LAUSR

Significance Cholesterol catabolism, a potential therapeutic target in Mycobacterium tuberculosis, remains underexplored in nontuberculosis mycobacteria. Our study revealed that the opportunistic pathogen Mycobacterium abscessus contains catabolic pathways for cholesterol and 4-androstenedione, and that among strains of the M. abscessus complex, the two pathways converge at a point that is unique among steroid-degrading bacteria. Consistent with it being the enzyme at the point of convergence, HsaD efficiently transformed substrates from both pathways. A ΔhsaD mutant of M. abscessus did not grow in macrophages, indicating that cholesterol is a growth substrate for intracellular bacteria. The mutant also showed steroid-dependent toxicity. This study provides insight into the bacterial catabolism of steroids and the nutritional requirements of intracellular M. abscessus.