Bedaquiline Eliminates Bactericidal Activity of β-Lactams against Mycobacterium abscessus

The β-lactams imipenem and cefoxitin are used for the treatment of lung infections. Here, we show that these cell wall synthesis inhibitors trigger a lethal bacterial ATP burst by increasing oxidative phosphorylation. Cotreatment of with the antimycobacterial ATP synthase inhibitor bedaquiline suppr...

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Veröffentlicht in:Antimicrobial agents and chemotherapy 2019-08, Vol.63 (8)
Hauptverfasser: Lindman, Marissa, Dick, Thomas
Format: Artikel
Sprache:eng
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Zusammenfassung:The β-lactams imipenem and cefoxitin are used for the treatment of lung infections. Here, we show that these cell wall synthesis inhibitors trigger a lethal bacterial ATP burst by increasing oxidative phosphorylation. Cotreatment of 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 negatively affect treatment outcome.
ISSN:0066-4804
1098-6596
DOI:10.1128/AAC.00827-19