Rapid inference of antibiotic resistance and susceptibility by genomic neighbour typing.
Karel Bå IndaAlanna CallendrelloKevin C MaDerek R MacFaddenThemoula CharalampousRobyn S LeeLauren CowleyCrista B WadsworthYonatan Hagai GradGregory KucherovJustin O'GradyMichael H BaymWilliam P HanagePublished in: Nature microbiology (2020)
Surveillance of drug-resistant bacteria is essential for healthcare providers to deliver effective empirical antibiotic therapy. However, traditional molecular epidemiology does not typically occur on a timescale that could affect patient treatment and outcomes. Here, we present a method called 'genomic neighbour typing' for inferring the phenotype of a bacterial sample by identifying its closest relatives in a database of genomes with metadata. We show that this technique can infer antibiotic susceptibility and resistance for both Streptococcus pneumoniae and Neisseria gonorrhoeae. We implemented this with rapid k-mer matching, which, when used on Oxford Nanopore MinION data, can run in real time. This resulted in the determination of resistance within 10 min (91% sensitivity and 100% specificity for S. pneumoniae and 81% sensitivity and 100% specificity for N. gonorrhoeae from isolates with a representative database) of starting sequencing, and within 4 h of sample collection (75% sensitivity and 100% specificity for S. pneumoniae) for clinical metagenomic sputum samples. This flexible approach has wide application for pathogen surveillance and may be used to greatly accelerate appropriate empirical antibiotic treatment.
Keyphrases
- drug resistant
- healthcare
- public health
- single cell
- mycobacterium tuberculosis
- cystic fibrosis
- copy number
- type diabetes
- dna methylation
- case report
- acinetobacter baumannii
- metabolic syndrome
- high resolution
- structural basis
- machine learning
- combination therapy
- bone marrow
- big data
- single molecule
- cell therapy
- adipose tissue
- cross sectional
- solid phase extraction
- glycemic control
- affordable care act
- artificial intelligence
- anaerobic digestion