Hopanoids as functional analogues of cholesterol in bacterial membranes

The functionality of cellular membranes relies on the molecular order imparted by lipids. In eukaryotes, sterols such as cholesterol modulate membrane order, yet they are not typically found in prokaryotes. The structurally similar bacterial hopanoids exhibit similar ordering properties as sterols i...

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Published in:Proceedings of the National Academy of Sciences - PNAS 2015-09, Vol.112 (38), p.11971-11976
Main Authors: Sáenz, James P., Grosser, Daniel, Bradley, Alexander S., Lagny, Thibaut J., Lavrynenko, Oksana, Broda, Martyna, Simons, Kai
Format: Article
Language:English
Subjects:
Bacteria
Biological Sciences
Biological Transport
Cell Membrane - metabolism
Cholesterol
Cholesterol - metabolism
Energy Metabolism
Lipid A - metabolism
Lipids
Lipids - chemistry
Membranes
Methylobacterium extorquens
Methylobacterium extorquens - metabolism
Organic chemistry
Phospholipids - chemistry
Phospholipids - metabolism
Prokaryotes
Triterpenes - chemistry
Triterpenes - metabolism
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Summary:The functionality of cellular membranes relies on the molecular order imparted by lipids. In eukaryotes, sterols such as cholesterol modulate membrane order, yet they are not typically found in prokaryotes. The structurally similar bacterial hopanoids exhibit similar ordering properties as sterols in vitro, but their exact physiological role in living bacteria is relatively uncharted. We present evidence that hopanoids interact with glycolipids in bacterial outer membranes to form a highly ordered bilayer in a manner analogous to the interaction of sterols with sphingolipids in eukaryotic plasma membranes. Furthermore, multidrug transport is impaired in a hopanoid-deficient mutant of the gram-negativeMethylobacterium extorquens, which introduces a link between membrane order and an energy-dependent, membrane-associated function in prokaryotes. Thus, we reveal a convergence in the architecture of bacterial and eukaryotic membranes and implicate the biosynthetic pathways of hopanoids and other order-modulating lipids as potential targets to fight pathogenic multidrug resistance.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1515607112