Snapshots ofPseudomonas aeruginosaSOS response activation complex reveal structural prerequisites for LexA engagement and cleavage

Filippo Vascon, Sofia De Felice, Matteo Gasparotto, Stefan T. Huber, Claudio Catalano, Monica Chinellato, Alessandro Grinzato, Francesco Filippini, Lorenzo Maso, Arjen J. Jakobi, Laura Cendron

Abstract: h3>Abstract</h3> <p>Antimicrobial resistance represents a major threat to human health and <i>Pseudomonas aeruginosa</i> stands out among the pathogens responsible for this emergency. The SOS response to DNA damage plays a pivotal role in bacterial evolution, driving the development of resistance mechanisms and influencing the adaptability of bacterial populations to challenging environments, particularly in the context of antibiotic exposure. Recombinase A (RecA) and the transcriptional repressor LexA are the key players that orchestrate this process, determining either the silencing or the active transcription of the genes under their control. By integrating state-of-the-art structural approaches with binding and functional assays <i>in vitro</i>, we elucidated the molecular events governing the SOS response activation in <i>P. aeruginosa</i>, focusing on the RecA-LexA interaction. Our findings identify the conserved determinants and strength of the interactions that let RecA trigger the autocleavage and inactivation of the LexA repressor. These results provide the groundwork for designing novel antimicrobial strategies and for exploring the potential translation of <i>Escherichia coli</i>-derived approaches, to address the health-threatening implications of bacterial infections.</p><h3>Graphical Abstract</h3>

External IDs:doi:10.1101/2024.03.22.585941