Inferring patient to patient transmission of Mycobacterium tuberculosis from whole genome sequencing data

BMC Infectious Diseases

Dick van Soolingen³  Julian Parkhill⁷  Stephen D Bentley⁷  Martien Borgdorff⁴  Roland J Siezen⁵  Sacha A F T van Hijum¹  Kristin Kremer⁶  Victor de Jager⁵  Jessica L de Beer⁶  Simon R Harris⁷  Henk van Deutekom²  Anita C Schürch⁸  Josephine M Bryant⁷ 

[1] NIZO food research, P.O. Box 206710 BA, Ede, The Netherlands;Department of tuberculosis control, Public Health Service, Amsterdam, The Netherlands;Department of Clinical Microbiology and department of Lung Disease, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands;Department of Clinical Epidemiology, Biostatistics, and Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands;Netherlands Bioinformatics Centre (NBIC), P.O. Box 91016500HB, Nijmegen, The Netherlands;RIVM, Tuberculosis Reference Laboratory, National Institute for Public Health and the Environment (RIVM), Centre for Infectious Disease Control, (CIb/LIS, pb 22), P.O. Box 13720 BA, Bilthoven, The Netherlands;Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SA, UK;Department of Virology, Erasmus Medical Center, Rotterdam, The Netherlands

关键词: Epidemiology;    Transmission;    Whole genome sequencing;    Molecular clock;    Mycobacterium tuberculosis;   

Others  :  1171013
DOI  :  10.1186/1471-2334-13-110

 received in 2013-01-31, accepted in 2013-02-19,  发布年份 2013

【 摘 要 】

Background

Mycobacterium tuberculosis is characterised by limited genomic diversity, which makes the application of whole genome sequencing particularly attractive for clinical and epidemiological investigation. However, in order to confidently infer transmission events, an accurate knowledge of the rate of change in the genome over relevant timescales is required.

Methods

We attempted to estimate a molecular clock by sequencing 199 isolates from epidemiologically linked tuberculosis cases, collected in the Netherlands spanning almost 16 years.

Results

Multiple analyses support an average mutation rate of ~0.3 SNPs per genome per year. However, all analyses revealed a very high degree of variation around this mean, making the confirmation of links proposed by epidemiology, and inference of novel links, difficult. Despite this, in some cases, the phylogenetic context of other strains provided evidence supporting the confident exclusion of previously inferred epidemiological links.

Conclusions

This in-depth analysis of the molecular clock revealed that it is slow and variable over short time scales, which limits its usefulness in transmission studies. However, the superior resolution of whole genome sequencing can provide the phylogenetic context to allow the confident exclusion of possible transmission events previously inferred via traditional DNA fingerprinting techniques and epidemiological cluster investigation. Despite the slow generation of variation even at the whole genome level we conclude that the investigation of tuberculosis transmission will benefit greatly from routine whole genome sequencing.

【 授权许可】

   
2013 Bryant et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

Figure 5.

Figure 6.

Figure 7.

