Profiling the mycobacteria biofilm: a multidisciplinary mix of mutants and mass spectrometry

分枝杆菌生物膜分析：突变体和质谱的多学科组合

• 批准号: 2116954
• 金额: --
• 依托单位: University of Surrey
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2116954
• 关键词: Profiling; mycobacteria; biofilm; multidisciplinary; mix

Non-tuberculous mycobacteria (NTMs), such as Mycobacterium abscessus and chimaera, can cause high mortality and morbidity amongst patients who are immunocompromised or have chronic lung diseases, such as cystic fibrosis. Mycobacterial biofilms can form in the alveolar walls of such patients following inhalation from environmental reservoirs. Recently, pathogenic strains have been isolated from shower heads and hospital air conditioning units. Biofilms are notoriously difficult to eradicate and are associated with the development of increased antimicrobial resistance (AMR). Treatment for M. abscessus and chimaera infections often requires 2-3 antibiotics over 2 years.The question we want to address is whether the increased AMR and treatment time in NTM biofilm formation is due to lack of antibiotic penetration, resulting in non-therapeutic and AMR-generative levels, or the development of phenotypic and/or genetic resistance. In this project we will use Nano-SIMS (nano-scale secondary ion mass spectrometry) to measure penetration of the antibiotic bedaquiline (BDQ), used to treat NTM infections, into individual cells of NTM biofilms (M.abscessus and M.chimaera). Nano-SIMS maps the relative abundance of different ions down to the nano-scale and can be used to measure in profile through the biofilm. In addition, the minimum inhibitory concentration (MIC) and minimum duration for killing (MDK) of BDK will be measured to determine antibiotic susceptibility in biofilms and a planktonic growth control. Understanding the AMR generation and prolonged treatment in NTM biofilms could lead to improved mortality and morbidity. The development of novel treatment strategies could enhance treatment efficacy, reduce treatment duration and AMR development.

非结核分枝杆菌（NTM），如结核分枝杆菌和嵌合体，可导致免疫功能低下或患有慢性肺部疾病（如囊性纤维化）的患者的高死亡率和发病率。分枝杆菌生物膜可在此类患者从环境储库吸入后的肺泡壁中形成。最近，从淋浴喷头和医院空调机组中分离出致病菌株。众所周知，生物膜很难根除，并且与抗菌素耐药性（AMR）的增加有关。治疗M.我们想要解决的问题是，NTM生物膜形成中AMR和治疗时间的增加是否是由于缺乏抗生素渗透，导致非治疗性和AMR生成水平，或者表型和/或遗传抗性的发展。在这个项目中，我们将使用纳米SIMS（纳米级二次离子质谱法）来测量用于治疗NTM感染的抗生素贝达喹啉（BDQ）渗透到NTM生物膜的单个细胞中（M. dumessus和M.chimaera）。Nano-SIMS将不同离子的相对丰度映射到纳米尺度，并可用于测量生物膜的剖面。此外，还将测量BDK的最小抑菌浓度（MIC）和最短杀灭持续时间（MDK），以确定生物膜和促生长对照中的抗生素敏感性。了解AMR的产生和NTM生物膜中的长期治疗可能导致死亡率和发病率的改善。开发新的治疗策略可以提高治疗效果，缩短治疗时间和AMR发展。