Structure and mechanism of the Mla lipid transport system in the multidrug-resistant bacterium A. baumannii

点击翻译按钮获取中文摘要

In recent years, we have observed a dramatic increase in "superbugs", bacteria that are resistant to all known antibiotics. This is a particularly important worry in hospital settings, where superbugs cause untreatable infections in patients undergoing routine medical procedures. More than 20,000 people die from superbug infections every year.In many bacteria, this drug resistance is caused by a thick lipid later (the outer membrane) on their surface. This membrane acts as a physical barrier, preventing many drugs from entering the bacterial cell. The lipid composition of this outer membrane is very specifically regulated, as it is critical for its physical integrity. However, the mechanisms used by bacteria to transport lipids to and from the outer membrane are still poorly understood.Recently, a set of proteins termed the Mla system (for Maintenance of Lipid Asymmetry) was shown to be essential to maintain an intact outer membrane. The aim of this project is to characterize the molecular basis for lipid transport by this system. Specifically, we will study the Mla system from the bacterium Acinetobacter baumannii, a known multi-drug resistant bacterium responsible for up to 20% of antibiotic-resistant infections world-wide.We will study how the different Mla proteins interact with each other, and how they recruit and transport lipids. In particular, we will exploit the latest advances in high-resolution electron microscopy to characterize these proteins at the atomic level.This will allow us to understand how the proteins from the Mla system recognize lipids and transport them to and/or from the outer membrane. Ultimately, this could be exploited for the development of therapeutics that prevent antibiotics resistance.