Nanomotion technology in combination with machine learning: a new approach for a rapid antibiotic susceptibility test for Mycobacterium tuberculosis

Microbes Infect. 2023 Sep-Oct;25(7):105151. doi: 10.1016/j.micinf.2023.105151. Epub 2023 May 18.

Abstract

Nanomotion technology is a growth-independent approach that can be used to detect and record the vibrations of bacteria attached to cantilevers. We have developed a nanomotion-based antibiotic susceptibility test (AST) protocol for Mycobacterium tuberculosis (MTB). The protocol was used to predict strain phenotype towards isoniazid (INH) and rifampicin (RIF) using a leave-one-out cross-validation (LOOCV) and machine learning techniques. This MTB-nanomotion protocol takes 21 h, including cell suspension preparation, optimized bacterial attachment to functionalized cantilever, and nanomotion recording before and after antibiotic exposure. We applied this protocol to MTB isolates (n = 40) and were able to discriminate between susceptible and resistant strains for INH and RIF with a maximum sensitivity of 97.4% and 100%, respectively, and a maximum specificity of 100% for both antibiotics when considering each nanomotion recording to be a distinct experiment. Grouping recordings as triplicates based on source isolate improved sensitivity and specificity to 100% for both antibiotics. Nanomotion technology can potentially reduce time-to-result significantly compared to the days and weeks currently needed for current phenotypic ASTs for MTB. It can further be extended to other anti-TB drugs to help guide more effective TB treatment.

Keywords: Antibiotic-susceptibility test; Atomic force microscopy; Machine learning; Multi-drug resistant tuberculosis; Mycobacterium tuberculosis; Nanomotion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antitubercular Agents / pharmacology
  • Antitubercular Agents / therapeutic use
  • Drug Resistance, Multiple, Bacterial / genetics
  • Humans
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis*
  • Rifampin / pharmacology
  • Tuberculosis, Multidrug-Resistant* / diagnosis
  • Tuberculosis, Multidrug-Resistant* / drug therapy
  • Tuberculosis, Multidrug-Resistant* / microbiology

Substances

  • Antitubercular Agents
  • Rifampin