1887

Abstract

An outbreak of multi-drug resistant (MDR) tuberculosis (TB) has been reported on Daru Island, Papua New Guinea. Mycobacterium tuberculosis strains driving this outbreak and the temporal accrual of drug resistance mutations have not been described. Whole genome sequencing of 100 of 165 clinical isolates referred from Daru General Hospital to the Supranational reference laboratory, Brisbane, during 2012–2015 revealed that 95 belonged to a single modern Beijing sub-lineage strain. Molecular dating suggested acquisition of streptomycin and isoniazid resistance in the 1960s, with potentially enhanced virulence mediated by an mycP1 mutation. The Beijing sub-lineage strain demonstrated a high degree of co-resistance between isoniazid and ethionamide (80/95; 84.2 %) attributed to an inhA promoter mutation combined with inhA and ndh coding mutations. Multi-drug resistance, observed in 78/95 samples, emerged with the acquisition of a typical rpoB mutation together with a compensatory rpoC mutation in the 1980s. There was independent acquisition of fluoroquinolone and aminoglycoside resistance, and evidence of local transmission of extensively drug resistant (XDR) strains from 2009. These findings underline the importance of whole genome sequencing in informing an effective public health response to MDR/XDR TB.

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2018-01-04
2024-03-28
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References

  1. World Health Organization., Global Tuberculosis Programme Global tuberculosis control: WHO report. Geneva: Global Tuberculosis Programme; pp. 15
  2. Abubakar I, Zignol M, Falzon D, Raviglione M, Ditiu L et al. Drug-resistant tuberculosis: time for visionary political leadership. Lancet Infect Dis 2013; 13:529–539 [View Article][PubMed]
    [Google Scholar]
  3. Trauner A, Borrell S, Reither K, Gagneux S. Evolution of drug resistance in tuberculosis: recent progress and implications for diagnosis and therapy. Drugs 2014; 74:1063–1072 [View Article][PubMed]
    [Google Scholar]
  4. Zhang Y, Yew WW. Mechanisms of drug resistance in Mycobacterium tuberculosis: update 2015. Int J Tuberc Lung Dis 2015; 19:1276–1289 [View Article][PubMed]
    [Google Scholar]
  5. Ragonnet R, Trauer JM, Denholm JT, Marais BJ, McBryde ES. High rates of multidrug-resistant and rifampicin-resistant tuberculosis among re-treatment cases: where do they come from?. BMC Infect Dis 2017; 17:36 [View Article][PubMed]
    [Google Scholar]
  6. Casali N, Nikolayevskyy V, Balabanova Y, Harris SR, Ignatyeva O et al. Evolution and transmission of drug-resistant tuberculosis in a Russian population. Nat Genet 2014; 46:279–286 [View Article][PubMed]
    [Google Scholar]
  7. Comas I, Borrell S, Roetzer A, Rose G, Malla B et al. Whole-genome sequencing of rifampicin-resistant Mycobacterium tuberculosis strains identifies compensatory mutations in RNA polymerase genes. Nat Genet 2012; 44:106–110 [View Article][PubMed]
    [Google Scholar]
  8. Müller B, Chihota VN, Pillay M, Klopper M, Streicher EM et al. Programmatically selected multidrug-resistant strains drive the emergence of extensively drug-resistant tuberculosis in South Africa. PLoS One 2013; 8:e70919 [View Article][PubMed]
    [Google Scholar]
  9. Hanekom M, van der Spuy GD, Gey van Pittius NC, McEvoy CR, Hoek KG et al. Discordance between mycobacterial interspersed repetitive-unit-variable-number tandem-repeat typing and IS6110 restriction fragment length polymorphism genotyping for analysis of Mycobacterium tuberculosis Beijing strains in a setting of high incidence of tuberculosis. J Clin Microbiol 2008; 46:3338–3345 [View Article][PubMed]
    [Google Scholar]
  10. Comas I, Homolka S, Niemann S, Gagneux S. Genotyping of genetically monomorphic bacteria: DNA sequencing in Mycobacterium tuberculosis highlights the limitations of current methodologies. PLoS One 2009; 4:e7815 [View Article][PubMed]
