Effects of the Escherichia coli Bacterial Toxin Cytotoxic Necrotizing Factor 1 on Different Human and Animal Cells: A Systematic Review

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.

Characterization of Diarreaghenic Escherichia coli Strains Isolated from Healthy Donors, including a Triple Hybrid Strain

“…Interestingly, four of these strains produced higher levels than the control strain and could represent an important feature in the pathogenic process as well as the role that biofilm represents in terms of antimicrobial resistance. An interesting finding was the identification of four of the strains as hyper-producers of biofilm; this may be associated with high levels of antibiotic resistance in an infectious process, as has been previously reported [32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50]. However, further testing will be necessary to prove such an assertion.…”

Interactions of Bacterial Toxin CNF1 and Host JAK1/2 Driven by Liquid-Liquid Phase Separation Enhance Macrophage Polarization

“…It has been demonstrated that the C-terminal catalytic domain (amino acids 720 to 1014) interferes with Rho GTPases (Rho, Rac, and Cdc42) ( 39 ). CNF1 deamidates a specific glutamine residue located in the switch 2 domain of G proteins (glutamine 63 in RhoA or glutamine 61 in Cdc42 and Rac1) ( 40 ), and this modification results in the constitutive activation of these proteins on their effectors, which are involved in several cellular processes, such as the modulation of cytoskeletal dynamics, gene transcription, cell adhesion, cell migration, cell polarity, and cell cycle progression ( 41 ).…”

Activation of Focal Adhesion Kinase Restores Simulated Microgravity-Induced Inhibition of Osteoblast Differentiation via Wnt/Β-Catenin Pathway

“…The control cells were placed in the incubator under 1-g conditions. CNF1 has been extensively used to treat mammalian cells in cell cultures at concentrations ranging between 10 and 100 ng/mL for measurement of CNF1’s effect on molecular pathway modulations [ 54 , 55 , 56 ]. To assess conversional effect of CNF1 on SMG, we chose to add an intermediate dose of CNF1 (30 ng/mL) to the above MC3T3-E1 cells cultured under SMG, as we previously described [ 16 , 17 ].…”