Secondary Metabolites from a New Antibiotic-Producing Endophytic Streptomyces Isolate Inhibited Pathogenic and Multidrug-Resistant Mycobacterium tuberculosis Strains

The long regimen of drug therapy, the emergence of drug-resistance (DR), and infections with non-tuberculous mycobacteria (NTMs) are alarming challenges in controlling tuberculosis (TB), a disease caused by <i>Mycobacterium tuberculosis</i> (<i>M.tb</i>), necessitating the pursuit of new, broad-spectrum anti-mycobacterials. With more than two-thirds of the clinically useful antibiotics originating from the bacterial phylum Actinomycetota, and their enormous diversity in India, we explored atypical environments for new bacterial strains with potential anti-<i>M.tb</i> activity. In this study, we the examined the secondary metabolites of soil and endophytic bacterial isolates from the wetland niches of Manipur, India, and determined their anti-mycobacterial properties using viability assays. The ethyl acetate culture filtrate extracts of one of the isolates, named <i>Streptomyces</i> sp. SbAr007, showed broad-spectrum anti-mycobacterial activity against laboratory <i>M.tb</i> strains H37Ra and H37Rv, a clinical drug-resistant <i>M.tb</i> and non-tuberculous mycobacteria (NTM). The isolate was characterized for its phenotype and genetic identity, which indicated its closeness to <i>Streptomyces samsunensis</i>, <i>Streptomyces malaysiensis</i>, and <i>Streptomyces solisilvae</i>. Further, macrophage infection assays showed that the extracts could effectively control the intracellular mycobacterial growth but had negligible cytotoxicity to PBMCs from healthy donors. LC-MS identified an unusual combination of antibiotics in these culture filtrate extracts, which can be further explored for specific active molecules or as a formulation against DR-TB.