Vascon Filippo, De Felice Sofia, Gasparotto Matteo, Huber Stefan T, Catalano Claudio, Chinellato Monica, Mezzetti Riccardo, Grinzato Alessandro, Filippini Francesco, Maso Lorenzo, Jakobi Arjen J, Cendron Laura
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.
iScience. 2025 Jan 2;28(2):111726. doi: 10.1016/j.isci.2024.111726. eCollection 2025 Feb 21.
Antimicrobial resistance poses a severe threat to human health and 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 binding and functional assays, we elucidated the molecular events activating the SOS response in , 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 -derived approaches, to address the implications of infections.
抗菌耐药性对人类健康构成严重威胁，在引发这一紧急情况的病原体中尤为突出。对DNA损伤的SOS反应在细菌进化中至关重要，影响耐药性的发展以及在具有挑战性的环境中的适应性，尤其是在抗生素暴露的情况下。重组酶A（RecA）和转录阻遏物LexA是协调这一过程的关键因素，决定着其控制下基因的沉默或活性转录。通过将最先进的结构方法与结合和功能分析相结合，我们阐明了激活大肠杆菌SOS反应的分子事件，重点关注RecA-LexA相互作用。我们的研究结果确定了使RecA触发LexA自切割和失活的相互作用的保守决定因素和强度。这些结果为设计新型抗菌策略以及探索源自大肠杆菌的方法的潜在转化奠定了基础，以应对大肠杆菌感染的影响。
