High-throughput cytological profiling uncovers genotype-phenotype associations in <i>Mycobacterium tuberculosis</i> clinical isolates.

ABSTRACT: Understanding the functional impact of bacterial genetic diversity is crucial for linking pathogen variants to clinical outcomes. Here, we introduce a high-throughput cytological profiling pipeline optimized for Mycobacterium tuberculosis (Mtb) clinical strains, integrating OD-calibrated feature analysis and high-content microscopy. Our system quantifies single-bacterium morphological and physiological traits related to DNA replication, redox state, carbon metabolism, and cell envelope dynamics. Applied to 64 Mtb clinical isolates from lineages 1, 2, and 4, the approach revealed that cytological phenotypes recapitulate genetic relationships and exhibit both lineage- and density-dependent dynamics. Notably, we identified a link between a convergent "small cell" phenotype and a conver

SUBMITTER: Liu Q 

PROVIDER: S-EPMC12625746 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature