Table_2_Enteroaggregative Escherichia coli as etiological agent of endemic diarrhea in Spain: A prospective multicenter prevalence study with molecular characterization of isolates.xlsx

BackgroundEnteroaggregative Escherichia coli (EAEC) is increasingly associated with domestically acquired diarrheal episodes in high-income countries, particularly among children. However, its specific role in endemic diarrhea in this setting remains under-recognized and information on molecular characteristics of such EAEC strains is limited. We aimed to investigate the occurrence of EAEC in patients with non-travel related diarrhea in Spain and molecularly characterize EAEC strains associated with illness acquired in this high-income setting.
MethodsIn a prospective multicenter study, stool samples from diarrheal patients with no history of recent travel abroad (n = 1,769) were collected and processed for detection of EAEC and other diarrheagenic E. coli (DEC) pathotypes by PCR. An additional case–control study was conducted among children ≤5 years old. Whole-genome sequences (WGS) of the resulting EAEC isolates were obtained.
ResultsDetection of DEC in the study population. DEC was detected in 23.2% of patients aged from 0 to 102 years, with EAEC being one of the most prevalent pathotypes (7.8%) and found in significantly more patients ≤5 years old (9.8% vs. 3.4%, p < 0.001). Although not statistically significant, EAEC was more frequent in cases than in controls. WGS-derived characterization of EAEC isolates. Sequence type (ST) 34, ST200, ST40, and ST10 were the predominant STs. O126:H27, O111:H21, and O92:H33 were the predominant serogenotypes. Evidence of a known variant of aggregative adherence fimbriae (AAF) was found in 89.2% of isolates, with AAF/V being the most frequent. Ten percent of isolates were additionally classified as presumptive extraintestinal pathogenic E. coli (ExPEC), uropathogenic E. coli (UPEC), or both, and belonged to clonal lineages that could be specifically associated with extraintestinal infections.
ConclusionEAEC was the only bacterial enteric pathogen detected in a significant proportion of cases of endemic diarrhea in Spain, especially in children ≤5 years old. In particular, O126:H27-ST200, O111:H21-ST40, and O92:H33-ST34 were the most important subtypes, with all of them infecting both patients and asymptomatic individuals. Apart from this role as an enteric pathogen, a subset of these domestically acquired EAEC strains revealed an additional urinary/systemic pathogenic potential.

背景：肠聚集性大肠杆菌（Enteroaggregative Escherichia coli, EAEC）在高收入国家的本土获得性腹泻病例中的关联愈发受到关注，尤其在儿童群体中。然而，该菌在该类地区地方性腹泻中的具体致病作用仍未得到充分认识，且相关菌株的分子特征研究信息较为匮乏。本研究旨在调查西班牙非旅行相关性腹泻患者中EAEC的检出情况，并对该高收入地区获得性EAEC感染菌株进行分子特征分析。
方法：本研究为前瞻性多中心研究，收集了1769名无近期境外旅行史的腹泻患者粪便样本，通过聚合酶链式反应（PCR）检测EAEC及其他腹泻肠致病性大肠杆菌（diarrheagenic E. coli, DEC）致病型别。此外，针对≤5岁儿童开展了一项病例对照研究。对分离得到的EAEC菌株进行全基因组测序（Whole-genome sequences, WGS）分析。
结果：1. 研究人群中DEC的检出情况：在0至102岁的所有研究对象中，DEC总检出率为23.2%，其中EAEC为最常见的致病型别之一（7.8%），且在≤5岁儿童中的检出率显著更高（9.8% vs 3.4%，p<0.001）。尽管无统计学差异，但EAEC在病例组中的检出频率高于对照组。2. EAEC菌株的WGS分子特征分析：序列型（Sequence type, ST）34、ST200、ST40及ST10为主要的序列型；O126:H27、O111:H21及O92:H33为主要的血清基因型。89.2%的菌株检出已知的聚集性黏附菌毛（aggregative adherence fimbriae, AAF）变异体，其中以AAF/V最为常见。10%的菌株同时被归类为疑似肠外致病性大肠杆菌（extraintestinal pathogenic E. coli, ExPEC）、尿路致病性大肠杆菌（uropathogenic E. coli, UPEC）或两者兼具，且属于与肠外感染特异性相关的克隆谱系。
结论：在西班牙地方性腹泻病例中，EAEC是在相当比例病例中检出的唯一细菌性肠道致病菌，尤其在≤5岁儿童群体中。其中O126:H27-ST200、O111:H21-ST40及O92:H33-ST34为最主要的亚型，此类菌株既可感染患者也可导致无症状携带。除作为肠道致病菌外，部分社区获得性EAEC菌株还表现出尿路/全身性致病潜能。