Hopanoids as functional analogues of cholesterol in bacterial membranes

James P. Sáenz, Daniel Grosser, Alexander S. Bradley, Thibaut J. Lagny, Oksana Lavrynenko, Martyna Broda, Kai Simons

Research output: Contribution to journalArticlepeer-review

177 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)11971-11976
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume112
Issue number38
DOIs
StatePublished - Sep 22 2015

Keywords

  • Hopanoids
  • Membrane order
  • Methylobacterium
  • Multidrug efflux
  • Outer membrane

Fingerprint

Dive into the research topics of 'Hopanoids as functional analogues of cholesterol in bacterial membranes'. Together they form a unique fingerprint.

Cite this