Merging multi-omics with proteome integral solubility alteration unveils antibiotic mode of action
Year: 2024
Type: article
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 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.
Source: eLife
Institutions: Universidad de Zaragoza, Instituto de Investigación Sanitaria Aragón, Instituto de Biocomputación y Física de Sistemas Complejos, Science for Life Laboratory, Karolinska Institutet, Sapienza University of Rome, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Enfermedades Respiratorias
Language: English
Subfield: Spectroscopy
Field: Chemistry
Domain: Physical Sciences
Open Access status: gold
Estimated APC paid: $2,500
Funders: Joint Programming Initiative on Antimicrobial Resistance, Ministerio de Ciencia, Innovación y Universidades, European Commission, Karolinska Institutet, Ministerio de Ciencia e Innovación, Science for Life Laboratory, Gobierno de Aragón, Horizon 2020 Framework Programme, Division of Chemistry, H2020 Marie Skłodowska-Curie Actions
Awards: International Doctoral Programme for Talent Attraction to the Campus of International Excellence of the Ebro Valley, Protein targets and bioactive compounds (ProtBioCom), G2182456869, G2554462488, MOlecular-Scale Biophysics Research Infrastructure, G3690828678, G3844422142, G434337789, G4497392793, G4903200894, G4937468798, G5175525644, G6112762287, G6737779160, G8313865338, G8920660035
OpenAlex ID: W4402925043