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

在三维生物电喷雾细胞培养模型中研究多重耐药结核病

• 批准号: MR/N006631/1
• 负责人: Paul Elkington
• 金额: $ 30.83万
• 依托单位: University of Southampton
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2015
• 资助国家: 英国
• 起止时间: 2015 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FN006631%2F1
• 关键词: Investigating; multi; drug; resistant; tuberculosis

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.

结核病是一种细菌性疾病，过去在这个国家造成三分之一的死亡，现在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完全耐药。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在人体细胞内时抗生素是如何工作的。我们已经开发出一种研究结核病和人类血细胞的新方法，通过制造充满细胞和结核病菌的微小液滴。我们将利用这个系统来研究当细菌感染到人体细胞中时，正常的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，我们知道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无效，因此这种方法提供了一种新的方法来识别传统方法无法发现的抗生素。一旦我们进一步开发了该模型，我们将研究液滴中的标准和新发现的抗生素。然后，我们将在模型中添加第二个层次，使细胞缺乏氧气和营养，以更准确地反映结核病患者的状况。我们将研究这种压力如何改变细菌和人体细胞的行为。然后，我们可以将该系统与现代流体系统集成，以筛选大量新的治疗方法。此外，一旦该系统被开发出来，我们将能够利用它来研究其他对抗生素耐药性越来越强的细菌感染。因此，这是一个具有广泛潜力的系统，可用于解决现代医学的主要挑战之一。

项目成果

A Bioengineered Three-Dimensional Cell Culture Platform Integrated with Microfluidics To Address Antimicrobial Resistance in Tuberculosis.

• DOI: 10.1128/mbio.02073-16
• 发表时间: 2017-02-07
• 期刊: mBio
• 影响因子: 6.4
• 作者: Bielecka MK;Tezera LB;Zmijan R;Drobniewski F;Zhang X;Jayasinghe S;Elkington P
• 通讯作者: Elkington P

Personal respirators for population level control of the COVID19 pandemic.

用于控制 COVID19 大流行的人口水平的个人呼吸器。

• DOI: 10.1016/j.jinf.2020.04.025
• 发表时间: 2020
• 期刊: The Journal of infection
• 作者: Elkington P

Tuberculosis: An Infection-Initiated Autoimmune Disease?

• DOI: 10.1016/j.it.2016.09.007
• 发表时间: 2016-12
• 期刊: Trends in immunology
• 影响因子: 16.8
• 作者: Elkington P;Tebruegge M;Mansour S
• 通讯作者: Mansour S

Mycobacterium tuberculosis subverts negative regulatory pathways in human macrophages to drive immunopathology.

• DOI: 10.1371/journal.ppat.1006367
• 发表时间: 2017-06
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Brace PT;Tezera LB;Bielecka MK;Mellows T;Garay D;Tian S;Rand L;Green J;Jogai S;Steele AJ;Millar TM;Sanchez-Elsner T;Friedland JS;Proud CG;Elkington PT
• 通讯作者: Elkington PT

Anti-Tuberculosis Activity of Three Carbapenems, Clofazimine and Nitazoxanide Using a Novel Ex Vivo Phenotypic Drug Susceptibility Model of Human Tuberculosis.

• DOI: 10.3390/antibiotics11101274
• 发表时间: 2022-09-20
• 期刊: Antibiotics (Basel, Switzerland)