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Altering lipid droplet homeostasis affects Coxiella burnetii intracellular growth

Minal Mulye, Brianne Zapata, View ORCID ProfileStacey Gilk
doi: https://doi.org/10.1101/112300
Minal Mulye
Indiana University School of Medicine
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Brianne Zapata
Indiana University School of Medicine
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Stacey Gilk
Indiana University School of Medicine
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Abstract

Coxiella burnetii is an obligate intracellular bacterial pathogen and a causative agent of culture-negative endocarditis. While C. burnetii initially infects alveolar macrophages, it has also been found in lipid droplet (LD)-containing foamy macrophages in the cardiac valves of endocarditis patients. In addition, transcriptional studies of C. burnetii-infected macrophages reported differential regulation of the LD coat protein-encoding gene perilipin 2 (plin-2). To further investigate the relationship between LDs and C. burnetii, we compared LD numbers using fluorescence microscopy in mock-infected and C. burnetii-infected alveolar macrophages. On average, C. burnetii-infected macrophages contained twice as many LDs as mock-infected macrophages. LD numbers increased as early as 24 hours post-infection, an effect reversed by blocking C. burnetii protein synthesis. The observed LD accumulation was dependent on the C. burnetii Type 4B Secretion System (T4BSS), a major virulence factor that manipulates host cellular processes by secreting bacterial effector proteins into the host cell cytoplasm. To determine the importance of LDs during C. burnetii infection, we manipulated LD homeostasis and assessed C. burnetii intracellular growth. Surprisingly, blocking LD formation with the pharmacological inhibitors triacsin C or T863, or knocking out acyl-CoA transferase-1 (acat-1) in alveolar macrophages, increased C. burnetii growth at least 2-fold. Conversely, preventing LD lipolysis by inhibiting adipose triglyceride lipase (ATGL) with atglistatin almost completely blocked bacterial growth, suggesting LD breakdown is essential for C. burnetii. Together these data suggest that maintenance of LD homeostasis, possibly via the C. burnetii T4BSS, is critical for bacterial growth.

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Posted October 02, 2017.
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Altering lipid droplet homeostasis affects Coxiella burnetii intracellular growth
Minal Mulye, Brianne Zapata, Stacey Gilk
bioRxiv 112300; doi: https://doi.org/10.1101/112300
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Altering lipid droplet homeostasis affects Coxiella burnetii intracellular growth
Minal Mulye, Brianne Zapata, Stacey Gilk
bioRxiv 112300; doi: https://doi.org/10.1101/112300

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