Outer membrane permeability and antibiotic resistance

Biochim Biophys Acta. 2009 May;1794(5):808-16. doi: 10.1016/j.bbapap.2008.11.005. Epub 2008 Nov 27.


To date most antibiotics are targeted at intracellular processes, and must be able to penetrate the bacterial cell envelope. In particular, the outer membrane of gram-negative bacteria provides a formidable barrier that must be overcome. There are essentially two pathways that antibiotics can take through the outer membrane: a lipid-mediated pathway for hydrophobic antibiotics, and general diffusion porins for hydrophilic antibiotics. The lipid and protein compositions of the outer membrane have a strong impact on the sensitivity of bacteria to many types of antibiotics, and drug resistance involving modifications of these macromolecules is common. This review will describe the molecular mechanisms for permeation of antibiotics through the outer membrane, and the strategies that bacteria have deployed to resist antibiotics by modifications of these pathways.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Bacterial Agents / metabolism
  • Bacterial Outer Membrane Proteins / metabolism*
  • Cell Membrane Permeability / genetics
  • Cell Membrane Permeability / physiology*
  • Drug Resistance, Microbial / genetics*
  • Gram-Negative Bacteria / genetics*
  • Gram-Negative Bacteria / metabolism
  • Lipopolysaccharides / physiology
  • Porins / chemistry
  • Porins / metabolism


  • Anti-Bacterial Agents
  • Bacterial Outer Membrane Proteins
  • Kdo2-lipid A
  • Lipopolysaccharides
  • OmpF protein
  • Porins