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Volume 9, Issue 5

Lack of methoxy-mycolates characterizes the geographically restricted lineage 7 of complex Open Access

Abstract

Lineage 7 (L7) emerged in the phylogeny of the complex (MTBC) subsequent to the branching of ‘ancient’ lineage 1 and prior to the Eurasian dispersal of ‘modern’ lineages 2, 3 and 4. In contrast to the major MTBC lineages, the current epidemiology suggests that prevalence of L7 is highly confined to the Ethiopian population, or when identified outside of Ethiopia, it has mainly been in patients of Ethiopian origin. To search for microbiological factors that may contribute to its restricted distribution, we compared the genome of L7 to the genomes of globally dispersed MTBC lineages. The frequency of predicted functional mutations in L7 was similar to that documented in other lineages. These include mutations characteristic of modern lineages – such as constitutive expression of nitrate reductase – as well as mutations in the VirS locus that are commonly found in ancient lineages. We also identified and characterized multiple lineage-specific mutations in L7 in biosynthesis pathways of cell wall lipids, including confirmed deficiency of methoxy-mycolic acids due to a stop-gain mutation in the gene that encodes a methoxy-mycolic acid synthase. We show that the abolished biosynthesis of methoxy-mycolates of L7 alters the cell structure and colony morphology on selected growth media and impacts biofilm formation. The loss of these mycolic acid moieties may change the host–pathogen dynamic for L7 isolates, explaining the limited geographical distribution of L7 and contributing to further understanding the spread of MTBC lineages across the globe.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): cell wall , cord factor , genomics , lineage 7 , methoxy-mycolates and Mycobacterium tuberculosis
Funding
This study was supported by the:
  • ISSF Wellcome Trust (Award 204833/Z/16/Z)
    • Principle Award Recipient: SimonJ Waddell
  • MRC Confidence in Concept Fund (Award 105603/Z/14/Z)
    • Principle Award Recipient: GeraldLarrouy-Maumus
© 2023 Crown Copyright
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.

Erratum

An erratum has been published for this content:
Corrigendum: Lack of methoxy-mycolates characterizes the geographically restricted lineage 7 of complex
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References

  1. WHO Global Tuberculosis Report Geneva: World Health Organization; 2021
     [Google Scholar]
  2. Smith NH, Kremer K, Inwald J, Dale J, Driscoll JR et al. Ecotypes of the Mycobacterium tuberculosis complex. J Theor Biol 2006; 239:220–225 [View Article] [PubMed]
     [Google Scholar]
  3. WHOOIEFAOThe Union Roadmap for Zoonotic Tuberculosis, Report No. 978 92 4 151304 3 Geneva: World Health Organization; 2017
     [Google Scholar]
  4. Duffy SC, Srinivasan S, Schilling MA, Stuber T, Danchuk SN et al. Reconsidering Mycobacterium bovis as a proxy for zoonotic tuberculosis: a molecular epidemiological surveillance study. Lancet Microbe 2020; 1:e66–e73 [View Article] [PubMed]
     [Google Scholar]
  5. Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 1998; 393:537–544 [View Article] [PubMed]
     [Google Scholar]