    [Google Scholar]
  11. Gurjav U, Outhred AC, Jelfs P, McCallum N, Wang Q et al. Whole genome sequencing demonstrates limited transmission within identified Mycobacterium tuberculosis clusters in New South Wales, Australia. PLoS One 2016; 11:e0163612 [View Article][PubMed]
    [Google Scholar]
  12. Cohen KA, Abeel T, Manson McGuire A, Desjardins CA, Munsamy V et al. Evolution of extensively drug-resistant tuberculosis over four decades: whole genome sequencing and dating analysis of Mycobacterium tuberculosis isolates from KwaZulu-Natal. PLoS Med 2015; 12:e1001880 [View Article][PubMed]
    [Google Scholar]
  13. Eldholm V, Monteserin J, Rieux A, Lopez B, Sobkowiak B et al. Four decades of transmission of a multidrug-resistant Mycobacterium tuberculosis outbreak strain. Nat Commun 2015; 6:7119 [View Article][PubMed]
    [Google Scholar]
  14. Cross GB, Coles K, Nikpour M, Moore OA, Denholm J et al. TB incidence and characteristics in the remote gulf province of Papua New Guinea: a prospective study. BMC Infect Dis 2014; 14:93 [View Article][PubMed]
    [Google Scholar]
  15. Western Province TB Program Report Western Province TB Program Report; 2016
  16. Final Figures Papua New Guinea National Population and Housing Census 2011 [press release]; 2011
  17. Aia P, Kal M, Lavu E, John LN, Johnson K et al. The burden of drug-resistant tuberculosis in Papua New Guinea: results of a large population-based survey. PLoS One 2016; 11:e0149806 [View Article][PubMed]
    [Google Scholar]
  18. Supply P, Allix C, Lesjean S, Cardoso-Oelemann M, Rüsch-Gerdes S et al. Proposal for standardization of optimized mycobacterial interspersed repetitive unit-variable-number tandem repeat typing of Mycobacterium tuberculosis . J Clin Microbiol 2006; 44:4498–4510 [View Article][PubMed]
    [Google Scholar]
  19. Krüüner A, Yates MD, Drobniewski FA. Evaluation of MGIT 960-based antimicrobial testing and determination of critical concentrations of first- and second-line antimicrobial drugs with drug-resistant clinical strains of Mycobacterium tuberculosis . J Clin Microbiol 2006; 44:811–818 [View Article][PubMed]
    [Google Scholar]
  20. Ballif M, Harino P, Ley S, Coscolla M, Niemann S et al. Drug resistance-conferring mutations in Mycobacterium tuberculosis from Madang, Papua New Guinea. BMC Microbiol 2012; 12:191 [View Article][PubMed]
    [Google Scholar]
  21. Coll F, Mallard K, Preston MD, Bentley S, Parkhill J et al. SpolPred: rapid and accurate prediction of Mycobacterium tuberculosis spoligotypes from short genomic sequences. Bioinformatics 2012; 28:2991–2993 [View Article][PubMed]
    [Google Scholar]
  22. Demay C, Liens B, Burguière T, Hill V, Couvin D et al. SITVITWEB-a publicly available international multimarker database for studying Mycobacterium tuberculosis genetic diversity and molecular epidemiology. Infect Genet Evol 2012; 12:755–766 [View Article][PubMed]
    [Google Scholar]
  23. FastQC: a quality control tool for high throughput sequence data 2010; Available online at:. www.bioinformatics.babraham.ac.uk/projects/fastqc [Internet]
  24. Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 2014; 30:2114–2120 [View Article][PubMed]
    [Google Scholar]
  25. Li H. Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM. arXiv 20131303.3997v1
    [Google Scholar]
  26. McKenna A, Hanna M, Banks E, Sivachenko A, Cibulskis K et al. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res 2010; 20:1297–1303 [View Article][PubMed]
    [Google Scholar]
  27. Cingolani P, Platts A, Wang le L, Coon M, Nguyen T et al. A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff: SNPs in the genome of Drosophila melanogaster strain w1118; iso-2; iso-3. Fly 2012; 6:80–92 [View Article][PubMed]
