Whole-Genome Sequencing for Drug Resistance Profile Prediction in Mycobacterium tuberculosis

被引:59
作者
Gygli, Sebastian M. [1 ,2 ]
Keller, Peter M. [3 ,12 ]
Ballif, Marie [5 ]
Blochliger, Nicolas [3 ]
Homke, Rico [3 ,4 ]
Reinhard, Miriam [1 ,2 ]
Loiseau, Chloe [1 ,2 ]
Ritter, Claudia [3 ,4 ]
Sander, Peter [3 ,4 ]
Borrell, Sonia [1 ,2 ]
Collantes Loo, Jimena [11 ]
Avihingsanon, Anchalee [6 ,7 ]
Gnokoro, Joachim [8 ]
Yotebieng, Marcel [9 ]
Egger, Matthias [5 ,10 ]
Gagneux, Sebastien [1 ,2 ]
Bottger, Erik C. [3 ,4 ]
机构
[1] Swiss Trop & Publ Hlth Inst, Basel, Switzerland
[2] Univ Basel, Basel, Switzerland
[3] Univ Zurich, Inst Med Microbiol, Zurich, Switzerland
[4] Univ Zurich, Natl Ctr Mycobacteria, Zurich, Switzerland
[5] Univ Bern, Inst Social & Prevent Med, Bern, Switzerland
[6] HIV NAT Thai Red Cross AIDS Res Ctr, Bangkok, Thailand
[7] Chulalongkorn Univ, Fac Med, Dept Med, TB Res Unit, Bangkok, Thailand
[8] Ctr Prise Charge Rech & Format, Abidjan, Cote Ivoire
[9] Ohio State Univ, Coll Publ Hlth, Columbus, OH 43210 USA
[10] Univ Cape Town, Ctr Infect Dis Epidemiol & Res, Cape Town, South Africa
[11] Univ Peruana Cayetano Heredia, Inst Med Trop Alexander von Humboldt, Lima, Peru
[12] Univ Bern, Inst Infect Dis, Bern, Switzerland
基金
瑞士国家科学基金会; 欧洲研究理事会; 美国国家卫生研究院;
关键词
drug resistance; drug resistance level prediction; Mycobacterium tuberculosis; quantitative phenotypic drug susceptibility testing; whole-genome sequencing; LINE PROBE ASSAYS; ANTIBIOTIC-RESISTANCE; SUSCEPTIBILITY; MUTATIONS; EVOLUTION; DETERMINANTS; TRANSMISSION; ETHAMBUTOL; RIFAMPIN;
D O I
10.1128/AAC.02175-18
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Whole-genome sequencing allows rapid detection of drug-resistant Mycobacterium tuberculosis isolates. However, the availability of high-quality data linking quantitative phenotypic drug susceptibility testing (DST) and genomic data have thus far been limited. We determined drug resistance profiles of 176 genetically diverse clinical M. tuberculosis isolates from the Democratic Republic of the Congo, Ivory Coast, Peru, Thailand, and Switzerland by quantitative phenotypic DST for 11 antituberculous drugs using the BD Bactec MGIT 960 system and 7H10 agar dilution to generate a cross-validated phenotypic DST readout. We compared DST results with predicted drug resistance profiles inferred by whole-genome sequencing. Classification of strains by the two phenotypic DST methods into resistotype/wild-type populations was concordant in 73 to 99% of cases, depending on the drug. Our data suggest that the established critical concentration (5 mg/liter) for ethambutol resistance (MGIT 960 system) is too high and misclassifies strains as susceptible, unlike 7H10 agar dilution. Increased minimal inhibitory concentrations were explained by mutations identified by whole-genome sequencing. Using whole-genome sequences, we were able to predict quantitative drug resistance levels for the majority of drug resistance mutations. Predicting quantitative levels of drug resistance by whole-genome sequencing was partially limited due to incompletely understood drug resistance mechanisms. The overall sensitivity and specificity of whole-genome-based DST were 86.8% and 94.5%, respectively. Despite some limitations, whole-genome sequencing has the potential to infer resistance profiles without the need for time-consuming phenotypic methods.
