Researchers discovered that tuberculosis bacteria may grow in previously unknown patterns, potentially explaining why the disease is difficult to treat, according to a new study.

In the study, published in Nature Microbiology, the researchers from Tufts University and collaborating institutions used time-lapse imaging to uncover that Mycobacterium tuberculosis (Mtb) exhibits linear growth at the single-cell level, unlike the exponential growth observed in most other bacteria. This growth mode persisted across acidic and neutral conditions.

The researchers analyzed 363 cells out of about 2,700 imaged across triplicate experiments using advanced microfluidic devices and fluorescent labeling techniques. They observed that Mtb grows from the old cell pole first, the new pole first, or both poles simultaneously—termed NETO (new end take-off), OETO (old end take-off), and BEITO (both ends immediately take-off). Nearly 50% of cells exhibited the BEITO pattern.

The study revealed substantial heterogeneity in growth characteristics. For instance, interdivision time varied widely with a coefficient of variation (CV) of 28%, significantly higher than in related species like Mycobacterium smegmatis (21%). Median cell size at birth was 2.3 μm, doubling to 4.5 μm at division.

The findings may challenge current models of bacterial growth based on other species, suggesting that Mtb's unique growth behaviors may contribute to its ability to evade drugs and host defenses. While specific therapeutic applications were not tested, this baseline understanding of Mtb's growth heterogeneity could inform future drug development strategies.