AtaT Improves the Stability of Pore-Forming Protein EspB by Acetylating Lysine 206 to Enhance Strain Virulence

Abstract

A novel type II toxin of toxin–antitoxin systems (TAs), Gcn5-related N-acetyltransferase (GNAT) family, was reported recently. GNAT toxins are mainly present in pathogenic species, but studies of their involvement in pathogenicity are rare. This study discovered that the GANT toxin AtaT in enterohemorrhagic Escherichia coli (EHEC) can significantly enhance strain pathogenicity. First, we detected the virulence of ΔataT and ΔataR in cell and animal models. In the absence of ataT, strains showed a lower adhesion number, and host cells presented weaker attaching and effacing lesions, inflammatory response, and pathological injury. Next, we screened the acetylation substrate of AtaT to understand the underlying mechanism. Results showed that E. coli pore-forming protein EspB, which acts as a translocon in type III secretion system (T3SS) in strains, can be acetylated specifically by AtaT. The acetylation of K206 in EspB increases protein stability and maintains the efficiency of effectors translocating into host cells to cause close adhesion and tissue damage.

The novel type II toxin–antitoxin PacTA modulates Pseudomonas aeruginosa iron homeostasis by obstructing the DNA-binding activity of Fur

“…PacT can directly target the N-terminal HTH domain of Fur through protein–protein interactions without acetylation modification, but the binding of PacT obviously decreased the DNA-binding ability of Fur. Although it has been found that AtaT could specifically acetylate residue K206 in EspB to enhance protein stability and bacterial virulence in enterohemorrhagic E. coli ( 54 ), structural analysis showed that PacT (PDB: 1YRE) adapted a relatively more compact conformation, in which the substrate access channel was too narrow to accommodate protein substrate ( Supplementary Figure S10 ). Therefore, PacT-Fur coupling is somehow analogous to the toxin-antitoxin interaction in type II TA systems such as HigBA and VapBC ( 31 , 55 ), suggesting that type II TA toxin may recognize various proteins other than its cognate antitoxins.…”

Genomic and Transcriptomic Analysis Reveal Multiple Strategies for the Cadmium Tolerance in Vibrio parahaemolyticus N10-18 Isolated from Aquatic Animal Ostrea gigas Thunberg

“…Of these, the GNAT ( Vp_N10_18_4551 ) belongs to type II toxin of toxin–antitoxin systems. The GNAT toxin blocks protein translation by acetylating the amino group of charged tRNAs, thus preventing tRNA from participating in peptidyl ribosomal transferase [ 92 ].…”

B7 Family Molecule VSIG4 Regulates Intestinal Anti-Enterohemorrhagic Escherichia coli Immunity by Altering Gut Flora Diversity

“…Considering Het is a more rigorous control, our subsequent analyses were based on the comparison between Het and KO group. At 36 h, the inflammatory cytokines KC (keratinocyte-derived cytokine, IL-8) in serum were detected, which is the main inflammatory factor response to EHEC infection [ 21 , 22 ]. We found that the KC in infected mice increased significantly, and the level of inflammatory reaction in Het infection group was significantly higher than that in KO infection group ( Figure 1 D), which was consistent with the colonization of pathogens.…”