Biocomputation and Complex Systems Physics Institute (BIFI)-Joint Unit GBsC-CSIC, University of Zaragoza, Zaragoza, Spain; Departamento de Bioquímica y Biología Molecular y Celular, Faculty of Science, University of Zaragoza, Zaragoza, Spain; Aragon Health Research Institute (IIS Aragón), Zaragoza, Spain
Xuepei Zhang
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden; Chemical Proteomics Unit, Science for Life Laboratory (SciLifeLab), Stockholm, Sweden; Chemical Proteomics, Swedish National Infrastructure for Biological Mass Spectrometry (BioMS), Stockholm, Sweden
Francesca Romana Liberati
Department of Biochemical Sciences “A. Rossi Fanelli”, Sapienza University of Rome, Rome, Italy
Department of Biochemical Sciences “A. Rossi Fanelli”, Sapienza University of Rome, Rome, Italy
Massimiliano Gaetani
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden; Chemical Proteomics Unit, Science for Life Laboratory (SciLifeLab), Stockholm, Sweden; Chemical Proteomics, Swedish National Infrastructure for Biological Mass Spectrometry (BioMS), Stockholm, Sweden
Biocomputation and Complex Systems Physics Institute (BIFI)-Joint Unit GBsC-CSIC, University of Zaragoza, Zaragoza, Spain; Aragon Health Research Institute (IIS Aragón), Zaragoza, Spain; Departamento de Microbiología, Pediatría, Radiología y Salud Pública, Faculty of Medicine, University of Zaragoza, Zaragoza, Spain; CIBER de Enfermedades Respiratorias—CIBERES, Instituto de Salud Carlos III, Madrid, Spain
Biocomputation and Complex Systems Physics Institute (BIFI)-Joint Unit GBsC-CSIC, University of Zaragoza, Zaragoza, Spain; Departamento de Bioquímica y Biología Molecular y Celular, Faculty of Science, University of Zaragoza, Zaragoza, Spain; Aragon Health Research Institute (IIS Aragón), Zaragoza, Spain
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.
