Bedaquiline eliminates bactericidal activity of -lactams against mycobacterium abscessus

The -lactams imipenem and cefoxitin are used for the treatment of Mycobacterium abscessus lung infections. Here, we show that these cell wall synthesis inhibitors trigger a lethal bacterial ATP burst by increasing oxidative phosphorylation. Cotreatment of M. abscessus with the antimycobacterial ATP synthase inhibitor bedaquiline suppresses this ATP burst and eliminates the bactericidal activity of -lactams. Thus, the addition of bedaquiline to -lactam-containing regimes may negatively affect treatment outcome.