Quantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of resistance and susceptibility in a target gene approach
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Published:2024-01-12
Issue:1
Volume:15
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
, Barilar Ivan, Battaglia Simone, Borroni Emanuele, Brandao Angela Pires, Brankin Alice, Cabibbe Andrea Maurizio, Carter JoshuaORCID, Chetty Darren, Cirillo Daniela Maria, Claxton Pauline, Clifton David A., Cohen Ted, Coronel Jorge, Crook Derrick W., Dreyer Viola, Earle Sarah G., Escuyer Vincent, Ferrazoli Lucilaine, Fowler Philip W., Gao George Fu, Gardy Jennifer, Gharbia Saheer, Ghisi Kelen Teixeira, Ghodousi Arash, Gibertoni Cruz Ana Luíza, Grandjean Louis, Grazian Clara, Groenheit Ramona, Guthrie Jennifer L., He Wencong, Hoffmann Harald, Hoosdally Sarah J., Hunt Martin, Iqbal Zamin, Ismail Nazir Ahmed, Jarrett Lisa, Joseph Lavania, Jou Ruwen, Kambli Priti, Khot Rukhsar, Knaggs Jeff, Koch Anastasia, Kohlerschmidt Donna, Kouchaki Samaneh, Lachapelle Alexander S., Lalvani Ajit, Lapierre Simon Grandjean, Laurenson Ian F., Letcher Brice, Lin Wan-Hsuan, Liu Chunfa, Liu Dongxin, Malone Kerri M., Mandal Ayan, Mansjö Mikael, Calisto Matias Daniela Vicente Lucena, Meintjes Graeme, de Freitas Mendes Flávia, Merker Matthias, Mihalic Marina, Millard James, Miotto Paolo, Mistry Nerges, Moore David, Musser Kimberlee A., Ngcamu Dumisani, Nhung Hoang Ngoc, Niemann Stefan, Nilgiriwala Kayzad Soli, Nimmo Camus, O’Donnell Max, Okozi Nana, Oliveira Rosangela Siqueira, Omar Shaheed Vally, Paton Nicholas, Peto Timothy E. A., Pinhata Juliana Maira Watanabe, Plesnik Sara, Puyen Zully M., Rabodoarivelo Marie Sylvianne, Rakotosamimanana Niaina, Rancoita Paola M. V., Rathod Priti, Robinson Esther Rhiannon, Rodger Gillian, Rodrigues Camilla, Rodwell Timothy C., Roohi Aysha, Santos-Lazaro David, Shah Sanchi, Smith Grace, Kohl Thomas Andreas, Solano Walter, Spitaleri Andrea, Steyn Adrie J. C., Supply Philip, Surve Utkarsha, Tahseen Sabira, Thuong Nguyen Thuy Thuong, Thwaites Guy, Todt Katharina, Trovato Alberto, Utpatel Christian, Van Rie Annelies, Vijay Srinivasan, Walker A. Sarah, Walker Timothy M., Warren Robin, Werngren Jim, Wijkander Maria, Wilkinson Robert J., Wilson Daniel J., Wintringer Penelope, Xiao Yu-Xin, Yang Yang, Yanlin Zhao, Yao Shen-Yuan, Zhu Baoli
Abstract
AbstractThe World Health Organization has a goal of universal drug susceptibility testing for patients with tuberculosis. However, molecular diagnostics to date have focused largely on first-line drugs and predicting susceptibilities in a binary manner (classifying strains as either susceptible or resistant). Here, we used a multivariable linear mixed model alongside whole genome sequencing and a quantitative microtiter plate assay to relate genomic mutations to minimum inhibitory concentration (MIC) in 15,211 Mycobacterium tuberculosis clinical isolates from 23 countries across five continents. We identified 492 unique MIC-elevating variants across 13 drugs, as well as 91 mutations likely linked to hypersensitivity. Our results advance genetics-based diagnostics for tuberculosis and serve as a curated training/testing dataset for development of drug resistance prediction algorithms.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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