Abstract
Cytotoxic necrotizing factor 1 (CNF1) is a bacterial virulence factor, the target of which is represented by Rho GTPases, small proteins involved in a huge number of crucial cellular processes. CNF1, due to its ability to modulate the activity of Rho GTPases, represents a widely used tool to unravel the role played by these regulatory proteins in different biological processes. In this review, we summarized the data available in the scientific literature concerning the observed in vitro effects induced by CNF1. An article search was performed on electronic bibliographic resources. Screenings were performed of titles, abstracts, and full-texts according to PRISMA guidelines, whereas eligibility criteria were defined for in vitro studies. We identified a total of 299 records by electronic article search and included 76 original peer-reviewed scientific articles reporting morphological or biochemical modifications induced in vitro by soluble CNF1, either recombinant or from pathogenic Escherichia coli extracts highly purified with chromatographic methods. Most of the described CNF1-induced effects on cultured cells are ascribable to the modulating activity of the toxin on Rho GTPases and the consequent effects on actin cytoskeleton organization. All in all, the present review could be a prospectus about the CNF1-induced effects on cultured cells reported so far.
Highlights
Cytotoxic necrotizing factor 1 (CNF1) is a bacterial virulence factor associated with some pathogenic Escherichia coli strains causing urinary tract infection and meningitis [1]
The cell-binding domain encompasses two interaction sites in CNF1: an N-terminus domain, which interacts with the 37-kDa laminin receptor precursor (LRP), and a domain directly adjacent to the catalytic domain, which is a high affinity interaction site for the Lutheran (Lu) adhesion glycoprotein/basal cell adhesion molecule (BCAM) Lutheran adhesion glycoprotein/basal cell adhesion molecule (Lu/BCAM) [2,3]
CNF1 is a bacterial protein toxin mainly produced by E. coli, associated with extraintestinal disease, but occasionally detected in intestinal infections [105]
Summary
Cytotoxic necrotizing factor 1 (CNF1) is a bacterial virulence factor associated with some pathogenic Escherichia coli strains causing urinary tract infection and meningitis [1]. It belongs to the cytotoxic necrotizing factors family that includes proteins from E. coli (CNF1, CNF2, and CNF3) and Yersinia pseudotuberculosis (CNFY). CNF1 deamidates a specific glutamine residue, located in the switch 2 domain and involved in GTP hydrolysis (glutamine 63 in RhoA [3,5,6] or 61 in Cdc and Rac1 [7]) and this modification results in the constitutive association of the Rho GTPase with GTP, namely, its constitutive activation
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