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Mycobacterium tuberculosis as a model system | Journal of Bacteriology
We are thrilled to contribute an installment in this series on microbial model systems to the Journal of Bacteriology. In launching this series (1), the editors envisioned that each installment could serve as an introduction to a field for the major bacterial model systems. In this sense, writing this installment on Mycobacterium tuberculosis (Mtb) presents some great opportunities and some challenges. There are already two excellent installments in this series covering Mycobacterium smegmatis (2) and Mycobacterium marinum (3), and we refer the reader to these reviews for related insights on the use of these mycobacteria as models. The most substantive challenge is to define how M. tuberculosis is a model, and what is it a model for? In considering these challenges, we have chosen to highlight several different interpretations of “M. tuberculosis as model.” We first consider M. tuberculosis as a model system for prokaryotic biology and emphasize the areas for which the study of Mtb has expanded prokaryotic dogmas established from the earlier model systems of Escherichia coli and Bacillus subtilis. Second, we consider experimental systems that seek to model the pathogenesis of tuberculosis as a human disease. As an obligate human pathogen, all attempts to use surrogate systems are ultimately imperfect models of the human infection. Finally, we highlight the ways in which M. tuberculosis, as a global pathogen with massive disease burden but little commercial interest in therapeutic development, has been a model for public-private partnerships in drug and diagnostic development, with notable successes that can be a model for other fields. Common to all of these interpretations of “Mtb as model” are two inescapable microbiologic features that impact all experimental work with Mtb: its slow growth rate and its requirement for BSL3 containment. Due to the nature of the broad scope of biology covered in this review, we apologize for our inability to cite all the excellent work that our field has contributed to the bacteriology literature over the past decades.