Author:
Sullivan Mark R.,McGowen Kerry,Liu Qiang,Akusobi Chidiebere,Young David C.,Mayfield Jacob A.,Raman Sahadevan,Wolf Ian D.,Moody D. Branch,Aldrich Courtney C.,Muir Alexander,Rubin Eric J.
Abstract
AbstractMycobacterium abscessus is an emerging pathogen resistant to most frontline antibiotics. M. abscessus causes lung infection, predominantly in patients with lung disease or structural abnormalities. To interrogate mechanisms required for M. abscessus survival in the lung, we developed a lung infection model using air-liquid interface culture and performed a screen to identify differentially required genes. In the lung model, synthesis of the cofactor biotin is required due to increased intracellular biotin demand, and pharmacological inhibition of biotin synthesis halts M. abscessus proliferation. Increased quantities of biotin are required to sustain fatty acid remodeling that serves to increase cell envelope fluidity, which in turn promotes M. abscessus survival in the alkaline lung environment. Together, these results indicate that biotin-dependent fatty acid remodeling plays a critical role in pathogenic adaptation to the lung niche and suggests that biotin synthesis and fatty acid metabolism are therapeutic targets for treatment of M. abscessus infection.
Publisher
Cold Spring Harbor Laboratory
Cited by
2 articles.
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