Enteropathogenic and Enterohemorrhagic Escherichia coli Type III Secretion Effector EspV Induces Radical Morphological Changes in Eukaryotic Cells

Abstract

Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic Escherichia coli (EHEC) are important human pathogens that rely on translocation of type III secretion system (T3SS) effectors for subversion of signal transduction pathways and colonization of the mammalian gut mucosa. While a core set of effectors is conserved between EPEC and EHEC strains, a growing number of accessory effectors that were found at various frequencies in clinical and environmental isolates have been recently identified. Recent genome projects identified espV as a pseudogene in EHEC but a putative functional gene in EPEC strains E110019 and E22 and the closely related mouse pathogen Citrobacter rodentium. The aim of this study was to determine the distribution of espV among clinical EPEC and EHEC strains and to investigate its function and role in pathogenesis. espV was found in 16% of the tested strains. While deletion of espV from C. rodentium did not affect colonization dynamics or fitness in mixed infections, expression of EspV in mammalian cells led to drastic morphological alterations, which were characterized by nuclear condensation, cell rounding, and formation of dendrite-like projections. Expression of EspV in yeast resulted in a dramatic increase in cell size and irreversible growth arrest. Although the role of EspV in infection and its target host cell protein(s) require further investigation, the data point to a novel mechanism by which the T3SS subverts cell signaling.

Escherichia coli Serotype O55:H7 Diversity Supports Parallel Acquisition of Bacteriophage at Shiga Toxin Phage Insertion Sites during Evolution of the O157:H7 Lineage

“…In order to identify additional O157:H7 strains that had inconsistent patterns of stx 1 and stx 2 presence, we tested 22 O157:H7 strains, half of which were environmental isolates and half of which were clinical isolates (4 stx negative and 18 carrying stx 1 only) for sorbitol utilization, GUD function, fimA deletion, and fimH mutation, as well as occupancy of stx phage insertion sites…”

Infection strategies of enteric pathogenic Escherichia coli

“…In addition EHEC produces Stx, the action of which is described in Figure 3B. Another T3SS effector, EspV present in EPEC strains E110019 and E22 is able to cause nuclear condensation, cell rounding and actin-rich dendrite-like projections upon overexpression in mammalian cells 155 although the mechanisms involved in this actin rearrangement are not yet known.…”

The enteropathogenic E. coli effector EspH promotes actin pedestal formation and elongation via WASP-interacting protein (WIP)

“…This question is not limited to EspH as phenotypes of other cytoskeletal‐modulating T3SS effectors, e.g. EspV (Arbeloa et al ., 2011), EspT (Bulgin et al ., 2009) and EspM (Arbeloa et al ., 2008), could only be seen using in vitro cell models following overexpression. This might reflect the existence of a complex regulatory mechanism of effectors expression and translocation in vivo , which we do not yet understand, that the cell culture conditions do not mimic.…”