Clinical Whole-Genome Sequencing Assay for Rapid <i>Mycobacterium tuberculosis</i> Complex First-Line Drug Susceptibility Testing and Phylogenetic Relatedness Analysis
The global rise of drug resistant tuberculosis has highlighted the need for improved diagnostic technologies that provide rapid and reliable drug resistance results. Here, we develop and validate a whole genome sequencing (WGS)-based test for identification of mycobacterium tuberculosis complex (MTB...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-10-01
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| Series: | Microorganisms |
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| Online Access: | https://www.mdpi.com/2076-2607/11/10/2538 |
| _version_ | 1797572859408678912 |
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| author | Bennett Shaw Benjamin von Bredow Allison Tsan Omai Garner Shangxin Yang |
| author_facet | Bennett Shaw Benjamin von Bredow Allison Tsan Omai Garner Shangxin Yang |
| author_sort | Bennett Shaw |
| collection | DOAJ |
| description | The global rise of drug resistant tuberculosis has highlighted the need for improved diagnostic technologies that provide rapid and reliable drug resistance results. Here, we develop and validate a whole genome sequencing (WGS)-based test for identification of mycobacterium tuberculosis complex (MTB) drug resistance to rifampin, isoniazid, pyrazinamide, ethambutol, and streptomycin. Through comparative analysis of drug resistance results from WGS-based testing and phenotypic drug susceptibility testing (DST) of 38 clinical MTB isolates from patients receiving care in Los Angeles, CA, we found an overall concordance between methods of 97.4% with equivalent performance across culture media. Critically, prospective analysis of 11 isolates showed that WGS-based testing provides results an average of 36 days faster than phenotypic culture-based methods. We showcase the additional benefits of WGS data by investigating a suspected laboratory contamination event and using phylogenetic analysis to search for cryptic local transmission, finding no evidence of community spread amongst our patient population in the past six years. WGS-based testing for MTB drug resistance has the potential to greatly improve diagnosis of drug resistant MTB by accelerating turnaround time while maintaining accuracy and providing additional benefits for infection control, lab safety, and public health applications. |
| first_indexed | 2024-03-10T21:01:46Z |
| format | Article |
| id | doaj.art-90cf2e8fbb8342eb9d8f18d0aa0c8e57 |
| institution | Directory Open Access Journal |
| issn | 2076-2607 |
| language | English |
| last_indexed | 2024-03-10T21:01:46Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Microorganisms |
| spelling | doaj.art-90cf2e8fbb8342eb9d8f18d0aa0c8e572023-11-19T17:28:16ZengMDPI AGMicroorganisms2076-26072023-10-011110253810.3390/microorganisms11102538Clinical Whole-Genome Sequencing Assay for Rapid <i>Mycobacterium tuberculosis</i> Complex First-Line Drug Susceptibility Testing and Phylogenetic Relatedness AnalysisBennett Shaw0Benjamin von Bredow1Allison Tsan2Omai Garner3Shangxin Yang4Department of Pathology and Laboratory Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA 90095, USADepartment of Pathology and Laboratory Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA 90095, USADepartment of Pathology and Laboratory Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA 90095, USADepartment of Pathology and Laboratory Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA 90095, USADepartment of Pathology and Laboratory Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA 90095, USAThe global rise of drug resistant tuberculosis has highlighted the need for improved diagnostic technologies that provide rapid and reliable drug resistance results. Here, we develop and validate a whole genome sequencing (WGS)-based test for identification of mycobacterium tuberculosis complex (MTB) drug resistance to rifampin, isoniazid, pyrazinamide, ethambutol, and streptomycin. Through comparative analysis of drug resistance results from WGS-based testing and phenotypic drug susceptibility testing (DST) of 38 clinical MTB isolates from patients receiving care in Los Angeles, CA, we found an overall concordance between methods of 97.4% with equivalent performance across culture media. Critically, prospective analysis of 11 isolates showed that WGS-based testing provides results an average of 36 days faster than phenotypic culture-based methods. We showcase the additional benefits of WGS data by investigating a suspected laboratory contamination event and using phylogenetic analysis to search for cryptic local transmission, finding no evidence of community spread amongst our patient population in the past six years. WGS-based testing for MTB drug resistance has the potential to greatly improve diagnosis of drug resistant MTB by accelerating turnaround time while maintaining accuracy and providing additional benefits for infection control, lab safety, and public health applications.https://www.mdpi.com/2076-2607/11/10/2538whole-genome sequencing<i>Mycobacterium tuberculosis</i> complexdrug susceptibility testingphylogenetic relatedness analysisclinical evaluation |
| spellingShingle | Bennett Shaw Benjamin von Bredow Allison Tsan Omai Garner Shangxin Yang Clinical Whole-Genome Sequencing Assay for Rapid <i>Mycobacterium tuberculosis</i> Complex First-Line Drug Susceptibility Testing and Phylogenetic Relatedness Analysis Microorganisms whole-genome sequencing <i>Mycobacterium tuberculosis</i> complex drug susceptibility testing phylogenetic relatedness analysis clinical evaluation |
| title | Clinical Whole-Genome Sequencing Assay for Rapid <i>Mycobacterium tuberculosis</i> Complex First-Line Drug Susceptibility Testing and Phylogenetic Relatedness Analysis |
| title_full | Clinical Whole-Genome Sequencing Assay for Rapid <i>Mycobacterium tuberculosis</i> Complex First-Line Drug Susceptibility Testing and Phylogenetic Relatedness Analysis |
| title_fullStr | Clinical Whole-Genome Sequencing Assay for Rapid <i>Mycobacterium tuberculosis</i> Complex First-Line Drug Susceptibility Testing and Phylogenetic Relatedness Analysis |
| title_full_unstemmed | Clinical Whole-Genome Sequencing Assay for Rapid <i>Mycobacterium tuberculosis</i> Complex First-Line Drug Susceptibility Testing and Phylogenetic Relatedness Analysis |
| title_short | Clinical Whole-Genome Sequencing Assay for Rapid <i>Mycobacterium tuberculosis</i> Complex First-Line Drug Susceptibility Testing and Phylogenetic Relatedness Analysis |
| title_sort | clinical whole genome sequencing assay for rapid i mycobacterium tuberculosis i complex first line drug susceptibility testing and phylogenetic relatedness analysis |
| topic | whole-genome sequencing <i>Mycobacterium tuberculosis</i> complex drug susceptibility testing phylogenetic relatedness analysis clinical evaluation |
| url | https://www.mdpi.com/2076-2607/11/10/2538 |
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