  6. Gutacker MM, Smoot JC, Migliaccio CAL, Ricklefs SM, Hua S et al. Genome-wide analysis of synonymous single nucleotide polymorphisms in Mycobacterium tuberculosis complex organisms: resolution of genetic relationships among closely related microbial strains. Genetics 2002; 162:1533–1543 [View Article] [PubMed]
     [Google Scholar]
  7. Brosch R, Gordon SV, Marmiesse M, Brodin P, Buchrieser C et al. A new evolutionary scenario for the Mycobacterium tuberculosis complex. Proc Natl Acad Sci U S A 2002; 99:3684–3689 [View Article] [PubMed]
     [Google Scholar]
  8. de Jong BC, Antonio M, Gagneux S. Mycobacterium africanum – review of an important cause of human tuberculosis in West Africa. PLoS Negl Trop Dis 2010; 4:e744 [View Article] [PubMed]
     [Google Scholar]
  9. Gagneux S, DeRiemer K, Van T, Kato-Maeda M, de Jong BC et al. Variable host-pathogen compatibility in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 2006; 103:2869–2873 [View Article] [PubMed]
     [Google Scholar]
  10. Comas I, Gagneux S. A role for systems epidemiology in tuberculosis research. Trends Microbiol 2011; 19:492–500 [View Article] [PubMed]
     [Google Scholar]
  11. Hershberg R, Lipatov M, Small PM, Sheffer H, Niemann S et al. High functional diversity in Mycobacterium tuberculosis driven by genetic drift and human demography. PLoS Biol 2008; 6:e311 [View Article] [PubMed]
     [Google Scholar]
  12. Firdessa R, Berg S, Hailu E, Schelling E, Gumi B et al. Mycobacterial lineages causing pulmonary and extrapulmonary tuberculosis, Ethiopia. Emerg Infect Dis 2013; 19:460–463 [View Article] [PubMed]
     [Google Scholar]
  13. Blouin Y, Hauck Y, Soler C, Fabre M, Vong R et al. Significance of the identification in the Horn of Africa of an exceptionally deep branching Mycobacterium tuberculosis clade. PLoS One 2012; 7:e52841 [View Article] [PubMed]
     [Google Scholar]
  14. Coscolla M, Gagneux S, Menardo F, Loiseau C, Ruiz-Rodriguez P et al. Phylogenomics of Mycobacterium africanum reveals a new lineage and a complex evolutionary history. Microb Genom 2021; 7:000477 [View Article] [PubMed]
     [Google Scholar]
  15. Ngabonziza JCS, Loiseau C, Marceau M, Jouet A, Menardo F et al. A sister lineage of the Mycobacterium tuberculosis complex discovered in the African Great Lakes region. Nat Commun 2020; 11:2917 [View Article] [PubMed]
     [Google Scholar]
  16. Mekonnen D, Derbie A, Chanie A, Shumet A, Biadglegne F et al. Molecular epidemiology of M. tuberculosis in Ethiopia: a systematic review and meta-analysis. Tuberculosis 2019; 118:101858 [View Article] [PubMed]
     [Google Scholar]
  17. Baya B, Diarra B, Diabate S, Kone B, Goita D et al. Association of Mycobacterium africanum infection with slower disease progression compared with Mycobacterium tuberculosis in Malian patients with tuberculosis. Am J Trop Med Hyg 2020; 102:36–41 [View Article] [PubMed]
     [Google Scholar]
  18. Coscolla M, Gagneux S. Consequences of genomic diversity in Mycobacterium tuberculosis. Semin Immunol 2014; 26:431–444 [View Article] [PubMed]
     [Google Scholar]
  19. Cadena AM, Fortune SM, Flynn JL. Heterogeneity in tuberculosis. Nat Rev Immunol 2017; 17:691–702 [View Article] [PubMed]
     [Google Scholar]
  20. Gygli SM, Borrell S, Trauner A, Gagneux S. Antimicrobial resistance in Mycobacterium tuberculosis: mechanistic and evolutionary perspectives. FEMS Microbiol Rev 2017; 41:354–373 [View Article] [PubMed]
