Microbiome and Resistome of Mycobacterium ulcerans lesions

溃疡分枝杆菌病变的微生物组和耐药组

• 批准号: 461611374
• 负责人: Dr. Denise Dekker
• 金额: --
• 依托单位: Department of Medicine
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/461611374?language=en
• 关键词: Microbiome; Resistome; Mycobacterium; ulcerans; lesions

Buruli ulcer (BU) is a neglected bacterial disease, predominantly occurring in West Africa. The causative agent Mycobacterium ulcerans induces severe ulcerative skin lesions mainly in young children. The treatment of choice is an antibiotic combination therapy of rifampicin and clarithromycin supported by surgical debridement. Treatment success depends on several factors comprising the size of the affected skin, the composition of the bacterial wound flora, and also treatment compliance. However, despite successes of antibiotic therapy, a significant proportion of patients do not respond adequately to treatment, and wound healing varies substantially. In a considerable number of cases, therapy is delayed or has failed completely. Except from possible poor patient compliance, the bacterial composition of BU lesions might be a driving factor affecting the healing process, as well as antimicrobial resistance of bacteria within the wounds including those of M. ulcerans. These factors have so far received little attention in endemic areas in the most affected countries. Therefore, this project aims to analyse the wound microbiome of BU lesions by culture-based methods in addition to next generation sequencing analysis (NGS), where metagenomic analyses will complement the investigations to uncover the full range of bacterial diversity. BU patients will be enrolled in seven hospitals of Kumasi, Ghana, and surrounding cities. Samples will be collected from patients up to 9 months if the wounds do not heal. The proposed study will allow identification of relevant bacteria involved in the development of BU lesion, and their healing processes. NGS screens may also identify bacteria that cannot be cultured by standard methods, and have previously not been associated with delayed wound healing. In addition, sequencing based antibiotic resistance tests will be supported by phenotypic resistance screens. The bacterial composition of BU wounds will be compared amongst patients where despite adequate antibiotic therapy poor healing of the lesions was observed, and those that responded well to therapy. Individuals with a long and poor healing history are at risk to be colonized by a peculiar microbial flora and/or carrying antibiotic resistant bacteria including M. ulcerans strains. Thus, preparedness for the emergence of resistant bacteria is necessary to respond adequately to changing therapy regimes.

布鲁里溃疡（BU）是一种被忽视的细菌性疾病，主要发生在西非。病原体溃疡分枝杆菌主要在幼儿中引起严重的溃疡性皮肤病变。治疗的选择是利福平和克拉霉素的抗生素联合治疗，辅以手术清创。治疗成功取决于几个因素，包括受影响皮肤的大小、细菌伤口植物群的组成以及治疗依从性。然而，尽管抗生素治疗取得了成功，但很大一部分患者对治疗反应不充分，伤口愈合差异很大。在相当多的情况下，治疗被延迟或完全失败。除了可能的患者依从性差外，BU病变的细菌组成可能是影响愈合过程以及伤口内细菌（包括M.溃疡。迄今为止，在受影响最严重的国家的流行地区，这些因素很少受到注意。因此，该项目旨在通过基于培养的方法以及下一代测序分析（NGS）来分析BU病变的伤口微生物组，其中宏基因组分析将补充调查，以揭示细菌多样性的全部范围。BU患者将在加纳库马西及周边城市的7家医院入组。如果伤口未愈合，将从9个月内的患者中采集样本。拟议的研究将允许识别参与BU病变发展及其愈合过程的相关细菌。NGS筛选还可以识别无法通过标准方法培养的细菌，并且以前与延迟伤口愈合无关。此外，基于测序的抗生素耐药性试验将得到表型耐药性筛选的支持。将在尽管进行了充分的抗生素治疗但观察到病变愈合不良的患者与对治疗反应良好的患者之间比较BU伤口的细菌组成。具有长期和不良愈合史的个体处于被特殊微生物植物群定殖和/或携带抗生素抗性细菌（包括M.溃疡菌株。因此，有必要为耐药菌的出现做好准备，以充分应对不断变化的治疗方案。