Rassegna della letteratura scientifica in rivista (Literature review), 2023, ENG, 10.3390/pathogens12020240

The DarT/DarG Toxin-Antitoxin ADP-Ribosylation System as a Novel Target for a Rational Design of Innovative Antimicrobial Strategies

Catara, Giuliana; Caggiano, Rocco; Palazzo, Luca

Consiglio Nazionale delle Ricerche; Università degli Studi di Napoli Federico II

The chemical modification of cellular macromolecules by the transfer of ADP-ribose unit(s), known as ADP-ribosylation, is an ancient homeostatic and stress response control system. Highly conserved across the evolution, ADP-ribosyltransferases and ADP-ribosylhydrolases control ADP-ribosylation signalling and cellular responses. In addition to proteins, both prokaryotic and eukaryotic transferases can covalently link ADP-ribosylation to different conformations of nucleic acids, thus highlighting the evolutionary conservation of archaic stress response mechanisms. Here, we report several structural and functional aspects of DNA ADP-ribosylation modification controlled by the prototype DarT and DarG pair, which show ADP-ribosyltransferase and hydrolase activity, respectively. DarT/DarG is a toxin-antitoxin system conserved in many bacterial pathogens, for example in Mycobacterium tuberculosis, which regulates two clinically important processes for human health, namely, growth control and the anti-phage response. The chemical modulation of the DarT/DarG system by selective inhibitors may thus represent an exciting strategy to tackle resistance to current antimicrobial therapies.

Pathogens 12 (2)

Keywords

ADP-ribosylation, antimicrobial resistance, cell growth, DarT/DarG, DNA modification, phage defence, toxin-antitoxin

CNR authors

Catara Giuliana, Palazzo Luca, Caggiano Rocco

CNR institutes