     [Google Scholar]
  21. Pareek M, Evans J, Innes J, Smith G, Hingley-Wilson S et al. Ethnicity and mycobacterial lineage as determinants of tuberculosis disease phenotype. Thorax 2013; 68:221–229 [View Article] [PubMed]
     [Google Scholar]
  22. Asante-Poku A, Yeboah-Manu D, Otchere ID, Aboagye SY, Stucki D et al. Mycobacterium africanum is associated with patient ethnicity in Ghana. PLoS Negl Trop Dis 2015; 9:e3370 [View Article] [PubMed]
     [Google Scholar]
  23. Yimer SA, Norheim G, Namouchi A, Zegeye ED, Kinander W et al. Mycobacterium tuberculosis lineage 7 strains are associated with prolonged patient delay in seeking treatment for pulmonary tuberculosis in Amhara Region, Ethiopia. J Clin Microbiol 2015; 53:1301–1309 [View Article] [PubMed]
     [Google Scholar]
  24. Yimer SA, Namouchi A, Zegeye ED, Holm-Hansen C, Norheim G et al. Deciphering the recent phylogenetic expansion of the originally deeply rooted Mycobacterium tuberculosis lineage 7. BMC Evol Biol 2016; 16:146 [View Article] [PubMed]
     [Google Scholar]
  25. Nebenzahl-Guimaraes H, Yimer SA, Holm-Hansen C, de Beer J, Brosch R et al. Genomic characterization of Mycobacterium tuberculosis lineage 7 and a proposed name: “Aethiops vetus.”. Microb Genom 2016; 2:e000063 [View Article] [PubMed]
     [Google Scholar]
  26. Yimer SA, Birhanu AG, Kalayou S, Riaz T, Zegeye ED et al. Comparative proteomic analysis of Mycobacterium tuberculosis lineage 7 and lineage 4 strains reveals differentially abundant proteins linked to slow growth and virulence. Front Microbiol 2017; 8:795 [View Article] [PubMed]
     [Google Scholar]
  27. Birhanu AG, Yimer SA, Holm-Hansen C, Norheim G, Aseffa A et al. Nε- and O-acetylation in Mycobacterium tuberculosis lineage 7 and lineage 4 strains: proteins involved in bioenergetics, virulence, and antimicrobial resistance are acetylated. J Proteome Res 2017; 16:4045–4059 [View Article] [PubMed]
     [Google Scholar]
  28. Yuan Y, Lee RE, Besra GS, Belisle JT, Barry CE. Identification of a gene involved in the biosynthesis of cyclopropanated mycolic acids in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 1995; 92:6630–6634 [View Article] [PubMed]
     [Google Scholar]
  29. Yuan Y, Zhu Y, Crane DD, Barry CE 3rd. The effect of oxygenated mycolic acid composition on cell wall function and macrophage growth in Mycobacterium tuberculosis. Mol Microbiol 1998; 29:1449–1458 [View Article] [PubMed]
     [Google Scholar]
  30. BLOCH H. Studies on the virulence of tubercle bacilli; isolation and biological properties of a constituent of virulent organisms. J Exp Med 1950; 91:197–218 [View Article] [PubMed]
     [Google Scholar]
  31. Asselineau J, Buc H, Jolles P, Lederer E. [Chemical structure of a peptide-glycolipid fraction (wax D) isolated from Mycobacterium tuberculosis var. hominis]. Bull Soc Chim Biol 1958; 40:1953–1964
     [Google Scholar]
  32. Tanaka A, Tanaka K, Tsubone T, Kuroda Y, Sugiyama K. Fractionation and characterization of wax D, a peptidoglycolipid of Mycobacterium tuberculosis. II Adjuvanticity of the subfractions of wax D of H37Ra and wax D of other strains M. tuberculosis. Int Arch Allergy Appl Immunol 1965; 28:340–352 [View Article] [PubMed]
     [Google Scholar]
  33. Kanetsuna F, Blas GS. Chemical analysis of a mycolic acid-arabinogalactan-mucopeptide complex of mycobacterial cell wall. Biochim Biophys Acta 1970; 208:434–443 [View Article] [PubMed]
