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

Abstract

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.

A modern view of diarrheagenic <i>Escherichia coli</i> — a causative agent of acute intestinal infections

“…Это деление основано на наличии или отсутствии гена aggR, который кодирует активатор транскрипции экспрессии как хромосомных, так и плазмидо-кодируемых факторов вирулентности, включая AAF и дисперзин [39,46]. Высказано предположение, что t-EAgEC имеют больший патогенный потенциал [40,48]. Ряд исследователей указывают на возникновение вспышек диареи, вызванных a-EAgEC [6,14].…”

“…Несмотря на то что такие белковые компоненты, как дисперзин, Pic, ShET1, EAST-1 и Pet, участвуют в вирулентности EAgEC, ни один из них не присутствует во всех штаммах, поэтому предложено использовать triplex-ПЦР для выявле-ния 3 генов (aggR, aatA и aaiA), которая упрощает и унифицирует детекцию EAgEC, включая t-EAgEC и a-EAgEC [14]. В исследовании ряда авторов показано, что комбинация генов вирулентности может зависеть от географического региона [40,48], в связи с этим международный микробиологический надзор за EAgEC может улучшить надлежащий диагностический алгоритм [39].…”

“…Большое количество среди EAgEC штаммов в R-форме является препятствием при серотипировании, приводящим к большому количеству нетипируемых штаммов [14,40,48]. Тем не менее в настоящее время идентифицированы штаммы 11 серологических групп (и серовариантов) EAgEC: О3:Н2; О7:Н -; О15:Н18; О44:Н18; О51:Н11; О77:Н18; О86:Н -; О86:Н2; О111:Н21; О126:Н27; О127:Н2; О144:Н49; ОNT:H21; ОNT:H33, однако они не являются единственными для этой патогруппы DEC.…”

Increased biofilm staining after deletion of sepA in enteroaggregative E. coli strains is not due to the lack of SepA

“…Enteroaggregative Escherichia coli (EAEC) is associated with acute and chronic diarrhea worldwide as well as travelers' diarrhea. [1][2][3][4][5][6][7][8][9][10] Populations strongly affected by EAEC include children in developing countries and deployed military personnel. 1,9,11,12 Globally, diarrhea is the second leading cause of death in children under five.…”

“…25 SepA is a SPATE that is found in 21-60% of EAEC, depending on the study. 5,[26][27][28][29][30] Epidemiological data indicate that SepA may be important for disease caused by EAEC. For example, data from Mali collected during the MAL-ED study showed that sepA was the EAEC gene most strongly associated with diarrheal cases among children under five years of age.…”