145462 20250908131442.0 doi 10.7554/eLife.96343 sideral 140331 ART-2024-140331 eng Maity, Ritwik (orcid)0000-0003-4058-2888 Merging multi-omics with proteome integral solubility alteration unveils antibiotic mode of action 2024 Access copy available to the general public Unrestricted Antimicrobial resistance is responsible for an alarming number of deaths, estimated at 5 million per year. To combat priority pathogens, like Helicobacter pylori, the development of novel therapies is of utmost importance. Understanding the molecular alterations induced by medications is critical for the design of multi-targeting treatments capable of eradicating the infection and mitigating its pathogenicity. However, the application of bulk omics approaches for unraveling drug molecular mechanisms of action is limited by their inability to discriminate between target-specific modifications and off-target effects. This study introduces a multi-omics method to overcome the existing limitation. For the first time, the Proteome Integral Solubility Alteration (PISA) assay is utilized in bacteria in the PISA-Express format to link proteome solubility with different and potentially immediate responses to drug treatment, enabling us the resolution to understand target-specific modifications and off-target effects. This study introduces a comprehensive method for understanding drug mechanisms and optimizing the development of multi-targeting antimicrobial therapies. info:eu-repo/grantAgreement/ES/DGA/E45-23R info:eu-repo/grantAgreement/EC/H2020/801586/EU/International Doctoral Programme for Talent Attraction to the Campus of International Excellence of the Ebro Valley/IberusTalent This project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No H2020 801586-IberusTalent info:eu-repo/grantAgreement/ES/MICINN/PID2019-107293GB-I00 info:eu-repo/grantAgreement/ES/MICINN/PID2022-141068NB-I00 info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 3.379 2024 Biochemistry, Genetics and Molecular Biology (miscellaneous) 2024 Q1 Neuroscience (miscellaneous) 2024 Q1 Medicine (miscellaneous) 2024 Q1 Immunology and Microbiology (miscellaneous) 2024 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Zhang, Xuepei Liberati, Francesca Romana Scribani Rossi, Chiara Cutruzzolá, Francesca Rinaldo, Serena Gaetani, Massimiliano Aínsa, José Antonio Universidad de Zaragoza (orcid)0000-0003-2076-844X Sancho, Javier Universidad de Zaragoza (orcid)0000-0002-2879-9200 1011 630 Universidad de Zaragoza Dpto. Microb.Ped.Radio.Sal.Pú. Área Microbiología 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 13 (2024), 21 pp. eLife (Cambridge) eLife 2050-084X 7248801 http://zaguan.unizar.es/record/145462/files/texto_completo.pdf Versión publicada 2601053 http://zaguan.unizar.es/record/145462/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:145462 articulos driver 2025-09-08-12:59:49 ARTICLE