Targeting bacterial growth in biofilm conditions: rational design of novel inhibitors to mitigate clinical and food contamination using QSAR

Abstract

Antimicrobial resistance (AMR) is a pressing global issue exacerbated by the abuse of antibiotics and the formation of bacterial biofilms, which cause up to 80% of human bacterial infections. This study presents a computational strategy to address AMR by developing three novel quantitative structure–activity relationship (QSAR) models based on molecular topology to identify potential anti-biofilm and antibacterial agents. The models aim to determine the chemo-topological pattern of Gram (+) antibacterial, Gram (−) antibacterial, and biofilm formation inhibition activity. The models were applied to the virtual screening of a commercial chemical database, resulting in the selection of 58 compounds. Subsequent in vitro assays showed that three of these compounds exhibited the most promising antibacterial activity, with potential applications in enhancing food and medical device safety.

Graphical Abstract

Keywords:

• Biofilm
• bacteria
• antimicrobial
• molecular topology
• QSAR
• food safety
• medical device safety

Acknowledgement

J. Galvez acknowledges support from the MINECO (Spanish Ministry of Economy, Industry, and Competitivity) under Grant number (PID2019-107464RB-C22).

Authors’ contributions

Maria Galvez-Llompart: Conceptualisation, Investigation, Writing – original draft, Writing – review and editing. Jesus Hierrezuelo: Investigation, Writing – original draft, Writing – review and editing. Mariluz Blasco-Santamaría: Investigation. Riccardo Zanni: Writing – original draft, Writing – review and editing. Jorge Gálvez: Writing – review and editing. Antonio de Vicente: Writing – review and editing. Alejandro Pérez: Writing – review and editing. Diego Romero: Conceptualisation, Writing – review and editing. All authors read and approved the final manuscript.

Disclosure statement

The authors report there are no competing interests to declare.

Additional information

Funding

This research was supported by the European Research Council under Grant number (ERC-2014-StG BacBio GA 637971).