The Role of the Outer Membrane of Gram-negative Bacteria in Antibiotic Resistance: Ajax’ Shield or Achilles’ Heel?

Abstract

There has been an enormous increase in our knowledge of the fundamental steps in the biosynthesis and assembly of the outer membrane of Gram-negative bacteria. Lipopolysaccharide is a major component of the outer membrane of Gram-negative bacteria as is peptidoglycan. Porins, efflux pumps and other transport proteins of the outer membrane are also present. It is clear that there are numerous essential proteins that have the potential to be targets for novel antimicrobial agents. Progress, however, has been slow. Much of the emphasis has been on cytoplasmic processes that were better understood earlier on, but have the drawback that two penetration barriers, with different permeability properties, have to be crossed. With the increased understanding of the late-stage events occurring in the periplasm, it may be possible to shift focus to these more accessible targets. Nevertheless, getting drugs across the outer membrane will remain a challenge to the ingenuity of the medicinal chemist.