Rapid antibiotic-resistance predictions from genome sequence data for Staphylococcus aureus and Mycobacterium tuberculosis

被引：396

作者：

Bradley, Phelim ^{[1
]}

Gordon, N. Claire ^{[2
]}

Walker, Timothy M. ^{[2
]}

Dunn, Laura ^{[2
]}

Heys, Simon ^{[1
]}

Huang, Bill ^{[1
]}

Earle, Sarah ^{[2
]}

Pankhurst, Louise J. ^{[2
]}

Anson, Luke ^{[2
]}

de Cesare, Mariateresa ^{[1
]}

Piazza, Paolo ^{[1
]}

Votintseva, Antonina A. ^{[2
]}

Golubchik, Tanya ^{[2
]}

Wilson, Daniel J. ^{[1
,2
]}

Wyllie, David H. ^{[2
]}

Diel, Roland ^{[3
]}

Niemann, Stefan ^{[4
,5
]}

Feuerriegel, Silke ^{[4
,5
]}

Kohl, Thomas A. ^{[4
]}

Ismail, Nazir ^{[6
,7
]}

Omar, Shaheed V. ^{[6
]}

Smith, E. Grace ^{[8
]}

Buck, David ^{[1
]}

McVean, Gil ^{[1
]}

Walker, A. Sarah ^{[2
,9
]}

Peto, Tim E. A. ^{[2
,9
]}

Crook, Derrick W. ^{[2
,9
]}

Iqbal, Zamin ^{[1
,10
]}

机构：

[1] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England

[2] Univ Oxford, Nuffield Dept Med, Oxford OX1 1NF, England

[3] Univ Med Hosp Schleswig Holstein, Inst Epidemiol, D-24105 Kiel, Germany

[4] Res Ctr Borstel, Mol & Expt Mycobacteriol, D-23845 Borstel, Germany

[5] German Ctr Infect Res, D-23845 Borstel, Germany

[6] Natl Inst Communicable Dis, Ctr TB, ZA-2131 Johannesburg, South Africa

[7] Univ Pretoria, Dept Med Microbiol, ZA-0001 Pretoria, South Africa

[8] PHE Publ Hlth Lab Birmingham Heartlands Hosp, Reg Ctr Mycobacteriol, Birmingham B9 5SS, W Midlands, England

[9] NIHR Natl Inst Hlth Res, Biomed Res Ctr, Oxford Biomed Res Ctr, Oxford OX3 7LE, England

[10] Publ Hlth England, Natl Infect Serv, London SE1 8UG, England

来源：

NATURE COMMUNICATIONS | 2015年 / 6卷

基金：

英国惠康基金; 英国医学研究理事会;

关键词：

DRUG-RESISTANCE; RPOB MUTATIONS; ANTIMICROBIAL RESISTANCE; RIFAMPIN RESISTANCE; MTBDRPLUS ASSAY; SUSCEPTIBILITY; PERFORMANCE; BLOOD; MICROBIOLOGY; SURVEILLANCE;

D O I：

10.1038/ncomms10063

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

The rise of antibiotic-resistant bacteria has led to an urgent need for rapid detection of drug resistance in clinical samples, and improvements in global surveillance. Here we show how de Bruijn graph representation of bacterial diversity can be used to identify species and resistance profiles of clinical isolates. We implement this method for Staphylococcus aureus and Mycobacterium tuberculosis in a software package ('Mykrobe predictor') that takes raw sequence data as input, and generates a clinician-friendly report within 3 minutes on a laptop. For S. aureus, the error rates of our method are comparable to gold-standard phenotypic methods, with sensitivity/specificity of 99.1%/99.6% across 12 antibiotics (using an independent validation set, n = 470). For M. tuberculosis, our method predicts resistance with sensitivity/specificity of 82.6%/98.5% (independent validation set, n = 1,609); sensitivity is lower here, probably because of limited understanding of the underlying genetic mechanisms. We give evidence that minor alleles improve detection of extremely drug-resistant strains, and demonstrate feasibility of the use of emerging single-molecule nanopore sequencing techniques for these purposes.

引用

页数：14

共 62 条

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