Understanding and predicting ciprofloxacin minimum inhibitory concentration in Escherichia coli with machine learning.

Journal: Scientific reports
PMID:

Abstract

It is important that antibiotics prescriptions are based on antimicrobial susceptibility data to ensure effective treatment outcomes. The increasing availability of next-generation sequencing, bacterial whole genome sequencing (WGS) can facilitate a more reliable and faster alternative to traditional phenotyping for the detection and surveillance of AMR. This work proposes a machine learning approach that can predict the minimum inhibitory concentration (MIC) for a given antibiotic, here ciprofloxacin, on the basis of both genome-wide mutation profiles and profiles of acquired antimicrobial resistance genes. We analysed 704 Escherichia coli genomes combined with their respective MIC measurements for ciprofloxacin originating from different countries. The four most important predictors found by the model, mutations in gyrA residues Ser83 and Asp87, a mutation in parC residue Ser80 and presence of the qnrS1 gene, have been experimentally validated before. Using only these four predictors in a linear regression model, 65% and 93% of the test samples' MIC were correctly predicted within a two- and a four-fold dilution range, respectively. The presented work does not treat machine learning as a black box model concept, but also identifies the genomic features that determine susceptibility. The recent progress in WGS technology in combination with machine learning analysis approaches indicates that in the near future WGS of bacteria might become cheaper and faster than a MIC measurement.

Authors

  • Bálint Ármin Pataki
    Department of Physics of Complex Systems, ELTE Eötvös Loránd University, Budapest, Hungary. patbaa@caesar.elte.hu.
  • Sébastien Matamoros
    Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
  • Boas C L van der Putten
    Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.
  • Daniel Remondini
    Department of Physics and Astronomy (DIFA), University of Bologna, Bologna, Italy.
  • Enrico Giampieri
    Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.
  • Derya Aytan-Aktug
    National Food Institute, Technical University of Denmark, Lyngby, Denmark.
  • Rene S Hendriksen
    Division for Epidemiology and Microbial Genomics, National Food Institute, Technical University of Denmark, Kongens Lyngby, Denmark.
  • Ole Lund
    Department of Bioinformatics, Technical University of Denmark, Lyngby, Denmark.
  • István Csabai
    Department of Physics of Complex Systems, Eötvös Loránd University, Budapest, Hungary.
  • Constance Schultsz
    Department of Medical Microbiology, Amsterdam UMC, University of Amsterdam, Amsterdam, The Netherlands.