Correlations of mutations in katG, oxyR-ahpC and inhA genes and in vitro susceptibility in Mycobacterium tuberculosisclinical strains segregated by spoligotype families from tuberculosis prevalent countries in South America

BMC Microbiology - Tập 9 - Trang 1-11 - 2009
Elis R Dalla Costa1,2, Marta O Ribeiro1, Márcia SN Silva1,3, Liane S Arnold1, Diana C Rostirolla1, Patricia I Cafrune1,4, Roger C Espinoza5, Moises Palaci6, Maria A Telles7, Viviana Ritacco8, Philip N Suffys9, Maria L Lopes10, Creuza L Campelo11, Silvana S Miranda12, Kristin Kremer13, Pedro E Almeida da Silva14, Leila de Souza Fonseca2, John L Ho15, Afrânio L Kritski2, Maria LR Rossetti1,3,16
1State Foundation for Production and Research in Health (FEPPS), Porto Alegre, Brazil
2Tuberculosis Academic Program – Federal University of Rio de Janeiro, UFRJ, Brazil
3Luterana University of Brazil, ULBRARS, Brazil
4Federal University of Rio Grande do Sul (UFRGS), Brazil
5Blufstein Clinic Laboratory, LCB, Peru
6Federal University of Espírito Santo, UFES, Brazil
7Adolfo Lutz Institute, IAL, São Paulo, Brazil
8Servicio de Micobacterias, Instittuto Nacional Enfermedades Infecciosas, ANLIS, Argentina
9Oswaldo Cruz Institute – FIOCRUZ, Rio de Janeiro, Brazil
10Evandro Chagas Institute, IEC, Manaus, Brazil
11LACEN Ceará, Brazil
12Federal University of Minas Gerais, Brazil
13Mycobacteria Reference Unit (CIb-LIS), National Institute for Public Health and the Environment (RIVM), the Netherlands
14Federal Foundation of Rio Grande, FURG, Brazil
15Cornell University, Ithaca, New York USA
16Centro de Desenvolvimento Científico e Tecnológico (CDCT), Fundação Estadual de Produção e Pesquisa em Saúde (FEPPS), Av Ipiranga, 5400 3° andar, Porto Alegre, Brazil

Tóm tắt

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. 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. 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.

Tài liệu tham khảo

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