Resist那ncia do Mycobacterium tuberculosis 角 isoniazida por mutaˋˋes em duas regiˋes diferentes do gene katG

作者：Siqueira; Helio Ribeiro de; Freitas; Flavia Alvim Dutra de; Oliveira; Denise Neves de; Barreto; Angela Maria Werneck; Dalcolmo; Margareth Pretti; Albano; Rodolpho Mattos

来源：Jornal Brasileiro de Pneumologia, 2009, 35(8): 773-779.

DOI：10.1590/S1806-37132009000800009

• isoniazid
• mutation
• tuberculosis
• drug resistance
• multiple.

objective: to analyze and compare the mutations in two different regions of the katg gene, which is responsible for isoniazid (inh) resistance. methods: we analyzed 97 multidrug-resistant mycobacterium tuberculosis strains isolated in cultures of sputum samples obtained from the professor h谷lio fraga referral center, in bras赤lia, brazil. another 6 inh-sensitive strains did not present mutations and were included as controls. we used pcr to amplify two regions of the katg gene (genbank accession no. u06258)-region 1, (from codon 1 to codon 119) and region 2 (from codon 267 to codon 504)-which were then sequenced in order to identify mutations. results: seven strains were resistant to inh and did not contain mutations in either region. thirty strains carried mutations in region 1, which was characterized by a high number of deletions, especially at codon 4 (24 strains). region 2 carried 83 point mutations, especially at codon 315, and there was a serine-to-threonine (agc-to-acc) substitution in 73 of those cases. the analysis of region 2 allowed inh resistance to be diagnosed in 81.4% of the strains. nine strains had mutations exclusively in region 1, which allowed the proportion of inh-resistant strains identified to be increased to 90.6%. conclusions: the number of mutations at codon 315 was high, which is consistent with cases described in brazil and in other countries, and the analysis of region 1 resulted in a 9.2% increase in the rate at which mutations were identified.