Prevention and Restriction of Antimicrobial Resistance in Pneumococci by Multi-Level Modelling

肺炎链球菌是工业化国家和发展中国家的主要健康威胁。这种病原体既影响年轻人，也影响老年人，免疫能力强的人以及免疫功能低下的人。通过在不同种群中的基因重组，单个菌株不仅能够逃避疫苗接种，而且能够获得抗菌素耐药性(AMR)，然后可以传播。本研究旨在了解这种肺炎链球菌AMR谱系在遗传、细菌、宿主和种群水平上的机制和分布，为AMR的风险评估、预防和减少制定新的策略。特别是，抗性产生和选择的环境、免疫学和药理学驱动因素、遗传种群动态以及新性状在不同寄主条件下的适合性将被分析和建模。为此，一个具有互补专业知识的多国研究人员联盟已经成立。该联盟可获得的是临床上重要的和新出现的肺炎球菌AMR菌株，以及来自临床队列的相关患者元数据(临床、遗传和转录)，以及来自泰国队列的高度详细的携带样本。该联盟的成员在微生物学、细菌遗传学、生物信息学、体内/体外模型方面拥有公认的专业知识，而其他成员则是治疗儿科和成人肺炎球菌感染的临床专家。该联盟将通过对耐药性的出现、选择和在不同环境中的传播进行多层次建模，共同努力制定应对主要健康威胁的抗菌素耐药性的对策。

Streptococcus pneumoniae is a major health threat in industrialized and developing countries. The pathogen affects both young and old people, immune-competent as well as immunocompromised individuals. By genetic recombination within diverse populations, individual strains are not only able to evade vaccination but also able to acquire antimicrobial resistance (AMR), which can then be transmitted onwards.This proposal aims to understand the mechanisms and distribution of this pneumococcal AMR repertoire at the genetic, bacterial, host and population levels to layout new strategies for risk assessment, prevention and reduction of AMR. In particular, the environmental, immunological and pharmacological drivers of resistance emergence and selection, the genetic population dynamics, as well as the fitness of the new traits in different host conditions will be analysed and modelled.To this end, a multinational consortium of researchers with complementary expertise has been formed. Available to the consortium are clinically important and newly emerged pneumococcal AMR strains, together with related patient metadata (clinical, genetic and transcriptomic) from clinical cohorts as well as highly detailed carriage sampling from a Thai cohort. Consortium members have proven expertise in microbiology, bacterial genetics, bioinformatics, in vivo/in vitro models while others are clinicians expert in the treatment of pneumococcal infections in both paediatric and adult patients.In a concerted effort, this consortium will develop countermeasures against antimicrobial resistance in a major health threat by multi-level modelling of its resistance emergence, selection, and transmission in diverse environments.