title: Unified QSAR approach to antimicrobials. Part 2: predicting activity against more than 90 different species in order to halt antibacterial resistance.
abstract: There are many different kinds of pathogenic bacteria species with very different susceptibility profiles to different antibacterial drugs. One limitation of QSAR models is that they consider the biological activity of drugs against only one species of bacteria. In a previous paper, we developed a unified Markov model to describe the biological activity of different drugs tested in the literature against some antimicrobial species. Consequently, predicting the probability with which a drug is active against different species of bacteria with a single unified model is a goal of major importance. The work described here develops the unified Markov model to describe the biological activity of more than 70 drugs from the literature tested against 96 species of bacteria. We applied linear discriminant analysis (LDA) to classify drugs as active or inactive against the different tested bacterial species. The model correctly classified 199 out of 237 active compounds (83.9%) and 168 out of 200 inactive compounds (84%). Overall training predictability was 84% (367 out of 437 cases). Validation of the model was carried out using an external predicting series, with the model classifying 202 out of 243 (i.e., 83.13%) of the compounds. In order to show how the model functions in practice, a virtual screening was carried out and the model recognized as active 84.5% (480 out of 568) antibacterial compounds not used in the training or predicting series. The current study is an attempt to calculate within a unified framework the probabilities of antibacterial action of drugs against many different species.
authors.affiliation: Department of Organic Chemistry and Institute of Industrial Pharmacy, Faculty of Pharmacy, University of Santiago de Compostela, 15782 Santiago, Spain.
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Prado-Prado
authors.forename: Humberto
authors.initials: H
authors.lastname: González-Díaz
authors.forename: Lourdes
authors.initials: L
authors.lastname: Santana
authors.forename: Eugenio
authors.initials: E
authors.lastname: Uriarte
mesh_terms: D000465:Algorithms; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000382:microbiology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D024881:Drug Resistance, Bacterial; D008390:Markov Chains; D015233:Models, Statistical; D011237:Predictive Value of Tests; D021281:Quantitative Structure-Activity Relationship; D012372:ROC Curve
chemical_list: D000900:Anti-Bacterial Agents