     [Google Scholar]
  34. Brennan PJ, Nikaido H. The envelope of mycobacteria. Annu Rev Biochem 1995; 64:29–63 [View Article] [PubMed]
     [Google Scholar]
  35. Verschoor JA, Baird MS, Grooten J. Towards understanding the functional diversity of cell wall mycolic acids of Mycobacterium tuberculosis. Prog Lipid Res 2012; 51:325–339 [View Article] [PubMed]
     [Google Scholar]
  36. PaweŁczyk J, Kremer L. The molecular genetics of mycolic acid biosynthesis. Microbiol Spectr 2014; 2:MGM2-0003-2013 [View Article] [PubMed]
     [Google Scholar]
  37. Slama N, Jamet S, Frigui W, Pawlik A, Bottai D et al. The changes in mycolic acid structures caused by hadC mutation have a dramatic effect on the virulence of Mycobacterium tuberculosis. Mol Microbiol 2016; 99:794–807 [View Article] [PubMed]
     [Google Scholar]
  38. Vermeulen I, Baird M, Al-Dulayymi J, Smet M, Verschoor J et al. Mycolates of Mycobacterium tuberculosis modulate the flow of cholesterol for bacillary proliferation in murine macrophages. J Lipid Res 2017; 58:709–718 [View Article] [PubMed]
     [Google Scholar]
  39. Palomino JC, Martin A, Camacho M, Guerra H, Swings J et al. Resazurin microtiter assay plate: simple and inexpensive method for detection of drug resistance in Mycobacterium tuberculosis. Antimicrob Agents Chemother 2002; 46:2720–2722 [View Article] [PubMed]
     [Google Scholar]
  40. Meehan CJ, Goig GA, Kohl TA, Verboven L, Dippenaar A et al. Whole genome sequencing of Mycobacterium tuberculosis: current standards and open issues. Nat Rev Microbiol 2019; 17:533–545 [View Article] [PubMed]
     [Google Scholar]
  41. Chen S, Zhou Y, Chen Y, Gu J. fastp: an ultra-fast all-in-one FASTQ preprocessor. Bioinformatics 2018; 34:i884–i890 [View Article] [PubMed]
     [Google Scholar]
  42. Wood DE, Salzberg SL. Kraken: ultrafast metagenomic sequence classification using exact alignments. Genome Biol 2014; 15:R46 [View Article] [PubMed]
     [Google Scholar]
  43. Li H, Durbin R. Fast and accurate short read alignment with Burrows-Wheeler transform. Bioinformatics 2009; 25:1754–1760 [View Article] [PubMed]
     [Google Scholar]
  44. Comas I, Chakravartti J, Small PM, Galagan J, Niemann S et al. Human T cell epitopes of Mycobacterium tuberculosis are evolutionarily hyperconserved. Nat Genet 2010; 42:498–503 [View Article] [PubMed]
     [Google Scholar]
  45. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J et al. The Sequence Alignment/Map format and SAMtools. Bioinformatics 2009; 25:2078–2079 [View Article] [PubMed]
     [Google Scholar]
  46. Picard Toolkit: Broad Institute, GitHub Repository; 2019 http://broadinstitute.github.io/picard
  47. Koboldt DC, Zhang Q, Larson DE, Shen D, McLellan MD et al. VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing. Genome Res 2012; 22:568–576 [View Article] [PubMed]
     [Google Scholar]
  48. Chiner-Oms A, Lopez MG, Moreno-Molina M, Furio V, Comas I. Gene evolutionary trajectories in Mycobacterium tuberculosis reveal temporal signs of selection. PNAS 2022; 117:e211360011 [View Article]
     [Google Scholar]
  49. Cingolani P, Platts A, Wang LL, Coon M, Nguyen T et al. A program for annotating and predicting the effects of single nucleotide polymorphisms, SnpEff. Fly 2012; 6:80–92 [View Article]
     [Google Scholar]
