contribution of efflux to the emergence of isoniazid and multidrug resistance in mycobacterium tuberculosis流出的贡献在结核分枝杆菌异烟肼和多药耐药性的出现.pdf

Contribution of Efflux to the Emergence of Isoniazid and Multidrug Resistance in Mycobacterium tuberculosis 1 1,2 ˜ ˜ 3 1 3 4 Diana Machado , Isabel Couto , Joao Perdigao , Liliana Rodrigues , Isabel Portugal , Pedro Baptista , Bruno Veigas4, Leonard Amaral1,5, Miguel Viveiros1,5* ´ ´ 1 Grupo de Micobacterias, Unidade de Microbiologia Medica, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa (IHMT/UNL), Lisboa, Portugal, ´ ˆ ´ 2 Centro de Recursos Microbiologicos (CREM), Faculdade de Ciencias e Tecnologia, Universidade Nova de Lisboa, Caparica, Portugal, 3 Centro de Patogenese Molecular/ ´ ˆ ˆ URIA, Faculdade de Farmacia, Universidade de Lisboa, Lisboa, Portugal, 4 CIGMH, Departamento de Ciencias da Vida, Faculdade de Ciencias e Tecnologia, Universidade Nova de Lisboa, Caparica, Portugal, 5 COST ACTION BM0701 (ATENS), Brusells, Belgium Abstract Multidrug resistant (MDR) tuberculosis is caused by Mycobacterium tuberculosis resistant to isoniazid and rifampicin, the two most effective drugs used in tuberculosis therapy. Here, we investigated the mechanism by which resistance towards isoniazid develops and how overexpression of efflux pumps favors accumulation of mutations in isoniazid targets, thus establishing a MDR phenotype. The study was based on the in vitro induction of an isoniazid resistant