The search of new effective antibacterial drugs against infectious agents also lately include inhibitors of some aminoacyl-tRNA synthetases. In this regard, tyrosyl-tRNA synthetase from M. tuberculosis (MtTyrRS) is one of especially attractive target due to its key role in cell metabolism and significant differences between spatial structures of eubacterial and human TyrRSs. In this article the theoretic homology modeling of spatial structure of catalytic module of MtTyrRS (region Met1-Ser321) has been carried out based on experimentally determined structures of homologous TyrRSs from other eubacteria, and the comparison of the structures of their active sites was performed. Most of MtTyrRS catalytic site residues, particularly those, which form special hydrogen bonds with low-molecular-weight ligands (Tyr36, Asp80, Tyrl71, Asp178, Gly194 and Asp196) as well catalytic residues Lys231 and Lys234 from KFGK motif of interdomain loop and Arg87, are conservative in evolution.
The true prevalence rates of multidrug-resistant tuberculosis (MDRT) are unknown for most regions of Russia. This study was conducted in the Samara Region that differs from other regions in the rapid spread of HIV infection. The purpose of this study was to determine the primary and acquired resistance of Mycobacterium tuberculosis (MBT) to first-line antituberculous drugs in patients from civil and penitentiary sectors and to reveal risk factors of drug resistance of MBT. Six hundred patients (309 civilians and 291 prisoners who had been bacteriologically diagnosed as having tuberculosis. The authors have established the following:--in new cases, primary drug resistance is as follows: to isoniazid [38.9% (95% CI, 31.3-36.9%)], to rifampicin [25.9% (95% CI, 19.4-33.4%)] and to MDRT [23.0% (95% CI, 16.7-30.3%)];--in prisoners, the primary resistance of MBT was statistically more significant than in civilians;--male sex, in adequate prior or current treatment for tuberculosis for more than 4 weeks, the presence of fibrocavernous tuberculosis and previous prison stay are essential risk factors of the development of resistance of MBT to both any first-line drug and MDRT;--HIV infection is unassociated with resistance.
Common juniper, Juniperus communis, is amongst the plants most frequently used by the indigenous peoples of North America for medicinal purposes. The First Nations of the Canadian Maritimes use infusions of juniper primarily as a tonic and for the treatment of tuberculosis. Previous investigations of extracts derived from the aerial parts of J. communis have shown it to possess anti-mycobacterial activity. The aim of the study is to isolate and identify anti-mycobacterial constituents from the aerial parts of J. communis.
Methanolic extracts of J. communis needles and branches were subjected to bioassay guided fractionation using the microplate resazurin assay (MRA) to assess inhibitory activity against Mycobacterium tuberculosis strain H37Ra. The anti-mycobacterial constituents were identified by NMR, MS and polarimetry.
The diterpenes isocupressic acid and communic acid and the aryltetralin lignan deoxypodophyllotoxin were isolated from the J. communis extract. Isocupressic acid and communic acid (isolated as an inseparable 3:2 mixture of cis and trans isomers) displayed MICs of 78 µM and 31 µM and IC(50)s of 46 µM and 15 µM against M. tuberculosis H37Ra respectively. Deoxypodophyllotoxin was less active, with a MIC of 1004 µM and an IC(50) of 287 µM.
Isocupressic acid, communic acid and deoxypodophyllotoxin were identified as the principal constituents responsible for the anti-mycobacterial activity of the aerial parts of J. communis. Although further research will be required to evaluate the relative activities of the two communic acid isomers, this work validates an ethnopharmacological use of this plant by Canadian First Nations and Native American communities.
To determine baseline levels of anti-tuberculosis drug resistance in Orel Oblast.
Drug susceptibility testing (DST) records from 1 July 1999 to 30 June 2000 for patients with sputum acid-fast bacilli smear-positive pulmonary tuberculosis were reviewed. Treatment and incarceration status were obtained from the tuberculosis register. Patients with 1 month or less of prior treatment were defined as new cases; those previously treated for more than 1 month were defined as retreatment cases.
Of 246 smear-positive isolates, 212 (86%) had DST performed. Of these, 190 (90%) were from new and 22 (10%) from retreatment cases; 171 (81%) were from community and 41 (19%) were from prison patients. Any drug resistance was more common among prison than community patients (44% vs. 30%, P = 0.05). MDR-TB was found in 14 (6.6%) of 212 isolates, and was more prevalent in prison compared with community patients (12% vs. 5%, P = 0.05). Retreatment cases were more likely than new cases to have MDR-TB (prevalence ratio [PR] = 8.5, 95%CI = 3.3-22.3), although the PR was higher for prison than for community retreatment cases (10.0 vs. 5.8).
New cases with MDR-TB were less prevalent in Orel Oblast compared with other survey sites in Russia. Any drug resistance and MDR-TB were associated with prior treatment, especially in the prison population. Continued monitoring of trends in drug resistance following DOTS implementation is needed.
To estimate resistance rates of Mycobacterium tuberculosis to antituberculosis drugs in relation to previous treatment, country of origin, age and duration of residence in Canada.
Retrospective chart review of all culture-positive tuberculosis diagnosed between 1982 and 1994 in immigrants to Alberta.
A total of 753 immigrants with culture-positive tuberculosis were studied; 131 patients (17.4%, 95% Confidence Interval [CI] 14.7, 20.1) had strains resistant to one or more of the first-line medications (isoniazid [INH], rifampin [RIF], ethambutol [EMB], pyrazinamide [PZA], and streptomycin [SM]). Initial and secondary resistance rates were 16.4% and 30.3%, respectively (P = 0.003, Odds ratio [OR] 2.2, 95% CI 1.3, 3.8). Resistance occurred in 22.2% of patients 40 years of age and under, and in 13.8% of those over 40 years of age (P = 0.005, OR 1.8, 95% CI 1.2, 2.6). Resistant M. tuberculosis was isolated from 20.4% of those who had lived in Canada for less than 15 years, and in 9.0% of those who had immigrated to Canada more than 15 years before diagnosis (P