  50. Minh BQ, Schmidt HA, Chernomor O, Schrempf D, Woodhams MD et al. IQ-TREE 2: new models and efficient methods for phylogenetic inference in the genomic era. Mol Biol Evol 2020; 37:1530–1534 [View Article] [PubMed]
     [Google Scholar]
  51. Maddison WP, Maddison DR. Mesquite: a modular system for evolutionary analysis, version 3.70 2021 http://www.mesquiteproject.org
  52. Ng PC, Henikoff S. SIFT: predicting amino acid changes that affect protein function. Nucleic Acids Res 2003; 31:3812–3814 [View Article] [PubMed]
     [Google Scholar]
  53. Sim NL, Kumar P, Hu J, Henikoff S, Schneider G et al. SIFT web server: predicting effects of amino acid substitutions on proteins. Nucleic Acids Res 2012; 40:W452–W457 [View Article] [PubMed]
     [Google Scholar]
  54. Lu S, Wang J, Chitsaz F, Derbyshire MK, Geer RC et al. CDD/SPARCLE: the conserved domain database in 2020. Nucleic Acids Res 2020; 48:D265–D268 [View Article] [PubMed]
     [Google Scholar]
  55. Duvaud S, Gabella C, Lisacek F, Stockinger H, Ioannidis V et al. Expasy, the Swiss Bioinformatics Resource Portal, as designed by its users. Nucleic Acids Res 2021; 49:W216–W227 [View Article] [PubMed]
     [Google Scholar]
  56. Wheeler PR, Brosch R, Coldham NG, Inwald JK, Hewinson RG et al. Functional analysis of a clonal deletion in an epidemic strain of Mycobacterium bovis reveals a role in lipid metabolism. Microbiology 2008; 154:3731–3742 [View Article] [PubMed]
     [Google Scholar]
  57. Dobson G, Minnikin DE, Minnikin SM, Parlett JH, Ridell M et al. Systematic analysis of complex mycobacterial lipids. In Goodfellow M, Minnikin DE. eds Chemical Methods in Bacterial Systematics London: Academic Press; 1985 pp 237–265
     [Google Scholar]
  58. Wheeler PR. Analysis of lipid biosynthesis and location. In Parish T, Brown A. eds Mycobacteria Protocols, 2nd edn. Totowa, NJ: Humana Press; 2008 pp 61–82 [View Article]
     [Google Scholar]
  59. Barry CE 3rd, Lee RE, Mdluli K, Sampson AE, Schroeder BG et al. Mycolic acids: structure, biosynthesis and physiological functions. Prog Lipid Res 1998; 37:143–179 [View Article] [PubMed]
     [Google Scholar]
  60. Kulka K, Hatfull G, Ojha AK. Growth of Mycobacterium tuberculosis biofilms. J Vis Exp 2012; 60:3820
     [Google Scholar]
  61. Kamerbeek J, Schouls L, Kolk A, van Agterveld M, van Soolingen D et al. Simultaneous detection and strain differentiation of Mycobacterium tuberculosis for diagnosis and epidemiology. J Clin Microbiol 1997; 35:907–914 [View Article] [PubMed]
     [Google Scholar]
  62. Comas I, Hailu E, Kiros T, Bekele S, Mekonnen W et al. Population genomics of Mycobacterium tuberculosis in Ethiopia contradicts the virgin soil hypothesis for human tuberculosis in Sub-Saharan Africa. Curr Biol 2015; 25:3260–3266 [View Article] [PubMed]
     [Google Scholar]
  63. Huet G, Constant P, Malaga W, Lanéelle M-A, Kremer K et al. A lipid profile typifies the Beijing strains of Mycobacterium tuberculosis: identification of a mutation responsible for a modification of the structures of phthiocerol dimycocerosates and phenolic glycolipids. J Biol Chem 2009; 284:27101–27113 [View Article] [PubMed]
     [Google Scholar]
