Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, USA.
University of Maryland School of Medicine, Institute for Genome Sciences, Department of Microbiology and Immunology, Baltimore, Maryland, USA.
Infect Immun. 2021 Feb 16;89(3). doi: 10.1128/IAI.00619-20.
Typical enteropathogenic (tEPEC) is a leading cause of diarrhea and associated death in children worldwide. Atypical EPEC (aEPEC) lacks the plasmid encoding bundle-forming pili and is considered less virulent, but the molecular mechanism of virulence is poorly understood. We recently identified kittens as a host for aEPEC where intestinal epithelial colonization was associated with diarrheal disease and death. The purposes of this study were to (i) determine the genomic similarity between kitten aEPEC and human aEPEC isolates and (ii) identify genotypic or phenotypic traits associated with virulence in kitten aEPEC. We observed no differences between kitten and human aEPEC in core genome content or gene cluster sequence identities, and no distinguishing genomic content was observed between aEPEC isolates from kittens with nonclinical colonization (NC) versus those with lethal infection (LI). Variation in adherence patterns and ability to aggregate actin in cultured cells mirrored descriptions of human aEPEC. The aEPEC isolated from kittens with LI were significantly more motile than isolates from kittens with NC. Kittens may serve as a reservoir for aEPEC that is indistinguishable from human aEPEC isolates and may provide a needed comparative animal model for the study of aEPEC pathogenesis. Motility seems to be an important factor in pathogenesis of LI associated with aEPEC in kittens.
典型肠致病性大肠杆菌(tEPEC)是全球儿童腹泻和相关死亡的主要原因。非典型肠致病性大肠杆菌(aEPEC)缺乏编码束形成菌毛的质粒,被认为毒力较低,但毒力的分子机制知之甚少。我们最近发现,小猫是 aEPEC 的宿主,其肠道上皮定植与腹泻病和死亡有关。本研究的目的是:(i)确定小猫 aEPEC 与人类 aEPEC 分离株之间的基因组相似性;(ii)确定与小猫 aEPEC 毒力相关的基因型或表型特征。我们观察到小猫和人类 aEPEC 在核心基因组内容或基因簇序列同一性方面没有差异,并且在非临床定植(NC)与致死性感染(LI)的小猫的 aEPEC 分离株之间没有观察到区别性的基因组内容。在培养细胞中的粘附模式和聚集肌动蛋白的能力的变化与对人类 aEPEC 的描述一致。从 LI 小猫中分离出的 aEPEC 比从 NC 小猫中分离出的 aEPEC 具有更高的迁移能力。小猫可能是 aEPEC 的储存库,与人类 aEPEC 分离株无法区分,并且可能为研究 aEPEC 发病机制提供了一种必要的比较动物模型。运动性似乎是与小猫中 aEPEC 相关的 LI 发病机制中的一个重要因素。