Quantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of resistance and susceptibility in a target gene approach

Ivan Barilar; Simone Battaglia; Emanuele Borroni; Angela Pires Brandao; Alice Brankin; Andrea Maurizio Cabibbe; Joshua Carter; Darren Chetty; Daniela Maria Cirillo; Pauline Claxton; David Clifton; Ted Cohen; Jorge Coronel; Derrick Crook; Viola Dreyer; Sarah Earle; Vincent Escuyer; Lucilaine Ferrazoli; Philip Fowler; George Fu Gao; Jennifer Gardy; Saheer Gharbia; Kelen Teixeira Ghisi; Arash Ghodousi; Ana Luíza Gibertoni Cruz; Louis Grandjean; Clara Grazian; Ramona Groenheit; Jennifer Guthrie; Wencong He; Harald Hoffmann; Sarah Hoosdally; Martin Hunt; Zamin Iqbal; Nazir Ahmed Ismail; Lisa Jarrett; Lavania Joseph; Ruwen Jou; Priti Kambli; Rukhsar Khot; Jeff Knaggs; Anastasia Koch; Donna Kohlerschmidt; Samaneh Kouchaki; Alexander Lachapelle; Ajit Lalvani; Simon Grandjean Lapierre; Ian Laurenson; Brice Letcher; Wan-Hsuan Lin; Chunfa Liu; Dongxin Liu; Kerri Malone; Ayan Mandal; Mikael Mansjö; Daniela Vicente Lucena Calisto Matias; Graeme Meintjes; Flávia de Freitas Mendes; Matthias Merker; Marina Mihalic; James Millard; Paolo Miotto; Nerges Mistry; David Moore; Kimberlee Musser; Dumisani Ngcamu; Hoang Ngoc Nhung; Stefan Niemann; Kayzad Soli Nilgiriwala; Camus Nimmo; Max O’donnell; Nana Okozi; Rosangela Siqueira Oliveira; Shaheed Vally Omar; Nicholas Paton; Timothy Peto; Juliana Maira Watanabe Pinhata; Sara Plesnik; Zully Puyen; Marie Sylvianne Rabodoarivelo; Niaina Rakotosamimanana; Paola Rancoita; Priti Rathod; Esther Rhiannon Robinson; Gillian Rodger; Camilla Rodrigues; Timothy Rodwell; Aysha Roohi; David Santos-Lazaro; Sanchi Shah; Grace Smith; Thomas Andreas Kohl; Walter Solano; Andrea Spitaleri; Adrie Steyn; Philip Supply; Utkarsha Surve; Sabira Tahseen; Nguyen Thuy Thuong Thuong; Guy Thwaites; Katharina Todt; Alberto Trovato; Christian Utpatel; Annelies van Rie; Srinivasan Vijay; A. Sarah Walker; Timothy Walker; Robin Warren; Jim Werngren; Maria Wijkander; Robert Wilkinson; Daniel Wilson; Penelope Wintringer; Yu-Xin Xiao; Yang Yang; Zhao Yanlin; Shen-Yuan Yao; Baoli Zhu

doi:10.1038/s41467-023-44325-5

Journal Articles Nature Communications Year : 2024

Quantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of resistance and susceptibility in a target gene approach

