ADP-ribosylation-resistant rifabutin analogs show improved bactericidal activity against drug-tolerant in caseum surrogate.

Necrotic lesions and cavities filled with caseum are a hallmark of mycobacterial pulmonary disease. Bronchocavitary disease is associated with poor treatment outcomes. In caseum surrogate, entered an extended stationary phase showing tolerance to killing by most current antibiotics, suggesting that caseum persisters contribute to the poor performance of available treatments. Novel ADP-ribosylation-resistant rifabutin analogs exhibited bactericidal activity against these persisters at concentrations achievable by rifamycins in caseum.