BioModels

This model is a Chemprop neural network trained with a growth inhibition dataset. Authors screened ~7,500 molecules for those that inhibited the growth of A. baumannii in vitro. They discovered abaucin, an antibacterial compound with narrow-spectrum activity against A. baumannii.

Model Type: Predictive machine learning model.
Model Relevance: The model predicts the probability of growth inhibition of the bacteria A. Baumannii.
Model Encoded by: Miquel Duran-frigola (Ersilia)
Metadata Submitted in BioModels by: Zainab Ashimiyu-Abdusalam

Implementation of this model code by Ersilia is available here:
https://github.com/ersilia-os/eos3804

• Deep learning-guided discovery of an antibiotic targeting Acinetobacter baumannii.
• Gary Liu, Denise B Catacutan, Khushi Rathod, Kyle Swanson, Wengong Jin, Jody C Mohammed, Anush Chiappino-Pepe, Saad A Syed, Meghan Fragis, Kenneth Rachwalski, Jakob Magolan, Michael G Surette, Brian K Coombes, Tommi Jaakkola, Regina Barzilay, James J Collins, Jonathan M Stokes
• Nature chemical biology , 11/ 2023 , Volume 19 , Issue 11 , pages: 1342-1350 , PubMed ID: 37231267
Affiliation: Department of Biochemistry and Biomedical Sciences, Michael G. DeGroote Institute for Infectious Disease Research, David Braley Centre for Antibiotic Discovery, McMaster University, Hamilton, Ontario, Canada.
Abstract: Acinetobacter baumannii is a nosocomial Gram-negative pathogen that often displays multidrug resistance. Discovering new antibiotics against A. baumannii has proven challenging through conventional screening approaches. Fortunately, machine learning methods allow for the rapid exploration of chemical space, increasing the probability of discovering new antibacterial molecules. Here we screened ~7,500 molecules for those that inhibited the growth of A. baumannii in vitro. We trained a neural network with this growth inhibition dataset and performed in silico predictions for structurally new molecules with activity against A. baumannii. Through this approach, we discovered abaucin, an antibacterial compound with narrow-spectrum activity against A. baumannii. Further investigations revealed that abaucin perturbs lipoprotein trafficking through a mechanism involving LolE. Moreover, abaucin could control an A. baumannii infection in a mouse wound model. This work highlights the utility of machine learning in antibiotic discovery and describes a promising lead with targeted activity against a challenging Gram-negative pathogen.