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页数:13
相关论文
共 49 条
[1]   Prediction of Susceptibility to First-Line Tuberculosis Drugs by DNA Sequencing [J].
Allix-Beguec, Caroline ;
Arandjelovic, Irena ;
Bi, Lijun ;
Beckert, Patrick ;
Bonnet, Maryline ;
Bradley, Phelim ;
Cabibbe, Andrea M. ;
Cancino-Munoz, Irving ;
Caulfield, Mark J. ;
Chaiprasert, Angkana ;
Cirillo, Daniela M. ;
Clifton, David ;
Comas, Inaki ;
Crook, Derrick W. ;
De Filippo, Maria R. ;
de Neeling, Han ;
Diel, Roland ;
Drobniewski, Francis A. ;
Faksri, Kiatichai ;
Farhat, Maha R. ;
Fleming, Joy ;
Fowler, Philip ;
Fowler, Tom A. ;
Gao, Qian ;
Gardy, Jennifer ;
Gascoyne-Binzi, Deborah ;
Gibertoni-Cruz, Ana-Luiza ;
Gil-Brusola, Ana ;
Golubchik, Tanya ;
Gonzalo, Ximena ;
Grandjean, Louis ;
He, Guangxue ;
Guthrie, Jennifer L. ;
Hoosdally, Sarah ;
Hunt, Martin ;
Iqbal, Zamin ;
Ismail, Nazir ;
Johnston, James ;
Khanzada, Faisal M. ;
Khor, Chiea C. ;
Kohl, Thomas A. ;
Kong, Clare ;
Lipworth, Sam ;
Liu, Qingyun ;
Maphalala, Gugu ;
Martinez, Elena ;
Mathys, Vanessa ;
Merker, Matthias ;
Miotto, Paolo ;
Mistry, Nerges .
NEW ENGLAND JOURNAL OF MEDICINE, 2018, 379 (15) :1403-1415
[2]   Challenging a dogma: antimicrobial susceptibility testing breakpoints for Mycobacterium tuberculosis [J].
Angeby, Kristian ;
Jureen, Pontus ;
Kahlmeter, Gunnar ;
Hoffner, Sven E. ;
Schon, Thomas .
BULLETIN OF THE WORLD HEALTH ORGANIZATION, 2012, 90 (09) :693-698
[3]  
[Anonymous], 2014, COMPANION HDB WHO GU
[4]  
[Anonymous], 2018, Technical report on critical concentrations for drug susceptibility testing of medicines used in the treatment of drug-resistant tuberculosis
[5]  
[Anonymous], 2010, TREATM TUB GUID
[6]  
[Anonymous], 2013, Automated real-time nucleic acid amplification technology for rapid and simultaneous detection of tuberculosis and rifampicin resistance: Xpert MTB/RIF assay for the diagnosis of pulmonary and extrapulmonary TB in adults and children: policy update
[7]   Rifabutin and rifampin resistance levels and associated rpoB mutations in clinical isolates of Mycobacterium tuberculosis complex [J].
Berrada, Zenda L. ;
Lin, Shou-Yean Grace ;
Rodwell, Timothy C. ;
Duylinh Nguyen ;
Schecter, Gisela F. ;
Pham, Lucy ;
Janda, J. Michael ;
Elmaraachli, Wael ;
Catanzaro, Antonino ;
Desmond, Edward .
DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE, 2016, 85 (02) :177-181
[8]   STATISTICAL METHODS FOR ASSESSING AGREEMENT BETWEEN TWO METHODS OF CLINICAL MEASUREMENT [J].
BLAND, JM ;
ALTMAN, DG .
LANCET, 1986, 1 (8476) :307-310
[9]   Acquired Resistance to Bedaquiline and Delamanid in Therapy for Tuberculosis [J].
Bloemberg, Guido V. ;
Gagneux, Sebastien ;
Boettger, Erik C. .
NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (20) :1986-1988
[10]   The ins and outs of Mycobacterium tuberculosis drug susceptibility testing [J].
Boettger, E. C. .
CLINICAL MICROBIOLOGY AND INFECTION, 2011, 17 (08) :1128-1134