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.

Merging multi-OMICs with proteome integral solubility alteration unveils antibiotic mode of action / Maity, Ritwik; Zhang, Xuepei; Liberati, Francesca Romana; Rossi, Chiara Scribani; Cutruzzola', Francesca; Rinaldo, Serena; Gaetani, Massimiliano; Aínsa, José Antonio; Sancho, Javier. - In: ELIFE. - ISSN 2050-084X. - 13:(2024). [10.7554/elife.96343.3]

Merging multi-OMICs with proteome integral solubility alteration unveils antibiotic mode of action

Maity, Ritwik;Liberati, Francesca Romana;Rossi, Chiara Scribani;Cutruzzola', Francesca;Rinaldo, Serena;
2024

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.
2024
CagA; FtsZ; Helicobacter pylori; antimicrobial resistance; computational biology; infectious disease; microbiology; multi-omics; systems biology; target deconvolution
01 Pubblicazione su rivista::01a Articolo in rivista
Merging multi-OMICs with proteome integral solubility alteration unveils antibiotic mode of action / Maity, Ritwik; Zhang, Xuepei; Liberati, Francesca Romana; Rossi, Chiara Scribani; Cutruzzola', Francesca; Rinaldo, Serena; Gaetani, Massimiliano; Aínsa, José Antonio; Sancho, Javier. - In: ELIFE. - ISSN 2050-084X. - 13:(2024). [10.7554/elife.96343.3]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1721744
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