| 备 注:
Prof. Dr. Mathias Winterhalter, Professor of Biophysics (Focus Area: Health - Life Sciences & Chemistry, Jacobs University Bremen gGmbH)
Gram-negative bacteria are surrounded by a cellular envelope that comprises outer and inner membranes with distinct properties and provides a potent physical barrier to antibacterial agents. The discovery of new agents to treat drug-resistant Gram- negative infections generally relies on the agent’s ability to penetrate at one or both envelope membranes. Furthermore, even if an agent penetrates these membranes it can be rapidly transported out of the cell by numerous broadly acting efflux pumps, rendering the agent ineffective. The combination of this intrinsic dual-penetration barrier with the potential for rapid efflux often leads to situations in which compounds with intrinsic activity against intracellular or periplasmic targets display poor antibacterial activity. At present, there are no reliable methods for measuring these penetration and efflux processes in Gram-negative bacteria, a bottleneck that substantially hinders the ability of scientists to optimize antimicrobial activity in intact bacterial cells.