Whole genome sequencing of large colony and small colony variant sub populations from drug exposed Mycobacterium tuberculosis mshD mutant
Mycothiol acetyltransferase MshD is critical for mycothiol biosynthesis and redox homeostasis in Mycobacterium tuberculosis. Loss of function mutation of mshD generates pronounced phenotypic heterogeneity, producing co existing large colony (LC) and small colony variant (SCV) subpopulations under antibiotic stress. To investigate whether this colony dimorphism arises from stable, shared genetic alterations, we performed whole genome re sequencing on LC and SCV sub colonies isolated from mshD populations exposed to isoniazid (INH), ethambutol (EMB), or clofazimine (CFZ). The un passaged parental mshD strain was included as internal reference control for variant calling. Genomic DNA was extracted from individually picked single colonies.