Clever Cooperation: Interactions Between EspF and Host Proteins

Abstract

EspF is a central effector protein of enterohemorrhagic Escherichia coli (EHEC), enteropathogenic E. coli (EPEC), and Citrobacter rodentium (CR) that is secreted through the type III secretion system to host cells. The interaction between EspF and host proteins plays an important role in bacterial pathogenesis. EspF protein binds to host SNX9 and N-WASP proteins to promote the colonization of pathogenic bacteria in intestinal epithelial cells; combines with cytokeratin 18, actin, 14-3-3ζ, Arp2/3, profilin, and ZO-1 proteins to intervene in the redistribution of intermediate filaments, the rearrangement of actin, and the disruption of tight junctions; acts together with Abcf2 to boost host cell intrinsic apoptosis; and collaborates with Anxa6 protein to inhibit phagocytosis. The interaction between EspF and host proteins is key to the pathogenic mechanism of EHEC and EPEC. Here, we review how EspF protein functions through interactions with these 10 host proteins and contributes to the pathogenicity of EHEC/EPEC.

ABC-F proteins in mRNA translation and antibiotic resistance

“…ABCF1 is believed to be an important regulator of the innate immune response to viral DNA and RNA [50]. The ABCF2 protein has been linked to bacterial infection [51] as well as cancer [48], but its role in these processes is unclear.…”

Enteropathogenic Escherichia coli (EPEC) Recruitment of PAR Polarity Protein Atypical PKCζ to Pedestals and Cell–Cell Contacts Precedes Disruption of Tight Junctions in Intestinal Epithelial Cells

“…For instance, EspF recruits clathrin, AP2, early (Rab5a and EEA1) and recycling (Rab4a, Rab11a, Rab11b, FIP2, Myo5b) endocytic proteins to sites of infection [38]. The EspF binding partner SNX9 is recruited to clathrin-coated pits and associates with N-WASP, dynamin, Arp2/3 and other associated proteins to promote endocytosis of plasma membrane receptors [64][65][66][67][68][69]. In addition, EPEC mediates Crb3 endocytosis in a dynamin-dependent manner [32].…”

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“…The N-terminal domain of the EspF protein plays a decisive role in EspF's targeting to mitochondria and nucleoli of host cells. In contrast, the C-terminal domain contains the primary protein-binding site with SNX9 and N-WASP (Hua et al, 2018a) ( Figure 1A). It remains unknown which domain acts in the binding to ANXA6.…”

“…The depolymerization of actin destructs TJ through caveolin-mediated endocytosis of occludin (Shen and Turner, 2005). EspF may combine with Calmodulin through 14-3-3ζ to activate and phosphorylate MLC, thereby disturbing the TJ barrier process (Hua et al, 2018a). A previous study revealed that EspF's binding to SNX9 could reorganize the actin pedestal, recruit active aPKC to actin at cell-cell borders, and promote endocytosis of occludin, thus destabilizing polarity complexes, which ultimately results in TJ perturbation (Weflen et al, 2009).…”