Validation of inhibitors of an ABC transporter required to transport lipopolysaccharide to the cell surface in Escherichia coli |
| |
Authors: | David J. Sherman Suguru Okuda William A. Denny Daniel Kahne |
| |
Affiliation: | 1. Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Str., Cambridge, MA 02138, United States;2. Auckland Cancer Society Research Centre, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1020, New Zealand;3. Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 45 Shattuck Str., Boston, MA 02115, United States;1. University of Oxford, Dept. of Chemistry, Mansfield Road, Oxford, OX1 3TA, UK |
| |
Abstract: | The presence of lipopolysaccharide (LPS) in the outer leaflet of the outer membrane (OM) of Gram-negative bacteria creates a permeability barrier that prevents the entry of most currently available antibiotics. The seven lipopolysaccharide transport (Lpt) proteins involved in transporting and assembling this glycolipid are essential for growth and division in Escherichia coli; therefore, inhibiting their functions leads to cell death. LptB, the ATPase that provides energy for LPS transport and assembly, forms a complex with three other inner membrane (IM) components, LptC, F, and G. We demonstrate that inhibitors of pure LptB can also inhibit the full IM complex, LptBFGC, purified in detergent. We also compare inhibition of LptB and the LptBFGC complex with the antibiotic activity of these compounds. Our long-term goal is to develop tools to study inhibitors of LPS biogenesis that could serve as potentiators by disrupting the OM permeability barrier, facilitating entry of clinically used antibiotics not normally used to treat Gram-negative infections, or that can serve as antibiotics themselves. |
| |
Keywords: | Gram-negative Lipopolysaccharide Antibiotics ABC transporter |
本文献已被 ScienceDirect 等数据库收录! |
|