【 参考文献 】

• [1]WHO: Global tuberculosis report 2012. Geneva, Switzerland: World Health Organisation, WHO Press; 2012.
• [2]Van Soolingen D: Molecular epidemiology of tuberculosis and other mycobacterial infections: main methodologies and achievements. J Intern Med 2001, 249(1):1-26.
• [3]Supply P, Allix C, Lesjean S, Cardoso-Oelemann M, Rusch-Gerdes S, Willery E, Savine E, de Haas P, van Deutekom H, Roring S: Proposal for standardization of optimized mycobacterial interspersed repetitive unit-variable-number tandem repeat typing of mycobacterium tuberculosis. J Clin Microbiol 2006, 44(12):4498-4510.
• [4]de Beer JL, Kremer K, Kodmon C, Supply P, van Soolingen D: First worldwide proficiency study on variable-number tandem-repeat typing of Mycobacterium tuberculosis complex strains. J Clin Microbiol 2012, 50(3):662-669.
• [5]Niemann S, Koser CU, Gagneux S, Plinke C, Homolka S, Bignell H, Carter RJ, Cheetham RK, Cox A, Gormley NA: Genomic diversity among drug sensitive and multidrug resistant isolates of mycobacterium tuberculosis with identical DNA fingerprints. PLoS One 2009, 4(10):e7407.
• [6]Gardy JL, Johnston JC, Ho Sui SJ, Cook VJ, Shah L, Brodkin E, Rempel S, Moore R, Zhao Y, Holt R: Whole-genome sequencing and social-network analysis of a tuberculosis outbreak. N Engl J Med 2011, 364(8):730-739.
• [7]Schurch AC, Kremer K, Daviena O, Kiers A, Boeree MJ, Siezen RJ, van Soolingen D: High-resolution typing by integration of genome sequencing data in a large tuberculosis cluster. J Clin Microbiol 2010, 48(9):3403-3406.
• [8]Koser CU, Ellington MJ, Cartwright EJ, Gillespie SH, Brown NM, Farrington M, Holden MT, Dougan G, Bentley SD, Parkhill J: Routine use of microbial whole genome sequencing in diagnostic and public health microbiology. PLoS Pathog 2012, 8(8):e1002824.
• [9]Schurch AC, Kremer K, Kiers A, Daviena O, Boeree MJ, Siezen RJ, Smith NH, van Soolingen D: The tempo and mode of molecular evolution of mycobacterium tuberculosis at patient-to-patient scale. Infect Genet Evol 2010, 10(1):108-114.
• [10]Ford CB, Lin PL, Chase MR, Shah RR, Iartchouk O, Galagan J, Mohaideen N, Ioerger TR, Sacchettini JC, Lipsitch M: Use of whole genome sequencing to estimate the mutation rate of Mycobacterium tuberculosis during latent infection. Nat Genet 2011, 43(5):482-486.
• [11]Walker TM, Ip CLC, Harrell RH, Evans JT, Kapatai G, Dedicoat MJ, Eyre DW, Wilson DJ, Hawkey PM, Crook DW: Whole-genome sequencing to delineate mycobacterium tuberculosis outbreaks: a retrospective observational study. Lancet Infect Dis 2013, 13(2):137-146.
• [12]Veen J: Microepidemics of tuberculosis: the stone-in-the-pond principle. Tuber Lung Dis 1992, 73(2):73-76.
• [13]van Embden JD, Cave MD, Crawford JT, Dale JW, Eisenach KD, Gicquel B, Hermans P, Martin C, McAdam R, Shinnick TM: Strain identification of mycobacterium tuberculosis by DNA fingerprinting: recommendations for a standardized methodology. J Clin Microbiol 1993, 31(2):406-409.
• [14]Kamerbeek J, Schouls L, Kolk A, van Agterveld M, van Soolingen D, Kuijper S, Bunschoten A, Molhuizen H, Shaw R, Goyal M: Simultaneous detection and strain differentiation of mycobacterium tuberculosis for diagnosis and epidemiology. J Clin Microbiol 1997, 35(4):907-914.
• [15]Devaux I, Kremer K, Heersma H, Van Soolingen D: Clusters of multidrug-resistant mycobacterium tuberculosis cases, europe. Emerg Infect Dis 2009, 15(7):1052-1060.
• [16]Van Soolingen D, De Haas P, Kremer K: Restriction fragment length polymorphism typing of mycobacteria. In Mycobacterium tuberculosis protocols. 12th edition. Edited by Parish T, Stoker NG. Totowa NJ: Humana Press Inc; 2001:165-203.
• [17]Casali N, Nikolayevskyy V, Balabanova Y, Ignatyeva O, Kontsevaya I, Harris SR, Bentley SD, Parkhill J, Nejentsev S, Hoffner SE: Microevolution of extensively drug-resistant tuberculosis in Russia. Genome Res 2012, 22(4):735-745.
• [18]SMALT v0.5.8http://www.sanger.ac.uk/resources/software/smalt/ webcite
• [19]Li H, Handsaker B, Wysoker A, Fennell T, Ruan J, Homer N, Marth G, Abecasis G, Durbin R: The sequence alignment/Map format and SAMtools. Bioinformatics 2009, 25(16):2078-2079.
• [20]Stamatakis A: RAxML-VI-HPC: maximum likelihood-based phylogenetic analyses with thousands of taxa and mixed models. Bioinformatics 2006, 22(21):2688-2690.
