MorphEUS: Morphological Profiling Under stress

Morphological profiling is a method to classify target pathways of antibacterials based on how bacteria respond to treatment through changes to cellular shape and spatial organization. A new technology that combines high throughput imaging and machine learning could speed discovery of drugs to fight tuberculosis.

Current treatment requires multiple drugs for at least six months and sometimes years, and antibiotic resistance is growing, increasing urgency for finding new treatments.

Here we utilized the cell-to-cell variation in morphological features of Mycobacterium tuberculosis bacilli to develop a rapid profiling platform called Morphological Evaluation and Understanding of Stress (MorphEUS).

The new technology—dubbed MorphEUS (Morphological Evaluation and Understanding of drug Stress)—provides a rapid, efficient, cost-effective way to determine how specific compounds act to destroy Mycobcterium tuberculosis (M. tb), the bacterium that causes tuberculosis,

MorphEUS classified 94% of tested drugs correctly into broad categories according to modes of action previously identified in the literature. In the other 6%, MorphEUS pointed to key off-target activities.

We anticipate that the ability of MorphEUS to rapidly identify pathways of drug action and the proximal cause of cellular damage in tubercle bacilli will make it applicable to other pathogens and cell types where morphological responses are subtle and heterogeneous.

1. Smith, Trever & Pullen, Krista & Olson, Michaela & McNellis, Morgan & Richardson, Ian & Hu, Sophia & Larkins-Ford, Jonah & Wang, Xin & Freundlich, Joel & Ando, D. & Aldridge, Bree. (2020). Morphological profiling of tubercle bacilli identifies drug pathways of action. Proceedings of the National Academy of Sciences. 202002738. 10.1073/pnas.2002738117.

2. Lakshminarayan H, Rajaram A, Narayanan S (2009) Involvement of Serine Threonine Protein Kinase, PknL, from Myco- bacterium Tuberculosis H37Rv in Starvation Response of Mycobacteria. J Microbial Biochem Technol 1: 030-036. doi:10.4172/ 1948-5948.1000006