Mass spectrometry and machine learning for the accurate diagnosis of benzylpenicillin and multidrug resistance of Staphylococcus aureus in bovine mastitis

Esener, Necati; Guerra, Alexandre Maciel; Giebel, Katharina; Lea, Daniel; Green, Martin J.; Bradley, Andrew J.; Dottorini, Tania

Abstract

Staphylococcus aureus is a serious human and animal pathogen threat exhibiting extraordinary capacity for acquiring new antibiotic resistance traits in the pathogen population worldwide.

The development of fast, affordable and effective diagnostic solutions capable of discriminating between antibiotic-resistant and susceptible S. aureus strains would be of huge benefit for effective disease detection and treatment. Here we develop a diagnostics solution that uses Matrix-Assisted Laser Desorption/Ionisation–Time of Flight Mass Spectrometry (MALDI-TOF) and machine learning, to identify signature profiles of antibiotic resistance to either multidrug or benzylpenicillin in S. aureus isolates. Using ten different supervised learning techniques, we have analysed a set of 82 S. aureus isolates collected from 67 cows diagnosed with bovine mastitis across 24 farms. For the multidrug phenotyping analysis, LDA, linear SVM, RBF SVM, logistic regression, naïve Bayes, MLP neural network and QDA had Cohen’s kappa values over 85.00%. For the benzylpenicillin phenotyping analysis, RBF SVM, MLP neural network, naïve Bayes, logistic regression, linear SVM, QDA, LDA, and random forests had Cohen’s kappa values over 85.00%. For the benzylpenicillin the diagnostic systems achieved up to (mean result ± standard deviation over 30 runs on the test set): accuracy = 97.54% ± 1.91%, sensitivity = 99.93% ± 0.25%, specificity = 95.04% ± 3.83%, and Cohen’s kappa = 95.04% ± 3.83%. Moreover, the diagnostic platform complemented by a protein-protein network and 3D structural protein information framework allowed the identification of five molecular determinants underlying the susceptible and resistant profiles. Four proteins were able to classify multidrug-resistant and susceptible strains with 96.81% ± 0.43% accuracy. Five proteins, including the previous four, were able to classify benzylpenicillin resistant and susceptible strains with 97.54% ± 1.91% accuracy. Our approach may open up new avenues for the development of a fast, affordable and effective day-to-day diagnostic solution, which would offer new opportunities for targeting resistant bacteria.

Citation

Esener, N., Guerra, A. M., Giebel, K., Lea, D., Green, M. J., Bradley, A. J., & Dottorini, T. (2021). Mass spectrometry and machine learning for the accurate diagnosis of benzylpenicillin and multidrug resistance of Staphylococcus aureus in bovine mastitis. PLoS Computational Biology, 17(6), Article e1009108. https://doi.org/10.1371/journal.pcbi.1009108

• Journal Article Type: Article
• Acceptance Date: May 20, 2021
• Online Publication Date: Jun 11, 2021
• Publication Date: Jun 11, 2021
• Deposit Date: Jun 3, 2021
• Publicly Available Date: Jun 3, 2021
• Journal: PLoS Computational Biology
• Print ISSN: 1553-734X
• Electronic ISSN: 1553-7358
• Publisher: Public Library of Science
• Peer Reviewed: Peer Reviewed
• Volume: 17
• Issue: 6
• Article Number: e1009108
• DOI: https://doi.org/10.1371/journal.pcbi.1009108
• Keywords: Ecology; Modelling and Simulation; Computational Theory and Mathematics; Genetics; Ecology, Evolution, Behavior and Systematics; Molecular Biology; Cellular and Molecular Neuroscience
• Public URL: https://nottingham-repository.worktribe.com/output/5623884
• Publisher URL: https://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1009108