• [21]Path-O-Genhttp://tree.bio.ed.ac.uk/software/pathogen/ webcite
• [22]Gagneux S, Small PM: Global phylogeography of mycobacterium tuberculosis and implications for tuberculosis product development. Lancet Infect Dis 2007, 7(5):328-337.
• [23]Ramaswamy S, Musser JM: Molecular genetic basis of antimicrobial agent resistance in mycobacterium tuberculosis: 1998 update. Tubercle and lung disease: the official journal of the International Union against Tuberculosis and Lung Disease 1998, 79(1):3-29.
• [24]Takiff HE, Salazar L, Guerrero C, Philipp W, Huang WM, Kreiswirth B, Cole ST, Jacobs WR Jr, Telenti A: Cloning and nucleotide sequence of Mycobacterium tuberculosis gyrA and gyrB genes and detection of quinolone resistance mutations. Antimicrob Agents Chemother 1994, 38(4):773-780.
• [25]Maus CE, Plikaytis BB, Shinnick TM: Molecular analysis of cross-resistance to capreomycin, kanamycin, amikacin, and viomycin in mycobacterium tuberculosis. Antimicrob Agents Chemother 2005, 49(8):3192-3197.
• [26]Heym B, Alzari PM, Honore N, Cole ST: Missense mutations in the catalase-peroxidase gene, katG, are associated with isoniazid resistance in mycobacterium tuberculosis. Mol Microbiol 1995, 15(2):235-245.
• [27]Sreevatsan S, Stockbauer KE, Pan X, Kreiswirth BN, Moghazeh SL, Jacobs WR Jr, Telenti A, Musser JM: Ethambutol resistance in mycobacterium tuberculosis: critical role of embB mutations. Antimicrob Agents Chemother 1997, 41(8):1677-1681.
• [28]Movahedzadeh F, Smith DA, Norman RA, Dinadayala P, Murray-Rust J, Russell DG, Kendall SL, Rison SC, McAlister MS, Bancroft GJ: The mycobacterium tuberculosis ino1 gene is essential for growth and virulence. Mol Microbiol 2004, 51(4):1003-1014.
• [29]Jiang X, Zhang W, Gao F, Huang Y, Lv C, Wang H: Comparison of the proteome of isoniazid-resistant and -susceptible strains of mycobacterium tuberculosis. Microbial drug resistance 2006, 12(4):231-238.
• [30]Namouchi A, Didelot X, Schock U, Gicquel B, Rocha EP: After the bottleneck: genome-wide diversification of the mycobacterium tuberculosis complex by mutation, recombination, and natural selection. Genome Res 2012, 22(4):721-734.
• [31]Croucher NJ, Harris SR, Fraser C, Quail MA, Burton J, van der Linden M, McGee L, von Gottberg A, Song JH, Ko KS: Rapid pneumococcal evolution in response to clinical interventions. Science 2011, 331(6016):430-434.
• [32]Comas I, Borrell S, Roetzer A, Rose G, Malla B, Kato-Maeda M, Galagan J, Niemann S, Gagneux S: Whole-genome sequencing of rifampicin-resistant mycobacterium tuberculosis strains identifies compensatory mutations in RNA polymerase genes. Nat Genet 2011, 44(1):106-110.
• [33]Brown T, Nikolayevskyy V, Velji P, Drobniewski F: Associations between mycobacterium tuberculosis strains and phenotypes. Emerg Infect Dis 2010, 16(2):272-280.
• [34]Krishnan N, Malaga W, Constant P, Caws M, Tran TH, Salmons J, Nguyen TN, Nguyen DB, Daffe M, Young DB: Mycobacterium tuberculosis lineage influences innate immune response and virulence and is associated with distinct cell envelope lipid profiles. PLoS One 2011, 6(9):e23870.
• [35]Sun G, Luo T, Yang C, Dong X, Li J, Zhu Y, Zheng H, Tian W, Wang S, 3rd Barry CE: Dynamic population changes in mycobacterium tuberculosis during acquisition and fixation of drug resistance in patients. J Infect Dis 2012, 206(11):1726-1733.
• [36]Tsolaki AG, Gagneux S, Pym AS, de la Salmoniere YO G, Kreiswirth BN, Van Soolingen D, Small PM: Genomic deletions classify the beijing/W strains as a distinct genetic lineage of mycobacterium tuberculosis. J Clin Microbiol 2005, 43(7):3185-3191.
• [37]Didelot X, Bowden R, Wilson DJ, Peto TE, Crook DW: Transforming clinical microbiology with bacterial genome sequencing. Nat Rev Genet 2012, 13(9):601-612.
• [38]Mutreja A, Kim DW, Thomson NR, Connor TR, Lee JH, Kariuki S, Croucher NJ, Choi SY, Harris SR, Lebens M: Evidence for several waves of global transmission in the seventh cholera pandemic. Nature 2011, 477(7365):462-465.
• [39]Harris SR, Feil EJ, Holden MT, Quail MA, Nickerson EK, Chantratita N, Gardete S, Tavares A, Day N, Lindsay JA: Evolution of MRSA during hospital transmission and intercontinental spread. Science 2010, 327(5964):469-474.