Cell-free lung model for mycobacterium abscessus 3D-biofilm formation

脓肿分枝杆菌是一种环境微生物，它在囊性纤维化(CF)肺中发现了一个致命的利基。感染脓肿支原体的成人和儿童都面临18个月的密集抗生素干预，包括静脉注射和雾化吸入，这会导致严重和创伤性的副作用。此外，治疗往往不成功，而且患者存在反复感染，这导致了与脓肿相关的高死亡率。此外，感染的发生率正在上升。细菌在肺环境中的持久性被认为是由于生物膜的形成，借助于典型的CF肺的厚厚的粘液基质。我们之前已经开发了一个2D体外肺模型，使我们能够评估雾化抗生素对脓肿支原体的疗效。除此之外，我们还发现了一些化合物，当它们与已知抗生素联合使用时，它们可以增强它们的抗菌效果。下一步，我们希望将这个模型进一步发展成基于3D水凝胶的系统，以确定在更具生理相关性的生物膜中的这种效果，就像在CF肺环境中观察到的那样。这将使我们更清楚地了解脓肿分枝杆菌在宿主肺内的生长和对抗生素应激的反应方式，并使我们能够进一步测试增强剂化合物在无细胞培养系统中的有效性。

Mycobacterium abscessus is an environmental microorganism that has found a deadly niche in the cystic fibrosis (CF) lung. Both adults and children infected with M. abscessus face 18 months of intensive antibiotic intervention, including both intravenous and nebulised formulations which result in severe and traumatic side effects. Furthermore, treatment is often unsuccessful, and patients present with recurrent infections that contribute to the high mortality rate associated with M. abscessus. Additionally, incidence of infections is rising. The bacterial persistence within the lung environment is thought to be attributed to biofilm formation, aided by the thick mucus matrix typical of the CF lung. We have previously developed a 2D in vitro lung model that enables us to assess the efficacy of nebulised antibiotics against M. abscessus. Beyond this, we have identified compounds that potentiate the antibacterial efficacy of known antibiotics when delivered in combination with them. As a next step, we would like to further develop this model into a 3D hydrogel-based system to determine this efficacy in a more physiologically relevant biofilm as would be observed in the CF lung environment. This will provide us with a much clearer understanding of the way in which M. abscessus grows and responds to antibiotic stress within the host lung, and will enable us to further test the efficacy of the potentiator compounds in a cell-free culture system.