Screening and Characterization of Mutations in Isoniazid-Resistant Mycobacterium tuberculosis Isolates Obtained in Brazil

Abstract

We investigated mutations in the genesIsoniazid (INH), a first-line antituberculosis drug, is bactericidal and has a simple chemical structure consisting of a pyridine ring and a hydrazide group. INH is a prodrug that enters actively growing tubercle bacilli by passive diffusion (2). The bifunctional bacterial enzyme catalase-peroxidase (KatG) converts INH to a range of oxygenated and organic toxic radicals that attack multiple targets in the mycobacterial cell (35,36,48). The best-characterized target of these radicals is the cell wall mycolic acid, but DNA, carbohydrates, lipids, and NAD metabolism may be targeted as well (16,36,50).The tuberculosis case rate in Brazil is the 15th highest in the world, with an estimated prevalence of 64 cases per 100,000 population; moreover, ϳ0.9% of the new cases are multidrug resistant (45). A recent nationwide investigation of primary INH resistance found a national frequency of 3.8% (29); however, the percentages varied greatly between geographic regions of the country.

Predictive Value of Molecular Drug Resistance Testing of Mycobacterium tuberculosis Isolates in Valle del Cauca, Colombia

“…In our study, both susceptible and resistant, mainly MDR, M. tuberculosis strains were evaluated; unfortunately, only a limited number of strains resistant to second-line drugs were evaluated. We found the performance of the GenoType tests in Colombia to be similar to or even better than those described in studies elsewhere, like in Mexico, Brazil, Peru, Chile, Bolivia, France, Italy, Turkey, Spain, Vietnam, the Russian Federation, Ethiopia, and China (4,(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23). In general, sensitivity, specificity, positive and negative predictive values, and concordance with phenotypic DST support the utility of these tests for the screening of resistance to first-and second-line antituberculosis drugs in our country.…”

“…Specifically, the frequency of the katG MUT S315T1 in Latin America varied, with 52% in Mexico, 61.9% in Brazil, 71.2% in Peru, and 88% in Colombia (12)(13)(14). In comparison, the frequency in some countries on other continents was 65% in France, 66.5% in Italy, 73% in Turkey, 87% in Spain, 88% in Vietnam, 94% in the Russian Federation, and 94% in Ethiopia (17)(18)(19)(20)(21)(22)(23).…”

Pt(II) and Ag(I) complexes with acesulfame: Crystal structure and a study of their antitumoral, antimicrobial and antiviral activities

“…A total of 1.6 million people died of tuberculosis, including 190,000 patients infected with HIV [19]. Despite the discovery of new drugs and the improvement of tuberculosis treatment, such disease is severely affected by the development of multi-drug resistant M. tuberculosis strains [20,21].…”

Resistência do Mycobacterium tuberculosis à isoniazida por mutações em duas regiões diferentes do gene katG

“…This shows that the mutations that caused INH resistance occurred outside the regions of the katG gene studied or occurred in other genes. (23) In region 1, there were a large number of insertions and deletions, resulting in an amino acid change in the protein, reduced catalase levels and INH resistance. In 24 strains, we found a new allele, which has not been previously described, generated by the deletion of the last adenine nucleotide at codon 4, region 1.…”