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Ivan Barilar

Function : Author

Simone Battaglia

Function : Author

Emanuele Borroni

Function : Author

Angela Pires Brandao

Function : Author

Alice Brankin

Function : Author

Andrea Maurizio Cabibbe

Function : Author

Joshua Carter

Function : Author
PersonId : 1354569
ORCID : 0000-0002-9194-7966

Darren Chetty

Function : Author

Daniela Maria Cirillo

Function : Author

Pauline Claxton

Function : Author

David Clifton

Function : Author

Ted Cohen

Function : Author

Jorge Coronel

Function : Author

Derrick Crook

Function : Author

Viola Dreyer

Function : Author

Sarah Earle

Function : Author

Vincent Escuyer

Function : Author

Lucilaine Ferrazoli

Function : Author

Philip Fowler

Function : Author

George Fu Gao

Function : Author

Jennifer Gardy

Function : Author

Saheer Gharbia

Function : Author

Kelen Teixeira Ghisi

Function : Author

Arash Ghodousi

Function : Author

Ana Luíza Gibertoni Cruz

Function : Author

Louis Grandjean

Function : Author

Clara Grazian

Function : Author

Ramona Groenheit

Function : Author

Jennifer Guthrie

Function : Author

Wencong He

Function : Author

Harald Hoffmann

Function : Author

Sarah Hoosdally

Function : Author

Martin Hunt

Function : Author

Zamin Iqbal

Function : Author

Nazir Ahmed Ismail

Function : Author

Lisa Jarrett

Function : Author

Lavania Joseph

Function : Author

Ruwen Jou

Function : Author

Priti Kambli

Function : Author

Rukhsar Khot

Function : Author

Jeff Knaggs

Function : Author

Anastasia Koch

Function : Author

Donna Kohlerschmidt

Function : Author

Samaneh Kouchaki

Function : Author

Alexander Lachapelle

Function : Author

Ajit Lalvani

Function : Author

Simon Grandjean Lapierre

Function : Author

Ian Laurenson

Function : Author

Brice Letcher

Function : Author

Wan-Hsuan Lin

Function : Author

Chunfa Liu

Function : Author

Dongxin Liu

Function : Author

Kerri Malone

Function : Author

Ayan Mandal

Function : Author

Mikael Mansjö

Function : Author

Daniela Vicente Lucena Calisto Matias

Function : Author

Graeme Meintjes

Function : Author

Flávia de Freitas Mendes

Function : Author

Matthias Merker

Function : Author

Marina Mihalic

Function : Author

James Millard

Function : Author

Paolo Miotto

Function : Author

Nerges Mistry

Function : Author

David Moore

Function : Author

Kimberlee Musser

Function : Author

Dumisani Ngcamu

Function : Author

Hoang Ngoc Nhung

Function : Author

Stefan Niemann

Function : Author

Kayzad Soli Nilgiriwala

Function : Author

Camus Nimmo

Function : Author

Max O’donnell

Function : Author

Nana Okozi

Function : Author

Rosangela Siqueira Oliveira

Function : Author

Shaheed Vally Omar

Function : Author

Nicholas Paton

Function : Author

Timothy Peto

Function : Author

Juliana Maira Watanabe Pinhata

Function : Author

Sara Plesnik

Function : Author

Zully Puyen

Function : Author

Marie Sylvianne Rabodoarivelo

Function : Author

Niaina Rakotosamimanana

Function : Author

Paola Rancoita

Function : Author

Priti Rathod

Function : Author

Esther Rhiannon Robinson

Function : Author

Gillian Rodger

Function : Author

Camilla Rodrigues

Function : Author

Timothy Rodwell

Function : Author

Aysha Roohi

Function : Author

David Santos-Lazaro

Function : Author

Sanchi Shah

Function : Author

Grace Smith

Function : Author

Thomas Andreas Kohl

Function : Author

Walter Solano

Function : Author

Andrea Spitaleri

Function : Author

Adrie Steyn

Function : Author

Philip Supply

Function : Author
PersonId : 741536
IdHAL : philip-supply
ORCID : 0000-0003-3690-3853
IdRef : 077084977

Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204

Utkarsha Surve

Function : Author

Sabira Tahseen

Function : Author

Nguyen Thuy Thuong Thuong

Function : Author

Guy Thwaites

Function : Author

Katharina Todt

Function : Author

Alberto Trovato

Function : Author

Christian Utpatel

Function : Author

Annelies van Rie

Function : Author

Srinivasan Vijay

Function : Author

A. Sarah Walker

Function : Author

Timothy Walker

Function : Author

Robin Warren

Function : Author

Jim Werngren

Function : Author

Maria Wijkander

Function : Author

Robert Wilkinson

Function : Author

Daniel Wilson

Function : Author

Penelope Wintringer

Function : Author

Yu-Xin Xiao

Function : Author

Yang Yang

Function : Author

Zhao Yanlin

Function : Author

Shen-Yuan Yao

Function : Author

Baoli Zhu

Function : Author

Abstract

The 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.

Domains

Bacteriology Genomics [q-bio.GN] Pharmacology

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s41467-023-44325-5.pdf (2.75 Mo)

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Philip Supply : Connect in order to contact the contributor

https://hal.science/hal-04467428

Submitted on : Wednesday, September 4, 2024-1:46:06 PM

Last modification on : Wednesday, September 4, 2024-2:04:06 PM

Dates and versions

hal-04467428 , version 1 (04-09-2024)

Identifiers

HAL Id : hal-04467428 , version 1
DOI : 10.1038/s41467-023-44325-5

Cite

Ivan Barilar, Simone Battaglia, Emanuele Borroni, Angela Pires Brandao, Alice Brankin, et al.. Quantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of resistance and susceptibility in a target gene approach. Nature Communications, 2024, 15 (1), pp.488. ⟨10.1038/s41467-023-44325-5⟩. ⟨hal-04467428⟩

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Quantitative measurement of antibiotic resistance in Mycobacterium tuberculosis reveals genetic determinants of resistance and susceptibility in a target gene approach

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