Population genomics and evolution of Avian Pathogenic E. coli

Chickens are the most common birds on earth and colibacillosis in among the most common diseases affecting them. This major threat to animal welfare and safe sustainable food production is difficult to combat because the etiological agent, avian pathogenic<i> Escherichia coli </i>(APEC), emerges from ubiquitous commensal gut bacteria, with no one virulence gene present in all pathogenic isolates. Here we address the underlying evolutionary mechanisms of extraintestinal spread and systemic infection. Combining population scale comparative genomics and pangenome-wide association studies, we compare <i>E. coli </i>from commensal carriage and systemic infections. We identify phylogroup-specific and species-wide genetic elements that are enriched in APEC, including pathogenicity-associated variation in 143 genes that have diverse predicted functions, including genes involved in metabolism, lipopolysaccharide synthesis, heat shock response, antimicrobial resistance and toxicity. Horizontal gene transfer spreads pathogenicity elements, allowing divergent clones to cause infection. Finally, Random Forest model prediction of disease status (carriage vs. disease) identifies pathogenicity elements in the emergent ST-117 poultry-associated lineage with 73% accuracy, demonstrating the potential for early identification emergent APEC in healthy flocks.

鸡是地球上最常见的鸟类，而鸡大肠杆菌病（colibacillosis）是影响它们的最常见疾病之一。该疾病对动物福利与安全可持续粮食生产构成重大威胁，防控难度极高，其病原为禽致病性大肠杆菌（avian pathogenic Escherichia coli, APEC）——该菌由无处不在的共生肠道大肠杆菌演化而来，且所有致病分离株中不存在统一的毒力基因。本研究旨在阐明其肠外扩散与全身性感染的潜在演化机制。本研究结合群体规模比较基因组学与泛基因组全关联分析，对比了共生定植与全身性感染来源的大肠杆菌。研究鉴定出在APEC中富集的进化枝特异性及物种范围的遗传元件，包括143个功能多样的毒力相关变异基因，其预测功能涵盖代谢、脂多糖合成、热休克应答、抗菌药物耐药性与毒性等。水平基因转移介导了毒力元件的传播，使得不同演化克隆也可引发感染。最后，基于随机森林（Random Forest）模型对定植/发病状态的预测，本研究以73%的准确率在新兴的ST-117禽源谱系中鉴定出毒力元件，证明了在健康鸡群中早期识别新兴APEC的应用潜力。