Investigating multi-drug resistant tuberculosis in the 3-dimensional bioelectrospray cell culture model

结核病是一种细菌性疾病，曾经导致该国三分之一的死亡，现在正变得越来越难以治疗。事实上，一些菌株现在对以前用于治疗结核病感染的所有抗生素都具有完全的耐药性。确定新的抗生素治疗方法的困难之一是缺乏良好的系统来研究当细菌进入人体细胞时抗生素是如何起作用的。我们已经开发了一种研究结核病和人类血细胞的新方法，通过制造同时浸渍细胞和结核菌的微小液滴。我们将使用这个系统来研究当细菌被感染到人体细胞中时，普通结核病和耐药结核病是如何被抗生素杀死的。我们的实验表明，我们所知道的对结核病患者有效的抗生素在我们的新系统中也有效，但在标准感染系统中不起作用，因此这种方法提供了一种识别抗生素的新方法，这是传统方法所无法发现的。一旦我们进一步开发了模型，我们将研究飞沫中标准的和新发现的抗生素。然后，我们将在模型中添加第二级，使细胞缺氧和营养，以更准确地反映结核病患者的情况。我们将研究这种压力是如何改变细菌和人类细胞的行为的。然后，我们可以将该系统与现代流体系统相结合，以筛选大量的新治疗方法。此外，一旦该系统被开发出来，我们将能够利用它来调查其他细菌感染，这些细菌感染对抗生素的耐药性也越来越强。因此，这是一个具有广泛潜力的系统，可用于解决现代时代的主要医学挑战之一。

Tuberculosis is a bacterial disease that used to cause one third of all deaths in this country and is now is becoming progressively more difficult to treat. Indeed, some strains are now completely resistant to all antibiotics previously used to cure tuberculosis infection. One of the difficulties in identifying new antibiotic treatments is the lack of good systems to study how antibiotics work when the bacteria are inside human cells. We have developed a new way of studying tuberculosis and human blood cells by making tiny droplets that are impregnated with both cells and tuberculosis bugs. We will use this system to study how normal tuberculosis and drug-resistant tuberculosis are killed by antibiotics when the bacteria are infected into human cells. We have experiments showing that antibiotics that we know work in patients with tuberculosis also work in our new system but do not work in standard infection systems, and so this approach provides a new way of identifying antibiotics that will not be found by more traditional approaches.Once we have developed the model further, we will investigate standard and newly discovered antibiotics in the droplets. We will then add a second level to the model, starving the cells of oxygen and nutrients to reflect conditions in patients with tuberculosis more accurately. We will study how this stress changes the behaviour of both the bacteria and the human cells. We can then integrate this system with modern fluidic systems to screen a large array of new treatments. Furthermore, once the system has been developed, we will be able to use this to investigate other bacterial infections which are also becoming more resistant to antibiotics. Therefore, this is a system of broad potential that can be used to address one of the major medical challenges of the modern era.