Genetic diversity and resistance to anti-tuberculosis drugs of Mycobacterium tuberculosis in China

Abstract : This thesis describes the geographical distribution of Mycobacterium tuberculosis genotypes in a major part of China and a study on the possible correlation with BCG vaccination and drug-resistance. The prevalence of drug resistance was investigated in 10 provinces, and drug resistance mutations in M. tuberculosis related to rifampicin and INH resistance were determined. The distribution of different genotypes of M. tuberculosis was investigated by using spoligotyping, large sequence polymorphism, and MLVA typing. The Beijing genotype represented 55 to 93% of the strains in the different provinces examined, with a gradient from South to North of China. Several other genotype families of M. tuberculosis were identified all belonging to the so-called "Modern" clade. Two of them, the China 2 and China 3 families, appear to be highly specific for China. Some members of the Central Asian family were found in one province whereas a possibly more ancestral strain was traced in another. The prevalence of drug resistance was determined among more than 2000 isolates from 10 provinces. Resistance against at least one drug was found in 45% of the isolates and MDR in about 29%. In China, no correlation was observed between the Beijing genotype and resistance/BCG vaccination, which is different from results in other countries. The distribution of the mutations in the rpoB gene of rifampicin resistant strains was determined. In addition, in INH resistant strains, the distribution of mutation in several genes was analysed. No mutation was detected in the oxyR and ahpC genes. This is the first time that such a large scale study is performed on the genetic diversity and drug resistance mechanisms of M. tuberculosis in China.
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Kanglin Wan. Genetic diversity and resistance to anti-tuberculosis drugs of Mycobacterium tuberculosis in China. Bacteriology. Université Paris Sud - Paris XI, 2007. English. ⟨NNT : 2007PA112140⟩. ⟨tel-00734513⟩

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