Antimicrobial resistance and gene regulation in Enteroaggregative Escherichia coli from Egyptian children with diarrhoea: Similarities and differences.

Antimicrobial resistance and gene regulation in Enteroaggregative Escherichia coli from Egyptian children with diarrhoea: Similarities and differences.
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DOI:
10.1080/21505594.2020.1859852
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发表时间:
2021-12
期刊:
影响因子:
5.2
通讯作者:
Browning DF
Browning DF
中科院分区:
生物学2区
文献类型:
--
作者:
Abdelwahab R;Yasir M;Godfrey RE;Christie GS;Element SJ;Saville F;Hassan EA;Ahmed EH;Abu-Faddan NH;Daef EA;Busby SJW;Browning DF

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肠聚集性大肠埃希菌(EAEC)是一种常见的人类致泻性病原体,从发展中国家和工业化国家的患者中分离出来,对许多一线抗生素的耐药性越来越强。在这项研究中,我们从埃及阿西亚特大学儿童医院门诊的腹泻儿童中筛选出50株大肠杆菌。我们发现所有这些分离株都对多种抗生素具有耐药性,并鉴定出两株典型的EAEC菌株。通过全基因组测序,我们确定这两个分离株都携带blaCTX-M和blaTEM抗生素耐药性基因,以及许多经典的EAEC毒力决定因素,包括转录调控因子agR。我们证明这些毒力决定因素的表达依赖于AggR,包括编码AggR抑制物AAR的AAR。由于生物膜形成是EAEC感染的标志,我们研究了AAR过表达对生物膜形成和AggR依赖基因表达的影响。我们发现,虽然AAR对AggR依赖的转录影响很小,但它能够完全破坏生物膜的形成,这表明AAR对这两个过程的影响是不同的。综上所述,我们的结果建议了一个诱导EAEC毒力基因表达的模型,该模型可以解释EAEC在疾病和健康个体中普遍存在的原因。
Enteroaggregative Escherichia coli (EAEC) is a common diarrhoeagenic human pathogen, isolated from patients in both developing and industrialized countries, that is becoming increasingly resistant to many frontline antibiotics. In this study, we screened 50 E. coli strains from children presenting with diarrhea at the outpatients clinic of Assiut University Children’s Hospital, Egypt. We show that all of these isolates were resistant to multiple classes of antibiotics and identified two as being typical EAEC strains. Using whole genome sequencing, we determined that both isolates carried, amongst others, blaCTX-M and blaTEM antibiotic resistance genes, as well as many classical EAEC virulence determinants, including the transcriptional regulator, AggR. We demonstrate that the expression of these virulence determinants is dependent on AggR, including aar, which encodes for a repressor of AggR, Aar. Since biofilm formation is the hallmark of EAEC infection, we examined the effect of Aar overexpression on both biofilm formation and AggR-dependent gene expression. We show that whilst Aar has a minimal effect on AggR-dependent transcription it is able to completely disrupt biofilm formation, suggesting that Aar affects these two processes differently. Taken together, our results suggest a model for the induction of virulence gene expression in EAEC that may explain the ubiquity of EAEC in both sick and healthy individuals.
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