Druggability analysis of protein targets for drug discovery to combat Listeria monocytogene

Authors: HANES, ROBERT - Villanova University; Liu, Yanhong; HUANG, ZUYI - Villanova University

Submitted to: Microorganisms
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 5/21/2024
Publication Date: 5/25/2024
Citation: Hanes, R., Liu, Y., Huang, Z. 2024. Druggability analysis of protein targets for drug discovery to combat Listeria monocytogene. Microorganisms. 12(6):1073. https://doi.org/10.3390/microorganisms12061073.
DOI: https://doi.org/10.3390/microorganisms12061073

Interpretive Summary: Listeria monocytogenes is an important foodborne pathogen. Previous research has identified certain proteins in L. monocytogenes that are crucial for stress response, ability to cause disease (virulence), and resistance to antibiotics. These proteins are considered potential targets for developing new strategies to eliminate L. monocytogenes. However, their ability as drug targets ("druggability") needs to be evaluated. In this study, a logistic regression model was developed to predict the likelihood of these proteins to bind with drug-like molecules, based on comparisons with known protein structures that can bind to ligands. This method started with 23 previously identified proteins, leading to the identification of 8 proteins that have high potential for being druggable. This finding suggests that these proteins could be potential candidates for drug targets.

Technical Abstract: Prior studies have identified key proteins for stress response, virulence, and antimicrobial resistance and their interaction for Listeria monocytogenes. These proteins are identified to play a functional role in these processes and serve as potential targets for new methods to control L. monocytogenes. However, additional analysis is required to assess their druggability. In this work, a logistic regression model was developed using reference proteins to assess their druggability by determining if ligands can bind to the protein structures. The druggability analysis method was used to analyze 23 key proteins for L. monocytogenes that have been identified in the literature. The following proteins are predicted to be high-potential druggable targets: groEL, flgK, flgL, flhB, fliG, fliH/fliI complex, inlA, mogR, and prfA. These results provide a starting point for further work to identify specific compounds that can dock to the druggable target proteins and experimental work to confirm they are effective targets.