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Bedaquiline Eliminates Bactericidal Activity of ?-Lactams against Mycobacterium abscessus.

ABSTRACT: 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.

SUBMITTER: Lindman M

PROVIDER: S-EPMC6658768 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Bedaquiline Eliminates Bactericidal Activity of β-Lactams against Mycobacterium abscessus.

Lindman Marissa M Dick Thomas T

Antimicrobial agents and chemotherapy 20190725 8

The β-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 β-lactams. Thus, the addition of bedaquiline to β-lactam-containing regimes may nega ...[more]

PMID: 31182531

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