Un-ravelling the network of regulation of multidrug resistance in Salmonella enterica

每年人们都会接触到非伤寒沙门氏菌，通常来自受污染的食品。有些人死于感染而生病。这对老年人和年轻人来说尤其危险，这些人通常需要抗生素治疗。不幸的是，沙门氏菌的抗生素耐药性并不罕见。在这个项目中，我们将进行实验，使我们能够了解多种抗生素（药物）耐药性（MDR）是如何引起的。我们将识别控制AcrAB-TolC系统产生的基因和/或蛋白质，该系统从细菌细胞输出抗生素，从而使其继续生长并引起感染。如果这个系统失活，细菌就会对抗生素非常敏感，很难在宿主（例如家禽）上定植，而且很难选择耐抗生素沙门氏菌。我们预计我们将发现赋予耐多药的蛋白质，这些蛋白质也可以用作抑制AcrAB-TolC产生的药物的靶标。这些新药将使沙门氏菌难以引起感染并产生抗生素耐药性。

Every year people are exposed to non-typhoidal salmonella bacteria, typically from contaminated foodstuffs. Some people succumb to infection and get ill. This is particularly dangerous for the very old and young, and these people often need treatment with antibiotics. Unfortunately, antibiotic resistance in salmonella is not uncommon. In this project we will perform experiments that will allow us to understand how multiple antibiotic (drug) resistance (MDR) is caused. We will identify genes and/or the proteins that control the production of the AcrAB-TolC system, which exports antibiotics from the bacterial cell and so allows it to continue to grow and cause infection. If this system is inactivated the bacterium becomes very susceptible to antibiotics, finds it difficult to colonise the host (e.g. poultry) and antibiotic resistant salmonella are hard to select. We anticipate that we will find proteins that confer MDR and that can also be used as targets for drugs that will inhibit production of AcrAB-TolC. Such new drugs would make it difficult for the salmonella to cause infection and be antibiotic resistant.