  64. Constant P, Perez E, Malaga W, Lanéelle M-A, Saurel O et al. Role of the pks15/1 gene in the biosynthesis of phenolglycolipids in the Mycobacterium tuberculosis complex. Evidence that all strains synthesize glycosylated p-hydroxybenzoic methyl esters and that strains devoid of phenolglycolipids harbor a frameshift mutation in the pks15/1 gene. J Biol Chem 2002; 277:38148–38158 [View Article] [PubMed]
     [Google Scholar]
  65. Singh A, Jain S, Gupta S, Das T, Tyagi AK. mymA operon of Mycobacterium tuberculosis: its regulation and importance in the cell envelope. FEMS Microbiol Lett 2003; 227:53–63 [View Article] [PubMed]
     [Google Scholar]
  66. Chiner-Oms Á, López MG, Moreno-Molina M, Furió V, Comas I. Gene evolutionary trajectories in Mycobacterium tuberculosis reveal temporal signs of selection. Proc Natl Acad Sci U S A 2022; 119:e2113600119 [View Article] [PubMed]
     [Google Scholar]
  67. Ingrosso D, Fowler AV, Bleibaum J, Clarke S. Sequence of the D-aspartyl/L-isoaspartyl protein methyltransferase from human erythrocytes. Common sequence motifs for protein, DNA, RNA, and small molecule S-adenosylmethionine-dependent methyltransferases. J Biol Chem 1989; 264:20131–20139 [PubMed]
     [Google Scholar]
  68. Peña CE, Stoner JE, Hatfull GF. Positions of strand exchange in mycobacteriophage L5 integration and characterization of the attB site. J Bacteriol 1996; 178:5533–5536 [View Article] [PubMed]
     [Google Scholar]
  69. Schaefer WB. Growth requirements of dysgonic and eugonic strains of Mycobacterium tuberculosis var. bovis. J Exp Med 1952; 96:207–219 [View Article] [PubMed]
     [Google Scholar]
  70. Rose G, Cortes T, Comas I, Coscolla M, Gagneux S et al. Mapping of genotype-phenotype diversity among clinical isolates of Mycobacterium tuberculosis by sequence-based transcriptional profiling. Genome Biol Evol 2013; 5:1849–1862 [View Article] [PubMed]
     [Google Scholar]
  71. Øyås O, Borrell S, Trauner A, Zimmermann M, Feldmann J et al. Model-based integration of genomics and metabolomics reveals SNP functionality in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 2020; 117:8494–8502 [View Article] [PubMed]
     [Google Scholar]
  72. Reed MB, Domenech P, Manca C, Su H, Barczak AK et al. A glycolipid of hypervirulent tuberculosis strains that inhibits the innate immune response. Nature 2004; 431:84–87 [View Article] [PubMed]
     [Google Scholar]
  73. Singh A, Gupta R, Vishwakarma RA, Narayanan PR, Paramasivan CN et al. Requirement of the mymA operon for appropriate cell wall ultrastructure and persistence of Mycobacterium tuberculosis in the spleens of guinea pigs. J Bacteriol 2005; 187:4173–4186 [View Article] [PubMed]
     [Google Scholar]
  74. Zhang C-X, Luo T, Ma P-J, Wang C-H, Suo J et al. Mycobacterium tuberculosis Rv3084 encodes functional esterase and suppresses the pro-inflammatory cytokines in vivo.. Sichuan Da Xue Xue Bao Yi Xue Ban 2019; 50:291–297 [PubMed]
     [Google Scholar]
  75. Villeneuve M, Kawai M, Horiuchi K, Watanabe M, Aoyagi Y et al. Conformational folding of mycobacterial methoxy- and ketomycolic acids facilitated by α-methyl trans-cyclopropane groups rather than cis-cyclopropane units. Microbiology 2013; 159:2405–2415 [View Article] [PubMed]
     [Google Scholar]
  76. Tahlan K, Wilson R, Kastrinsky DB, Arora K, Nair V et al. SQ109 targets MmpL3, a membrane transporter of trehalose monomycolate involved in mycolic acid donation to the cell wall core of Mycobacterium tuberculosis. Antimicrob Agents Chemother 2012; 56:1797–1809 [View Article] [PubMed]
