Unravelling the mechanisms of the biogenesis of the outer membrane of Gram-negative bacteria: a step toward the development of new antibiotics

The outer membrane of Gram negative bacteria such as Escherichia coli is a permeability barrier that is essential for the viability of Gram-negative bacteria and protects them against antimicrobial drugs, including hydrophobic antibiotics. Outer membrane components, including phospholipids, lipopolysaccharids and proteins are synthesized in the cytoplasm and the cytoplasmic membrane. The mechanisms by which unfolded proteins and lipids are then transported through the hydrophilic periplasm and are inserted in the outer membrane are essentially unknown. Our overall goal is to solve the fascinating problem of how such a complex macromolecular structure is assembled in a compartment devoid of obvious energy sources. Moreover, the proteins that are involved in OM biogenesis are also attractive targets for the design of new antibiotics and anti-inflammatory drugs. Developing new antibiotics active against E. coli and other Gram negative bacteria is criticial because the number of E. coli strains that are resistant to antibiotics is rapidly rising. We will describe results obtained recently in our laboratory that allowed us to characterize several periplasmic chaperones involved in the folding of envelope proteins