknown.

Sequencing and Analysis of Three Mycobacterium tuberculosis Genomes of the B0/N-90 Sublineage.

We report the draft genome sequences of three isolates belonging to the B0/N-90 sublineage, EKB34, EKB53, and EKB79. The B0/N-90 sublineage belongs to the prevalent (in Russia) and highly virulent Beijing-B0/W148 sublineage. Isolates EKB34 and EKB79 were obtained from people with immune deficiency.

Synthesis and antimycobacterial activity of imidazo[1,2-b][1,2,4,5]tetrazines.

Tuberculosis (TB) has recently become the leading killer among infectious diseases. Multidrug and extensively drug-resistant Mycobacterium tuberculosis strains urge the need to develop anti-TB drugs with a novel mechanism of action. We describe synthesis of 22 novel imidazo[1,2-b][1,2,4,5]tetrazine derivatives with different substituents at C(3) and C(6) positions, and their antimycobacterial activity in vitro.

Draft Genome Sequences of 12 Strains Resistant to Imidazo[1,2-][1,2,4,5]Tetrazines.

Here, we report 12 draft genome sequences of mutant strains resistant to imidazo[1,2-][1,2,4,5]tetrazines, which are antituberculosis drug candidates. We have identified 7 different mutations in the MSMEG_1380 gene, which encodes the AcrR/TetR_N transcriptional repressor, which may activate efflux-mediated resistance.

Mutations in Efflux Pump Rv1258c (Tap) Cause Resistance to Pyrazinamide, Isoniazid, and Streptomycin in .

Although drug resistance in is mainly caused by mutations in drug activating enzymes or drug targets, there is increasing interest in the possible role of efflux in causing drug resistance. Previously, efflux genes have been shown to be upregulated upon drug exposure or implicated in drug resistance in overexpression studies, but the role of mutations in efflux pumps identified in clinical isolates in causing drug resistance is unknown. Here we investigated the role of mutations in efflux pump Rv1258c (Tap) from clinical isolates in causing drug resistance in We constructed point mutations V219A and S292L in Rv1258c in the chromosome of and the point mutations were confirmed by DNA sequencing.

Resistance to pyrazinamide in Russian Mycobacterium tuberculosis isolates: pncA sequencing versus Bactec MGIT 960.

Resistance to pyrazinamide (PZA) may impact clinical outcome of anti-tuberculosis chemotherapy. PZA susceptibility testing using MGIT 960 is not reliable and little information is available on the prevalence of PZA resistance in Russia. A collection of 64 clinical isolates of Mycobacterium tuberculosis, including 35 multidrug resistant and extensively drug-resistant (MDR/XDR), was analyzed for PZA resistance using MGIT 960, Wayne test, and sequencing of PZA resistance genes pncA, rpsA and panD.