Reference Set of Mycobacterium tuberculosis Clinical Strains: A tool for research and product development

The Mycobacterium tuberculosis complex (MTBC) causes tuberculosis (TB) in humans and various other mammals. The human-adapted members of the MTBC comprise seven phylogenetic lineages that differ in their geographical distribution. There is growing evidence that this phylogenetic diversity modulates the outcome of infection and disease. For decades, TB research has focused on the two canonical MTBC reference strains H37Rv and Erdman, both of which belong to Lineage 4. Relying on only a few laboratory-adapted strains can be misleading as study results might not be directly transferrable to clinical settings where patients are infected with a phylogenetically diverse array of strains, including drug-resistant variants. This is particularly relevant for the development of new tools and strategies to control TB that ideally should be globally effective. Here, we argue for the need to expand TB research and development by incorporating the phylogenetic diversity of the MTBC. To facilitate such work, we have assembled a group of diverse clinical strains representative of the known phylogenetic diversity of the human-adapted MTB. This “MTBC clinical strains reference set”, provides a standardized resource for the TB community, which will allow for more direct comparisons between studies performed using different experimental settings and as well as better integration of multiple types of data. This strain set comprises 20 genetically well-characterized clinical strains and covers all seven human-adapted MTBC lineages. We anticipate that the in-depth analysis of this reference strain set will increase our understanding of TB biology and also assist the development of new control tools that are universally effective.