Merging Multi-OMICs with Proteome Integral Solubility Alteration Unveils Antibiotic Mode of Action
Merging Multi-OMICs with Proteome Integral Solubility Alteration Unveils Antibiotic Mode of Action
Abstract 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 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.
Rinaldo Serena、Rossi Chiara Scribani、Maity Ritwik、Sancho Javier、Liberati Francesca Romana、Cutruzzol¨¤ Francesca、Zhang Xuepei、A¨ansa Jos¨| Antonio、Gaetani Massimiliano
Department of Biochemical Sciences ?°A. Rossi Fanelli?±, Sapienza University of RomeDepartment of Biochemical Sciences ?°A. Rossi Fanelli?±, Sapienza University of RomeBiocomputation and Complex Systems Physics Institute (BIFI)-Joint Units: BIFI-IQFR (CSIC) and GBsC-CSIC, University of Zaragoza||Departamento de Bioqu¨amica y Biolog¨aa Molecular y Celular, Faculty of Science, University of Zaragoza||Aragon Health Research Institute (IIS Arag¨?n)Biocomputation and Complex Systems Physics Institute (BIFI)-Joint Units: BIFI-IQFR (CSIC) and GBsC-CSIC, University of Zaragoza||Departamento de Bioqu¨amica y Biolog¨aa Molecular y Celular, Faculty of Science, University of Zaragoza||Aragon Health Research Institute (IIS Arag¨?n)Department of Biochemical Sciences ?°A. Rossi Fanelli?±, Sapienza University of RomeDepartment of Biochemical Sciences ?°A. Rossi Fanelli?±, Sapienza University of RomeDepartment of Medical Biochemistry and Biophysics, Karolinska Institutet||Chemical Proteomics Unit, Science for Life Laboratory (SciLifeLab)||Chemical Proteomics, Swedish National Infrastructure for Biological Mass Spectrometry (BioMS)Biocomputation and Complex Systems Physics Institute (BIFI)-Joint Units: BIFI-IQFR (CSIC) and GBsC-CSIC, University of Zaragoza||Aragon Health Research Institute (IIS Arag¨?n)||Departamento de Microbiolog¨aa, Pediatr¨aa, Radiolog¨aa y Salud P¨2blica, Faculty of Medicine, University of Zaragoza||CIBER de Enfermedades Respiratorias?aCIBERES, Instituto de Salud Carlos IIIDepartment of Medical Biochemistry and Biophysics, Karolinska Institutet||Chemical Proteomics Unit, Science for Life Laboratory (SciLifeLab)||Chemical Proteomics, Swedish National Infrastructure for Biological Mass Spectrometry (BioMS)
医学研究方法生物科学研究方法、生物科学研究技术药学
Rinaldo Serena,Rossi Chiara Scribani,Maity Ritwik,Sancho Javier,Liberati Francesca Romana,Cutruzzol¨¤ Francesca,Zhang Xuepei,A¨ansa Jos¨| Antonio,Gaetani Massimiliano.Merging Multi-OMICs with Proteome Integral Solubility Alteration Unveils Antibiotic Mode of Action[EB/OL].(2025-03-28)[2025-05-09].https://www.biorxiv.org/content/10.1101/2023.09.07.556692.点此复制
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