     [Google Scholar]
  77. Chakraborty P, Bajeli S, Kaushal D, Radotra BD, Kumar A. Biofilm formation in the lung contributes to virulence and drug tolerance of Mycobacterium tuberculosis. Nat Commun 2021; 12:1606 [View Article] [PubMed]
     [Google Scholar]
  78. Ojha AK, Baughn AD, Sambandan D, Hsu T, Trivelli X et al. Growth of Mycobacterium tuberculosis biofilms containing free mycolic acids and harbouring drug-tolerant bacteria. Mol Microbiol 2008; 69:164–174 [View Article] [PubMed]
     [Google Scholar]
  79. Glickman MS, Cox JS, Jacobs WR. A novel mycolic acid cyclopropane synthetase is required for cording, persistence, and virulence of Mycobacterium tuberculosis. Mol Cell 2000; 5:717–727 [View Article] [PubMed]
     [Google Scholar]
  80. Barkan D, Hedhli D, Yan HG, Huygen K, Glickman MS. Mycobacterium tuberculosis lacking all mycolic acid cyclopropanation is viable but highly attenuated and hyperinflammatory in mice. Infect Immun 2012; 80:1958–1968 [View Article] [PubMed]
     [Google Scholar]
  81. Dao DN, Sweeney K, Hsu T, Gurcha SS, Nascimento IP et al. Mycolic acid modification by the mmaA4 gene of M. tuberculosis modulates IL-12 production. PLoS Pathog 2008; 4:e1000081 [View Article] [PubMed]
     [Google Scholar]
  82. Behr MA, Schroeder BG, Brinkman JN, Slayden RA, Barry CE. A point mutation in the mma3 gene is responsible for impaired methoxymycolic acid production in Mycobacterium bovis BCG strains obtained after 1927. J Bacteriol 2000; 182:3394–3399 [View Article] [PubMed]
     [Google Scholar]
  83. Hayashi D, Takii T, Fujiwara N, Fujita Y, Yano I et al. Comparable studies of immunostimulating activities in vitro among Mycobacterium bovis bacillus Calmette-Guérin (BCG) substrains. FEMS Immunol Med Microbiol 2009; 56:116–128 [View Article] [PubMed]
     [Google Scholar]
  84. Vander Beken S, Al Dulayymi JR, Naessens T, Koza G, Maza-Iglesias M et al. Molecular structure of the Mycobacterium tuberculosis virulence factor, mycolic acid, determines the elicited inflammatory pattern. Eur J Immunol 2011; 41:450–460 [View Article] [PubMed]
     [Google Scholar]
  85. Rao V, Gao F, Chen B, Jacobs WR, Glickman MS. Trans-cyclopropanation of mycolic acids on trehalose dimycolate suppresses Mycobacterium tuberculosis -induced inflammation and virulence. J Clin Invest 2006; 116:1660–1667 [View Article] [PubMed]
     [Google Scholar]
  86. Sambandan D, Dao DN, Weinrick BC, Vilchèze C, Gurcha SS et al. Keto-mycolic acid-dependent pellicle formation confers tolerance to drug-sensitive Mycobacterium tuberculosis. mBio 2013; 4:e00222-13 [View Article] [PubMed]
     [Google Scholar]
  87. Dubnau E, Chan J, Raynaud C, Mohan VP, Lanéelle MA et al. Oxygenated mycolic acids are necessary for virulence of Mycobacterium tuberculosis in mice. Mol Microbiol 2000; 36:630–637 [View Article] [PubMed]
     [Google Scholar]
  88. Gallagher J, Horwill DM. A selective oleic acid albumin agar medium for the cultivation of Mycobacterium bovis. J Hyg 1977; 79:155–160 [View Article] [PubMed]
     [Google Scholar]
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Lack of methoxy-mycolates characterizes the geographically restricted lineage 7 of Mycobacterium tuberculosis complex
M Gen 9, 001011 (2023); https://doi.org/10.1099/mgen.0.001011
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