The Intriguing Evolutionary Journey of Enteroinvasive E. coli (EIEC) toward Pathogenicity

Abstract

Among the intestinal pathogenic Escherichia coli, enteroinvasive E. coli (EIEC) are a group of intracellular pathogens able to enter epithelial cells of colon, multiplicate within them, and move between adjacent cells with a mechanism similar to Shigella, the ethiological agent of bacillary dysentery. Despite EIEC belong to the same pathotype of Shigella, they neither have the full set of traits that define Shigella nor have undergone the extensive gene decay observed in Shigella. Molecular analysis confirms that EIEC are widely distributed among E. coli phylogenetic groups and correspond to bioserotypes found in many E. coli serogroups. Like Shigella, also in EIEC the critical event toward a pathogenic life-style consisted in the acquisition by horizontal gene transfer of a large F-type plasmid (pINV) containing the genes required for invasion, intracellular survival, and spreading through the intestinal mucosa. In Shigella, the ample gain in virulence determinants has been counteracted by a substantial loss of functions that, although important for the survival in the environment, are redundant or deleterious for the life inside the host. The pathoadaptation process that has led Shigella to modify its metabolic profile and increase its pathogenic potential is still in infancy in EIEC, although maintenance of some features typical of E. coli might favor their emerging relevance as intestinal pathogens worldwide, as documented by recent outbreaks in industrialized countries. In this review, we will discuss the evolution of EIEC toward Shigella-like invasive forms going through the epidemiology, including the emergence of new virulent strains, their genome organization, and the complex interactions they establish with the host.

Keywords: Shigella; bacterial evolution; emerging EIEC; enteroinvasive E. coli (EIEC); pathogenic E. coli.

FIGURE 1

Genetic map of the pINV of Shigella and EIEC strains. The red arrows indicate major virulence determinants. Due to the variability in position and number, the ipaH genes are not shown. The genetic organization of the entry region is shown in detail, with dashed arrow lines indicating known transcriptional units. The entry region organization is based on the sequence of plasmid pWR100 (Venkatesan et al., 2001) while the entire plasmid is freely drawn to provide the layout of a typical pINV plasmid (the figure is not to scale).

FIGURE 2

Genetic events contributing to the evolution of EIEC from ancestral commensal E. coli. The acquisition of the pINV by HGT is a major evolutionary event toward pathogenicity. This can be accompanied by the sporadic acquisition of entire or incomplete SHI-1 PAI and incomplete SHI-2 and SHI-3 PAIs. Rarely, also incomplete SRL PAI are acquired by EIEC genomes. The absence of ompT and the loss of cadaverine synthesis (usually resulting from cadC silencing) counterbalance the gain of virulence-associated determinants. The inactivation of speG (involved in spermidine acetylation) and nad (involved in NAD biosynthesis) is regarded as emergent pathoadaptive mutations in EIEC.