Spatially distinct and metabolically active membrane domain in mycobacteria

Protected from host immune attack and antibiotic penetration by their unique cell envelope, mycobacterial pathogens cause devastating human diseases such as tuberculosis. Seamless coordination of cell growth with cell envelope elongation at the pole maintains this barrier. Unraveling this spatiotemp...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2016-05, Vol.113 (19), p.5400-5405
Main Authors: Hayashi, Jennifer M., Luo, Chu-Yuan, Mayfield, Jacob A., Hsu, Tsungda, Fukuda, Takeshi, Walfield, Andrew L., Giffen, Samantha R., Leszyk, John D., Baer, Christina E., Bennion, Owen T., Madduri, Ashoka, Shaffer, Scott A., Aldridge, Bree B., Sassetti, Christopher M., Sandler, Steven J., Kinoshita, Taroh, Moody, D. Branch, Morita, Yasu S.
Format: Article
Language:English
Subjects:
Bacteria
Bacterial Proteins - metabolism
Biological Sciences
Lipid Metabolism - physiology
Membrane Microdomains - metabolism
Membrane Microdomains - ultrastructure
Membrane Proteins - metabolism
Membranes
Metabolism
Mycobacterium - metabolism
Mycobacterium - ultrastructure
Mycobacterium smegmatis
Pathogens
Proteomics
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Summary:Protected from host immune attack and antibiotic penetration by their unique cell envelope, mycobacterial pathogens cause devastating human diseases such as tuberculosis. Seamless coordination of cell growth with cell envelope elongation at the pole maintains this barrier. Unraveling this spatiotemporal regulation is a potential strategy for controlling mycobacterial infections. Our biochemical analysis previously revealed two functionally distinct membrane fractions in Mycobacterium smegmatis cell lysates: plasma membrane tightly associated with the cell wall (PM-CW) and a distinct fraction of pure membrane free of cell wall components (PMf). To provide further insight into the functions of these membrane fractions, we took the approach of comparative proteomics and identified more than 300 proteins specifically associated with the PMf, including essential enzymes involved in cell envelope synthesis such as a mannosyltransferase, Ppm1, and a galactosyltransferase, GlfT2. Furthermore, comparative lipidomics revealed the distinct lipid composition of the PMf, with specific association of key cell envelope biosynthetic precursors. Live-imaging fluorescence microscopy visualized the PMf as patches of membrane spatially distinct from the PM-CW and notably enriched in the pole of the growing cells. Taken together, our study provides the basis for assigning the PMf as a spatiotemporally distinct and metabolically active membrane domain involved in cell envelope biogenesis.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1525165113