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

全球每年有120多万人死于肠道沙门氏菌，其中大部分发生在资源贫乏的国家。除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)，无论是成人还是儿童，NTS都是细菌血液感染的最常见原因。而在工业化国家，NTS的感染通常是人畜共患病，这不能从SSA确认NTS星状病毒，这表明人的传播是主要的传播途径。人类侵袭性沙门氏菌的全基因组测序(WGS)数据有力地表明，沙门氏菌基因组已在特定宿主内进化和适应，支持最近进化的非洲NTS毒株可能存在人为传播的假说。到目前为止，还没有对来自SSA的人与人畜共患沙门氏菌分离株进行基因组比较。有一个重要的信息空白，迫切需要填补这一空白，以了解感染库、沙门氏菌宿主适应和传播途径，以便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健康儿童和家畜中的肠炎沙门氏菌，以确定其传播库和沙门氏菌对宿主的适应性。此外，还应对患有侵袭性沙门氏菌病的儿童及其父母进行Exome分析，以发现有助于确定相关代谢途径的风险变量。总体目标如下：·确定动物和人类来源的NTS的频率；·利用全基因组测序检测收集的沙门氏菌分离株基因组的差异；·检测宿主对侵袭性沙门氏菌病的遗传易感性；·确定INT和肠道NTS感染(Ents)的社会经济后果；·加强非洲和非洲-德国合作伙伴内的科学网络，并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.