<b>Emergence of hybrid </b><b><i>Escherichia coli</i></b><b> with dual disease manifestations in i</b><b>ntestinal and extraintestinal niches</b>-<b>Raw Data</b>

<i>Escherichia coli</i>, a significant zoonotic pathogen, continuously evolves to produce hybrid strains with diverse pathogenic characteristics, threatening public health. Hybrid <i>E. coli </i>strains can cause multiple diseases in various tissues within a single individual or among different hosts with diverse genetic backgrounds. These strains have been reported to exhibit higher virulence, enhanced infectiousness, and increased resistance to environmental clearance. Here we identified a hybrid aEPEC/ExPEC isolate, PE164, from the blood and bloody stool of a piglet with severe diarrhea, which exhibited both intestinal and extraintestinal pathogenic traits. Monitoring the emergence of PE164-like hybrids in porcine-derived <i>E. coli </i>is crucial for animal production and public health safety. Phylogenetic and virulence gene analyses of nearly 300 clinical isolates from diseased pigs revealed eight hybrid strains categorized into four types, with significant variations in pathogenicity identified by <i>in vitro</i> and <i>in vivo</i> models. Notably, two O108 isolates, PE150 and PE164, were classified as highly virulent strains. A fused gene cluster of colanic acid and O108 antigen biosynthesis (CAO108) was identified as a key determinant of their extraintestinal pathogenicity, raising concerns about O-antigens linked to other exopolysaccharide components to create new high virulence factors. Additionally, the type III secretion system (T3SS), a classic pathway for pathogenic <i>E. coli</i> to optimally colonize the host gut, enhanced bacterial immune evasion and contributed to the extraintestinal pathogenicity of PE164. These findings underscore the prevalence of hybrid pathogenic <i>E. coli</i> strains in pigs, presenting new challenges for disease control.

大肠杆菌（Escherichia coli）作为一种重要的人畜共患病原菌，持续进化出具备多样致病特征的杂交菌株，对公共卫生安全构成威胁。杂交型大肠杆菌菌株可在单一宿主的不同组织内，或感染不同遗传背景的宿主时引发多种疾病。据报道，此类菌株具有更强的毒力、更高的感染性，且对环境清除作用的抗性更强。本研究从患有重度腹泻的仔猪血液及血性粪便中分离鉴定得到一株杂交型粘附性肠致病性大肠杆菌/肠外致病性大肠杆菌（aEPEC/ExPEC）分离株PE164，该菌株同时具备肠道致病性与肠外致病性特征。监测猪源大肠杆菌中PE164类杂交菌株的出现情况，对动物养殖与公共卫生安全均至关重要。对近300株病猪临床分离株开展系统发育与毒力基因分析后，共鉴定出8株杂交型菌株，可分为4个亚型；通过体外（in vitro）与体内（in vivo）模型检测发现，这些菌株的致病性存在显著差异。值得注意的是，两株O108血清型分离株PE150与PE164被归类为高毒力菌株。编码荚膜多糖（colanic acid）与O108抗原（O108 antigen）生物合成的融合基因簇（CAO108）被确定为其肠外致病性的关键决定因素，这引发了学界对O抗原与其他胞外多糖组分结合形成新型高毒力因子的担忧。此外，III型分泌系统（type III secretion system, T3SS）作为致病性大肠杆菌优化宿主肠道定植的经典通路，可增强细菌的免疫逃逸能力，并助力PE164的肠外致病性。上述研究结果凸显了猪源杂交型致病性大肠杆菌的流行态势，为疾病防控带来了新的挑战。