Genetic adaptation of non-typhoid Salmonella within human and animal reservoirs in sub-Sahara Africa

肠道沙门氏菌每年在全世界造成120多万人死亡，其中大多数发生在资源贫乏的国家。伤寒以外的沙门氏菌感染，即所谓的非伤寒沙门氏菌（NTS），在工业化国家通常仅限于胃肠道疾病。相比之下，在撒哈拉以南非洲（SSA），NTS是成人和儿童细菌性血流感染的最常见原因。而在工业化国家，NTS感染通常是人畜共患的，这不能证实NTS是来自SSA的，这表明人畜共患传播是主要的传播途径。人类入侵沙门氏菌的全基因组测序（WGS）数据强烈表明，沙门氏菌基因组已经进化和适应特定的主机支持的假设，可能的人传人最近进化的非洲NTS菌株。到目前为止，人类和人畜共患沙门氏菌分离SSA的基因组比较尚未进行。有一个重要的信息差距，迫切需要填补，以了解感染水库，沙门氏菌宿主适应和传播途径，以制定有效的管理和控制战略。本研究旨在通过全基因组测序鉴定患病和健康儿童以及家畜中的沙门氏菌，以确定沙门氏菌对宿主的传播宿主和适应性。此外，还应对感染侵袭性沙门氏菌的儿童及其父母进行外显子组分析，以检测有助于识别相关代谢途径的风险变体。总体目标如下：·确定动物和人类来源的NTS的频率;·使用全基因组测序检测所收集沙门氏菌分离株的基因组差异;·检测宿主对侵袭性沙门氏菌疾病的遗传易感性;·确定iNTS和肠道NTS感染（eNTS）的社会经济后果;·加强非洲和非洲-德国合作伙伴的科学网络，支持非洲科学家的职业发展，包括南北和南南人员交流。

Salmonella enterica causes more than 1.2 million annual deaths worldwide, the majority occurring in resource-poor countries. Salmonella infections other than Typhoid fever, so-called non-typhoid Salmonella (NTS), are usually limited to gastrointestinal disease in industrialized countries. In contrast, in sub-Sahara Africa (SSA), NTS are the most frequent cause of bacterial bloodstream infections in both adults and children. While in industrialized countries, infections with NTS are typically of zoonotic origin this coudl not be confirmed for NTS starisn from SSA suggesting anthroponotic transmission as the major transmission route. Whole genome sequencing (WGS) data of human invasive Salmonella strongly suggests that the Salmonella genome has evolved and adapted within specific hosts supporting the hypothesis of possible anthroponotic transmission of the recently evolved African NTS strains. So far, genome comparisons of human and zoonotic Salmonella isolates from SSA have not been conducted. There is an important information gap, which urgently needs to be filled to understand infection reservoirs, Salmonella host adaptation and transmission pathways in order to devise effective management and control strategies. This study aims to identify Samonella enterica in sick and healthy children and in livestock animals to identify tranmssion reservoirs and adaptation of Salmonella to the host by whole genome sequencing. In addition an Exome anylsis shall be performed from children with invasive salmonelloses and their parents in order to detect risk variants that will help to identify relevant metabolic pathways.The overall objectives are as follows:•to determine the frequency of NTS from animal and human sources;•to detect differences in the genomes of the collected Salmonella isolates using whole genome sequencing;•to detect host genetic susceptibility to invasive Salmonella disease;•to determine socio-economic consequences of iNTS and enteric NTS infections (eNTS);•to strengthen the scientific network within the African- and African-German partners and support professional career development of African scientists including North-South and South-South exchange of personnel.