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 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-negative Methylobacterium 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.
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany; saenz@mpi-cbg.de simons@mpi-cbg.de.
James P
JP
Sáenz
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany;
Daniel
D
Grosser
Department of Earth and Planetary Sciences, Washington University, St. Louis, MO 63130;
Alexander S
AS
Bradley
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany;
Thibaut J
TJ
Lagny
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany;
Oksana
O
Lavrynenko
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany; Department of Biotechnology, University of Wroclaw, 50-383 Wroclaw, Poland.
Martyna
M
Broda
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany; saenz@mpi-cbg.de simons@mpi-cbg.de.
Kai
K
Simons
D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism*; D004734:Energy Metabolism; D008050:Lipid A / Q000378:metabolism; D008055:Lipids / Q000737:chemistry*; D020601:Methylobacterium extorquens / Q000378:metabolism*; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D014315:Triterpenes / Q000737:chemistry / Q000378:metabolism
D008050:Lipid A; D008055:Lipids; D010743:Phospholipids; D014315:Triterpenes; C029766:diplopterol; D002784:Cholesterol
Methylobacterium; hopanoids; membrane order; multidrug efflux; outer membrane