Rv3723/LucA coordinates fatty acid and cholesterol uptake in Mycobacterium tuberculosis

Pathogenic bacteria have evolved highly specialized systems to extract essential nutrients from their hosts. Mycobacterium tuberculosis (Mtb) scavenges lipids (cholesterol and fatty acids) to maintain infections in mammals but mechanisms and proteins responsible for the import of fatty acids in Mtb...

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Veröffentlicht in:eLife Jg. 6
Hauptverfasser: Nazarova, Evgeniya V, Montague, Christine R, La, Thuy, Wilburn, Kaley M, Sukumar, Neelima, Lee, Wonsik, Caldwell, Shannon, Russell, David G, VanderVen, Brian C
Format: Journal Article
Sprache:Englisch
Veröffentlicht: England eLife Science Publications, Ltd 27.06.2017
eLife Sciences Publications Ltd
eLife Sciences Publications, Ltd
Schlagworte:
Animals
Bacteria
Bacterial Proteins - genetics
Bacterial Proteins - metabolism
Biological Transport
Carbon
Cells, Cultured
Cholesterol
Cholesterol - metabolism
Fatty acids
Fatty Acids - metabolism
Genomes
Health aspects
Infections
Laboratories
Lipids
Lungs
macrophages
Macrophages - microbiology
Membrane Transport Proteins - genetics
Membrane Transport Proteins - metabolism
Metabolism
Mice, Inbred BALB C
Microbiology and Infectious Disease
Mutagenesis, Insertional
mycobacterium
Mycobacterium tuberculosis
Mycobacterium tuberculosis - growth & development
Mycobacterium tuberculosis - metabolism
Nutrients
Observations
pathogenesis
Physiological aspects
Proteins
transport
Tuberculosis
Virulence
pathogenesis
macrophages
mycobacterium
fatty acids
infectious disease
microbiology
cholesterol
transport
ISSN:2050-084X, 2050-084X
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Zusammenfassung:Pathogenic bacteria have evolved highly specialized systems to extract essential nutrients from their hosts. Mycobacterium tuberculosis (Mtb) scavenges lipids (cholesterol and fatty acids) to maintain infections in mammals but mechanisms and proteins responsible for the import of fatty acids in Mtb were previously unknown. Here, we identify and determine that the previously uncharacterized protein Rv3723/LucA, functions to integrate cholesterol and fatty acid uptake in Mtb. Rv3723/LucA interacts with subunits of the Mce1 and Mce4 complexes to coordinate the activities of these nutrient transporters by maintaining their stability. We also demonstrate that Mce1 functions as a fatty acid transporter in Mtb and determine that facilitating cholesterol and fatty acid import via Rv3723/LucA is required for full bacterial virulence in vivo. These data establish that fatty acid and cholesterol assimilation are inexorably linked in Mtb and reveals a key function for Rv3723/LucA in in coordinating thetransport of both these substrates.
Bibliographie:ObjectType-Article-1
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ObjectType-Feature-2
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ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.26969