Mycobacterium tuberculosis as a model system

ABSTRACT Over the past 30 years, the study of Mycobacterium tuberculosis has become a vibrant field that supports basic investigation into mycobacteria, wide-ranging studies of M. tuberculosis pathogenesis, and drug and therapeutic development. In this minireview, we highlight the multiple ways in which M. tuberculosis is a model. M. tuberculosis has emerged as a model for prokaryotic biology, revealing basic mechanisms of gene expression, genomic integrity, and mutagenesis that expand prokaryotic dogmas established in earlier model organisms. Next, we highlight the experimental systems used to model M. tuberculosis human infection. As an obligate human pathogen, all attempts to understand the pathogenesis of TB disease seek to mimic the human infection, and a variety of systems have emerged from our field. Finally, we highlight that the M. tuberculosis field is a model for a community-driven scientific approach to a pressing global health problem for which commercial interest is limited. Our field has taken on the challenge of drug and diagnostic development, based on a foundation of expanding knowledge of basic M. tuberculosis biology, by working through academic and public/private partnerships, to make meaningful progress in therapeutics and diagnostics. Altogether, we present the M. tuberculosis field as a model for the development of a productive community that spans basic, translational, and therapeutic research, supported by public and philanthropic funding, to ultimately positively impact the treatment of human TB and the advancement of our knowledge base of microbiology and microbial pathogenesis.