    [Google Scholar]
  28. Guerra-Assunção JA, Crampin AC, Houben RM, Mzembe T, Mallard K et al. Large-scale whole genome sequencing of M. tuberculosis provides insights into transmission in a high prevalence area. Elife 2015; 4: [View Article][PubMed]
    [Google Scholar]
  29. Stamatakis A, Hoover P, Rougemont J. A rapid bootstrap algorithm for the RAxML Web servers. Syst Biol 2008; 57:758–771 [View Article][PubMed]
    [Google Scholar]
  30. Drummond AJ, Suchard MA, Xie D, Rambaut A. Bayesian phylogenetics with BEAUti and the BEAST 1.7. Mol Biol Evol 2012; 29:1969–1973 [View Article][PubMed]
    [Google Scholar]
  31. Merker M, Blin C, Mona S, Duforet-Frebourg N, Lecher S et al. Evolutionary history and global spread of the Mycobacterium tuberculosis Beijing lineage. Nat Genet 2015; 47:242–249 [View Article][PubMed]
    [Google Scholar]
  32. Luo T, Comas I, Luo D, Lu B, Wu J et al. Southern East Asian origin and coexpansion of Mycobacterium tuberculosis Beijing family with Han Chinese. Proc Natl Acad Sci USA 2015; 112:8136–8141 [View Article][PubMed]
    [Google Scholar]
  33. Ford CB, Shah RR, Maeda MK, Gagneux S, Murray MB et al. Mycobacterium tuberculosis mutation rate estimates from different lineages predict substantial differences in the emergence of drug-resistant tuberculosis. Nat Genet 2013; 45:784–790 [View Article][PubMed]
    [Google Scholar]
  34. Walker TM, Ip CL, Harrell RH, Evans JT, Kapatai G et al. Whole-genome sequencing to delineate Mycobacterium tuberculosis outbreaks: a retrospective observational study. Lancet Infect Dis 2013; 13:137–146 [View Article][PubMed]
    [Google Scholar]
  35. Bryant JM, Schürch AC, van Deutekom H, Harris SR, de Beer JL et al. Inferring patient to patient transmission of Mycobacterium tuberculosis from whole genome sequencing data. BMC Infect Dis 2013; 13:110 [View Article][PubMed]
    [Google Scholar]
  36. Baele G, Li WL, Drummond AJ, Suchard MA, Lemey P. Accurate model selection of relaxed molecular clocks in bayesian phylogenetics. Mol Biol Evol 2013; 30:239–243 [View Article][PubMed]
    [Google Scholar]
  37. Ford CB, Lin PL, Chase MR, Shah RR, Iartchouk O et al. Use of whole genome sequencing to estimate the mutation rate of Mycobacterium tuberculosis during latent infection. Nat Genet 2011; 43:482–486 [View Article][PubMed]
    [Google Scholar]
  38. Merker M, Kohl TA, Roetzer A, Truebe L, Richter E et al. Whole genome sequencing reveals complex evolution patterns of multidrug-resistant Mycobacterium tuberculosis Beijing strains in patients. PLoS One 2013; 8:e82551 [View Article][PubMed]
    [Google Scholar]
  39. Manson AL, Cohen KA, Abeel T, Desjardins CA, Armstrong DT et al. Genomic analysis of globally diverse Mycobacterium tuberculosis strains provides insights into the emergence and spread of multidrug resistance. Nat Genet 2017; 49:395–402 [View Article][PubMed]
    [Google Scholar]
  40. Coll F, McNerney R, Guerra-Assunção JA, Glynn JR, Perdigão J et al. A robust SNP barcode for typing Mycobacterium tuberculosis complex strains. Nat Commun 2014; 5:4812 [View Article][PubMed]
    [Google Scholar]
  41. Ley SD, Harino P, Vanuga K, Kamus R, Carter R et al. Diversity of Mycobacterium tuberculosis and drug resistance in different provinces of Papua New Guinea. BMC Microbiol 2014; 14:307 [View Article][PubMed]
    [Google Scholar]
  42. Ley SD, Riley I, Beck HP. Tuberculosis in Papua New Guinea: from yesterday until today. Microbes Infect 2014; 16:607–614 [View Article][PubMed]
    [Google Scholar]
  43. Domínguez J, Boettger EC, Cirillo D, Cobelens F, Eisenach KD et al. Clinical implications of molecular drug resistance testing for Mycobacterium tuberculosis: a TBNET/RESIST-TB consensus statement. Int J Tuberc Lung Dis 2016; 20:24–42 [View Article][PubMed]
    [Google Scholar]
