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|Title:||Correlations of mutations in katG, oxyR-ahpC and inhA genes and in vitro susceptibility in Mycobacterium tuberculosis clinical strains segregated by spoligotype families from tuberculosis prevalent countries in South America||Authors:||Dalla Costa, Elis R.
Ribeiro, Marta O.
Silva, Márcia S. N.
Arnold, Liane S.
Rostirolla, Diana C.
Cafrune, Patricia I.
Espinoza, Roger C.
Telles, María A.
Suffys, Philip N.
Lopes, Maria L.
Campelo, Creuza L.
Miranda, Silvana S.
Almeida da Silva, Pedro E.
de Souza Fonseca, Leila
Ho, John L.
Kritski, Afrânio L.
Rossetti, María L.
|Keywords:||Mycobacterium tuberculosis;Mutación;Tuberculosis;Rifampin;Estreptomicina;Genes;América del Sur||Issue Date:||2009||Description:||Background Mutations associated with resistance to rifampin or streptomycin have been reported for W/Beijing and Latin American Mediterranean (LAM) strain families of Mycobacterium tuberculosis. A few studies with limited sample sizes have separately evaluated mutations in katG, ahpC and inhA genes that are associated with isoniazid (INH) resistance. Increasing prevalence of INH resistance, especially in high tuberculosis (TB) prevalent countries is worsening the burden of TB control programs, since similar transmission rates are noted for INH susceptible and resistant M. tuberculosis strains. Results We, therefore, conducted a comprehensive evaluation of INH resistant M. tuberculosis strains (n = 224) from three South American countries with high burden of drug resistant TB to characterize mutations in katG, ahpC and inhA gene loci and correlate with minimal inhibitory concentrations (MIC) levels and spoligotype strain family. Mutations in katG were observed in 181 (80.8%) of the isolates of which 178 (98.3%) was contributed by the katG S315T mutation. Additional mutations seen included oxyR-ahpC; inhA regulatory region and inhA structural gene. The S315T katG mutation was significantly more likely to be associated with MIC for INH ≥2 μg/mL. The S315T katG mutation was also more frequent in Haarlem family strains than LAM (n = 81) and T strain families. Conclusion Our data suggests that genetic screening for the S315T katG mutation may provide rapid information for anti-TB regimen selection, epidemiological monitoring of INH resistance and, possibly, to track transmission of INH resistant strains.
Fil: Dalla Costa, Elis R. State Foundation for Production and Research in Health (FEPPS); Brasil.
Fil: Ribeiro, Marta O. State Foundation for Production and Research in Health (FEPPS); Brasil.
Fil: Silva, Márcia S. N. State Foundation for Production and Research in Health (FEPPS); Brasil.
Fil: Arnold, Liane S. State Foundation for Production and Research in Health (FEPPS); Brasil.
Fil: Rostirolla, Diana C. State Foundation for Production and Research in Health (FEPPS); Brasil.
Fil: Cafrune, Patricia I. State Foundation for Production and Research in Health (FEPPS); Brasil.
Fil: Espinoza, Roger C. Blufstein Clinic Laboratory; Perú.
Fil: Palaci, Moises. Federal University of Espírito Santo; Brasil.
Fil: Telles, Maria A. Adolfo Lutz Institute; Brasil.
Fil: Ritacco, Viviana. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Infecciosas. Servicio de Micobacterias; Argentina.
Fil: Suffys, Philip N. Oswaldo Cruz Institute; Brasil.
Fil: Lopes, Maria L. Evandro Chagas Institute; Brasil.
Fil: Campelo, Creuza L. LACEN Ceará; Brasil
Fil: Miranda, Silvana S. Federal University of Minas Gerais; Brasil.
Fil: Kremer, Kristin. National Institute for Public Healthand the Environment (RIVM). Mycobacteria Reference Unit (CIb-LIS); Países Bajos.
Fil: Almeida da Silva, Pedro E. Federal Foundation of Rio Grande; Brasil.
Fil: de Souza Fonseca, Leila. Federal University of Rio de Janeiro. Tuberculosis Academic Program; Brasil.
Fil: Ho, John L. Cornell University; Estados Unidos.
Fil: Kritski, Afrânio L. Federal University of Rio de Janeiro. Tuberculosis Academic Program; Brasil.
Fil: Rossetti, María L. R. State Foundation for Production and Research in Health (FEPPS); Brasil.
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