TY - JOUR
T1 - Hopanoids as functional analogues of cholesterol in bacterial membranes
AU - Sáenz, James P.
AU - Grosser, Daniel
AU - Bradley, Alexander S.
AU - Lagny, Thibaut J.
AU - Lavrynenko, Oksana
AU - Broda, Martyna
AU - Simons, Kai
PY - 2015/9/22
Y1 - 2015/9/22
N2 - 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.
AB - 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.
KW - Hopanoids
KW - Membrane order
KW - Methylobacterium
KW - Multidrug efflux
KW - Outer membrane
UR - http://www.scopus.com/inward/record.url?scp=84942908911&partnerID=8YFLogxK
U2 - 10.1073/pnas.1515607112
DO - 10.1073/pnas.1515607112
M3 - Article
C2 - 26351677
AN - SCOPUS:84942908911
SN - 0027-8424
VL - 112
SP - 11971
EP - 11976
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 38
ER -