RESUMO
The levels and spectra of the drug resistance of clinical M. tuberculosis strains were defined. There was a relationship of treatment regimens to the drug resistance of mycobacteria isolated from the strains. The fragments of genes rpoB, inhA, and katG were analyzed by polymerase chain reaction and sequencing. In addition to earlier identified substitutions, new mutations were found in rpoB: A-->T/233, G-->A/395, C-->T/232, G-->T/202, C-->T/221, C-->T/260, GA-->TT/202-203, delta 199-207 ATGGACCAG. Strain 12/7 was found to have 30 point mutations leading to substitution of only 3 amino acids and to have GGG(Gly)354 deletion as well. Most mutations in this strain are "silent". Substitutions at 944 and 463 positions were revealed in katG.
Assuntos
Antituberculosos/farmacologia , Proteínas de Bactérias/genética , DNA Bacteriano/análise , Resistência Microbiana a Medicamentos/genética , Isoniazida/farmacologia , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/genética , Rifampina/farmacologia , Antibióticos Antituberculose/farmacologia , Contagem de Colônia Microbiana , Primers do DNA/química , RNA Polimerases Dirigidas por DNA/genética , Humanos , Mycobacterium tuberculosis/crescimento & desenvolvimento , Oxirredutases/genética , Peroxidases/genética , Mutação Puntual , Reação em Cadeia da Polimerase , Tuberculose/tratamento farmacológico , Tuberculose/microbiologiaRESUMO
Recombinant fusion proteins consist of the N-terminal 488 or 513 amino acids of diphtheria toxin joined to human interleukin 2. Initially those fusion proteins were expressed in E. coli under the control of the tox promotor. Western blot analyses showed that E. coli strains bearing the hybrid genes produce 68 kDa or 72 kDa fusion proteins that retain the immunological determinants of both the diphtheria toxin component and the interleukin 2 component. The fusion protein with mol. mass 72 kDa was partially purified by affinity chromatography. The expression of the fusion proteins under the control of the strong promotors was increased (100-fold for tac- promotor) compared to that under the control of the tox promotor. DT-IL2 might be a useful cytotoxic agent in the treatment of diseases involving IL2 receptor-positive cells, such as allograft rejection, graft-versus-host disease, multiple sclerosis et al.