  44. Marais BJ, Victor TC, Hesseling AC, Barnard M, Jordaan A et al. Beijing and Haarlem genotypes are overrepresented among children with drug-resistant tuberculosis in the Western Cape Province of South Africa. J Clin Microbiol 2006; 44:3539–3543 [View Article][PubMed]
    [Google Scholar]
  45. Machado D, Perdigão J, Ramos J, Couto I, Portugal I et al. High-level resistance to isoniazid and ethionamide in multidrug-resistant Mycobacterium tuberculosis of the Lisboa family is associated with inhA double mutations. J Antimicrob Chemother 2013; 68:1728–1732 [View Article][PubMed]
    [Google Scholar]
  46. Ogbunugafor CB, Wylie CS, Diakite I, Weinreich DM, Hartl DL. Adaptive landscape by environment interactions dictate evolutionary dynamics in models of drug resistance. PLoS Comput Biol 2016; 12:e1004710 [View Article][PubMed]
    [Google Scholar]
  47. Lee AS, Teo AS, Wong SY. Novel mutations in ndh in isoniazid-resistant Mycobacterium tuberculosis isolates. Antimicrob Agents Chemother 2001; 45:2157–2159 [View Article][PubMed]
    [Google Scholar]
  48. Ramaswamy SV, Dou SJ, Rendon A, Yang Z, Cave MD et al. Genotypic analysis of multidrug-resistant Mycobacterium tuberculosis isolates from Monterrey, Mexico. J Med Microbiol 2004; 53:107–113 [View Article][PubMed]
    [Google Scholar]
  49. Schmalstieg AM, Srivastava S, Belkaya S, Deshpande D, Meek C et al. The antibiotic resistance arrow of time: efflux pump induction is a general first step in the evolution of mycobacterial drug resistance. Antimicrob Agents Chemother 2012; 56:4806–4815 [View Article][PubMed]
    [Google Scholar]
  50. Ohol YM, Goetz DH, Chan K, Shiloh MU, Craik CS et al. Mycobacterium tuberculosis MycP1 protease plays a dual role in regulation of ESX-1 secretion and virulence. Cell Host Microbe 2010; 7:210–220 [View Article][PubMed]
    [Google Scholar]
  51. Simeone R, Bobard A, Lippmann J, Bitter W, Majlessi L et al. Phagosomal rupture by Mycobacterium tuberculosis results in toxicity and host cell death. PLoS Pathog 2012; 8:e1002507 [View Article][PubMed]
    [Google Scholar]
  52. Solomonson M, Huesgen PF, Wasney GA, Watanabe N, Gruninger RJ et al. Structure of the mycosin-1 protease from the mycobacterial ESX-1 protein type VII secretion system. J Biol Chem 2013; 288:17782–17790 [View Article][PubMed]
    [Google Scholar]
  53. Hoek KG, Schaaf HS, Gey van Pittius NC, van Helden PD, Warren RM. Resistance to pyrazinamide and ethambutol compromises MDR/XDR-TB treatment. S Afr Med J 2009; 99:785–787[PubMed]
    [Google Scholar]
  54. Zhao LL, Sun Q, Liu HC, Wu XC, Xiao TY et al. Analysis of embCAB mutations associated with ethambutol resistance in multidrug-resistant Mycobacterium tuberculosis isolates from China. Antimicrob Agents Chemother 2015; 59:2045–2050 [View Article][PubMed]
    [Google Scholar]
  55. Safi H, Lingaraju S, Amin A, Kim S, Jones M et al. Evolution of high-level ethambutol-resistant tuberculosis through interacting mutations in decaprenylphosphoryl-β-D-arabinose biosynthetic and utilization pathway genes. Nat Genet 2013; 45:1190–1197 [View Article][PubMed]
    [Google Scholar]
  56. Borisov SE, Dheda K, Enwerem M, Romero Leyet R, D'Ambrosio L et al. Effectiveness and safety of bedaquiline-containing regimens in the treatment of MDR- and XDR-TB: a multicentre study. Eur Respir J 2017; 49:1700387 [View Article][PubMed]
    [Google Scholar]
  57. Georghiou SB, Magana M, Garfein RS, Catanzaro DG, Catanzaro A et al. Evaluation of genetic mutations associated with Mycobacterium tuberculosis resistance to amikacin, kanamycin and capreomycin: a systematic review. PLoS One 2012; 7:e33275 [View Article][PubMed]
    [Google Scholar]
  58. World Health Organization The use of molecular line probe assays for the detection of resistance to second-line anti-tuberculosis drugs. Geneva: Switzerland 2016
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