Genomic approaches for detection and prevention of listeriosis outbreaks

李斯特氏菌是一种严重的食源性感染，是李斯特菌病的病原体。李斯特菌病的特点是住院率高，病死率高达30%，是食源性传染病中最高的。最近，对临床分离的金黄色葡萄球菌进行全基因组测序，提高了对李斯特菌病流行的认识和对其感染源的识别。根据获得的基因组数据，几乎三分之二的李斯特菌病病例发生在拥有100多个分离物的感染聚集区，其中一些分离物持续数年或数十年。在这些持久的李斯特菌病暴发期间，病原体的微进化将被用于经验性地确定变异性界限，以提高李斯特菌病暴发检测的可靠性，并确定使长期暴发成为可能的遗传决定因素。我们推测，杀菌剂的耐受性和作为生物膜的生长是LM在食品生产设施中的弹性以及长期暴发的表现的重要因素。这一假设将通过筛选已建立的LM模型人群的杀生剂耐受性来检验。随后的遗传关联研究将包括通过纳入可移动的遗传因素来改进目前应用的基于核心基因组的方法。该项目将改进目前李斯特菌病暴发检测的方法，同时获得有关杀菌剂耐药性的信息对预防暴发很重要。开发的工具和方法将很容易转移到其他细菌病原体。

The bacterium Listeria monocytogenes (LM) is the causative agent of listeriosis, a severe foodborne infection. Listeriosis is characterized by a high hospitalization rate and a fatality rate of up to 30%, the highest among foodborne infectious diseases. Whole genome sequencing of clinical LM isolates has recently improved recognition of epidemics of listeriosis and the identification of their infection sources. Based on the obtained genomic data almost 2/3 of all listeriosis cases occur in infection clusters with up to more than 100 isolates, some of them protracting over years or decades. Pathogen microevolution during these long-lasting listeriosis outbreaks will be used to empirically define variability cut-offs to increase the reliability of listeriosis outbreak detection and to identify genetic determinants that make long-lasting outbreaks possible. We hypothesize that biocide tolerance and growth as biofilm are important factors in the resilience of LM in food production facilities, and the manifestation of protracted outbreaks. This hypothesis will be tested by screening an established LM model population for biocide tolerance. The subsequent genetic association study will include the improvement of the currently applied core genome based methodology by the inclusion of mobile genetic elements. This project will improve the current methodology for listeriosis outbreak detection while the obtained information on biocide tolerance is important for outbreak prevention. The tools and methodologies developed will be easily transferable to other bacterial pathogens.