Unknown

Dataset Information

0

Morphological profiling of tubercle bacilli identifies drug pathways of action.


ABSTRACT: 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. 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). 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 observed cell wall damage induced by bedaquiline and moxifloxacin through secondary effects downstream from their main target pathways. We implemented MorphEUS to correctly classify three compounds in a blinded study and identified an off-target effect for one compound that was not readily apparent in previous studies. 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.

SUBMITTER: Smith TC 

PROVIDER: S-EPMC7414088 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

Morphological profiling of tubercle bacilli identifies drug pathways of action.

Smith Trever C TC   Pullen Krista M KM   Olson Michaela C MC   McNellis Morgan E ME   Richardson Ian I   Hu Sophia S   Larkins-Ford Jonah J   Wang Xin X   Freundlich Joel S JS   Ando D Michael DM   Aldridge Bree B BB  

Proceedings of the National Academy of Sciences of the United States of America 20200717 31


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. Here we utilized the cell-to-cell variation in morphological features of <i>Mycobacterium tuberculosis</i> bacilli to develop a rapid profiling platform called Morphological Evaluation and Understanding of Stress (MorphEUS). MorphEUS classified 94% of tested drugs correctly into broad categories according to modes  ...[more]

Similar Datasets

| S-EPMC4707939 | biostudies-literature
| S-EPMC2945688 | biostudies-literature
| S-EPMC7754162 | biostudies-literature
| S-EPMC2862080 | biostudies-literature
| S-EPMC2809243 | biostudies-literature
| S-EPMC8433531 | biostudies-literature
| S-EPMC7302203 | biostudies-literature
| S-EPMC9685343 | biostudies-literature
2015-10-10 | GSE62506 | GEO
| S-EPMC4825072 | biostudies-literature