Snapshots of Pseudomonas aeruginosa SOS response reveal structural requisites for LexA autoproteolysis
Filippo Vascon,
Sofia De Felice,
Matteo Gasparotto,
Stefan T. Huber,
Claudio Catalano,
Monica Chinellato,
Riccardo Mezzetti,
Alessandro Grinzato,
Francesco Filippini,
Lorenzo Maso,
Arjen J. Jakobi,
Laura Cendron
Affiliations
Filippo Vascon
Department of Biology, University of Padua, Via Ugo Bassi 58/b, 35131 Padova, Italy
Sofia De Felice
Department of Biology, University of Padua, Via Ugo Bassi 58/b, 35131 Padova, Italy
Matteo Gasparotto
Department of Biology, University of Padua, Via Ugo Bassi 58/b, 35131 Padova, Italy; Department of Translational Brain Research, Central Institute of Mental Health (ZI), University of Heidelberg/Medical Faculty Mannheim, 68159 Mannheim, Germany
Stefan T. Huber
Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, 2628CD Delft, the Netherlands
Claudio Catalano
NanoImaging Services, 4940 Carroll Canyon Road, Suite 115, San Diego, CA 92121, USA
Monica Chinellato
Department of Biology, University of Padua, Via Ugo Bassi 58/b, 35131 Padova, Italy; Department of Medicine, University of Padua, Via Giustiniani 2, 35121 Padova, Italy
Riccardo Mezzetti
Department of Biology, University of Padua, Via Ugo Bassi 58/b, 35131 Padova, Italy
Alessandro Grinzato
Department of Biology, University of Padua, Via Ugo Bassi 58/b, 35131 Padova, Italy; CM01 Beamline, European Synchrotron Radiation Facility (ESRF), Grenoble, France
Francesco Filippini
Department of Biology, University of Padua, Via Ugo Bassi 58/b, 35131 Padova, Italy
Lorenzo Maso
Department of Biology, University of Padua, Via Ugo Bassi 58/b, 35131 Padova, Italy; Aethon Therapeutics, Long Island City, NY 11101, USA
Arjen J. Jakobi
Department of Bionanoscience, Kavli Institute of Nanoscience, Delft University of Technology, 2628CD Delft, the Netherlands
Laura Cendron
Department of Biology, University of Padua, Via Ugo Bassi 58/b, 35131 Padova, Italy; Corresponding author
Summary: Antimicrobial resistance poses a severe threat to human health and Pseudomonas aeruginosa stands out among the pathogens responsible for this emergency. The SOS response to DNA damage is crucial in bacterial evolution, influencing resistance development and adaptability in challenging environments, especially under 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 in vitro binding and functional assays, we elucidated the molecular events activating the SOS response in P. aeruginosa, focusing on the RecA-LexA interaction. Our findings identify the conserved determinants and strength of the interactions that allow RecA to trigger LexA autocleavage and inactivation. These results provide the groundwork for designing novel antimicrobial strategies and exploring the potential translation of Escherichia coli-derived approaches, to address the implications of P. aeruginosa infections.
