**9.1 Symptoms**

*The Universe of Escherichia coli*

In the first stage, an attachment of typical EPEC to the surface of the host intestinal epithelium is mediated by the bundle-forming pili (BFP). The filament EspA also promotes attachment, albeit in a less efficient manner, and could mediate adherence of atypical EPEC strains. In the second stage, Tir and effector proteins (EspB, EspD, EspF, EspG, and Map), translocated into the host cells via type III system apparatus, activate cell-signaling pathways, causing alterations in the host cell cytoskeleton and resulting in actin accumulation and loss of microvilli [58]. In the third stage, bacteria intimately adhered to host cell by intimin-Tir interactions amplifies the accumulation of filaments of actin and other cytoskeletal proteins that result in pedestal-like structures [62, 96, 97]. Finally, the translocated effectors disrupt host cell processes, causing loss of tight-junction integrity and mitochondrial function

Traditionally, the identification of EPEC was based on the O:H serotyping, but serotype designation is no longer precise. The identification of EPEC was based on the characteristic of EPEC's attachment to epithelial cells and may include phenotypic or genotypic tests. The HeLa adherence assay distinguishes EPEC from other *E. coli* by their ability to adhere in a localized pattern (LA) on the surface of cells [8]. The fluorescent actin-staining (FAS) assay, originally described by Knutton et al. [98], leads to the identification of the A/E lesion, by detecting actin condensation under EPEC adhesion pedestals. DNA probes and PCR targeting genes responsible for these characteristics were developed. A 1-kb EAF fragment probe was initially developed as a diagnostic DNA probe (the EAF probe) and subsequently refined as an oligonucleotide probe as well as PCR primers [10, 11, 99]. The identification of *bfpA*, the structural gene encoding BFP, led to the development of more specific and sensitive probe or PCR tests to detect typical EPEC strains [74, 75, 100]. However, some PCR primers may fail to identify all typical EPEC strains since multiple alleles of *bfpA* have been identified [101]. The *eae* sequences by DNA probes and PCR primers have been used to detect the presence

and leading to both electrolyte loss and eventual cell death.

*Four-stage model of EPEC pathogenesis. Reprinted from Clarke et al. [95].*

**58**

of LEE encoding A/E lesion [24].

**8. Diagnosis**

**Figure 2.**

The most common symptoms reported in EPEC infection are watery diarrhea, dehydration, vomiting, food intolerance, and low-grade fever [24, 97]. In addition, EPEC infection may lead to severe malabsorption of nutrients resulting in nutritional aggravation and persistence of diarrhea [102]. Edema, neutrophil infiltrate, and reduced enzymatic activity in the intestinal mucosa have been also found in EPEC infection [103]. EPEC diarrhea often lasts 1–2 weeks but can become persistent, lasting more than 2 weeks, and may result in severe infection [24, 25, 32, 102]. In a recent case-control study, EPEC infection was associated with a 2.8-fold elevated risk of death among infants in Kenya [24, 31, 97].
