Mycobacterium tuberculosis genotypes and their relationships with clinical and immunological phenotypes in Singapore

Abstract

This project aimed primarily to discover the genetic diversity of M. tuberculosis (MTB) in Singapore and to clinically and immunologically characterize tuberculosis associated with the MTB Beijing genotype. By population-based genotyping studies using three most widely used MTB genotyping modalities, we found that all the seven major globally prevalent genotypes were present in Singapore and Beijing strains accounted for >50% of clinical cases. Beijing strains were associated with relapse and drug-resistance. In a prospective study, we found that tuberculosis caused by Beijing strains were less frequent in fever, night sweats, and cavitary disease. By comparing Th1 and Th2 cytokine gene expressions of patients infected with Beijing and non-Beijing strains, an increased IL-4 gene expression was observed in the non-Beijing group. Our data suggest that non-Beijing instead of Beijing strains are associated with more severe disease. Increased IL-4 production might be related with the more severe disease of non-Beijing strains.