Mycobacterium spp.

  • Douglas I. Johnson


  • Genomics:
    • Mycobacterium tuberculosis strain H37Rv chromosome: 4,411,529 bp; 4,006 predicted ORFs (Cole et al. 1998; Camus et al. 2002)

    • Mycobacterium leprae chromosome: 3,268,203 bp; 1,604 predicted ORFs (Cole et al. 2001)

    • Mycobacterium ulcerans chromosome – 5,631,606-bp; 4,160 predicted ORFs:
      • Plasmid pMUM001: 174,155 bp; 81 predicted ORFs; contains the gene products needed to synthesize mycolactone (see below) (Stinear et al. 2007)

  • Cell morphology:
    • Slender rod-shaped cells (Fig. 7.1):
      • Held together in parallel (serpentine) cords (Fig. 7.2) by cord factor (trehalose 6,6′-dimycolate; TDM); essential for virulence (see below)

    • Non-endospore former

    • No flagellar motility

  • Gram stain:
    • Gram positive; acid-fast staining due to hydrophobic cell wall constituents (see below)

  • Growth:
    • Obligate aerobes

    • Very slow growers: generation times from 12 to 24 h

    • Over 120 species – most are nonpathogenic environmental microbes; three are major human pathogens:
      • Mycobacterium tuberculosis: facultative intracellular pathogen of macrophage (not free-living)

      • Mycobacterium leprae: obligate intracellular pathogen of Schwann cells and macrophage (not free-living)

      • Mycobacterium ulcerans: extracellular pathogen


  1. Abdallah AM, Pittius NCG, Champion PAD, Cox J, Luirink J, Vandenbroucke-Grauls CMJE, Appelmelk BJ, Bitter W (2007) Type VII secretion — mycobacteria show the way. Nat Rev Microbiol 5:883–891CrossRefPubMedGoogle Scholar
  2. Abrahams KA, Besra GS (2016) Mycobacterial cell wall biosynthesis: a multifaceted antibiotic target. Parasitology:1–18.
  3. Alteri CJ, Xicohtencatl-Cortes J, Hess S, Caballero-Olin G, Giron JA, Friedman RL (2007) Mycobacterium tuberculosis produces pili during human infection. Proc NatI Acad Sci USA 104:5145–5150CrossRefGoogle Scholar
  4. Barker LP (2006) Mycobacterium leprae interactions with the host cell: recent advances. Ind J Med Res 123:748–759Google Scholar
  5. Bornemann S (2016) Alpha-glucan biosynthesis and the GlgE pathway in Mycobacterium tuberculosis. Biochem Soc Trans 44:68–73CrossRefPubMedGoogle Scholar
  6. Briken V, Porcelli SA, Besra GS, Kremer L (2004) Mycobacterial lipoarabinomannan and related lipoglycans: from biogenesis to modulation of the immune response. Mol Microbiol 53:391–403CrossRefPubMedGoogle Scholar
  7. Britton WJ, Lockwood DNJ (2004) Leprosy. Lancet 363:1209–1219CrossRefPubMedGoogle Scholar
  8. Broset E, Martin C, Gonzalo-Asensio J (2015) Evolutionary landscape of the mycobacterium tuberculosis complex from the viewpoint of PhoPR: implications for virulence regulation and application to vaccine development. MBio 6:e01289–e01215CrossRefPubMedPubMedCentralGoogle Scholar
  9. Brown L, Wolf JM, Prados-Rosales R, Casadevall A (2015) Through the wall: extracellular vesicles in gram-positive bacteria, mycobacteria and fungi. Nat Rev Microbiol 13:620–630CrossRefPubMedPubMedCentralGoogle Scholar
  10. Cambier CJ, Falkow S, Ramakrishnan L (2014a) Host evasion and exploitation schemes of Mycobacterium tuberculosis. Cell 159:1497–1509CrossRefPubMedGoogle Scholar
  11. Cambier CJ, Takaki KK, Larson RP, Hernandez RE, Tobin DM, Urdahl KB, Cosma CL, Ramakrishnan L (2014b) Mycobacteria manipulate macrophage recruitment through coordinated use of membrane lipids. Nature 505:218–222CrossRefPubMedGoogle Scholar
  12. Camus J-C, Pryor MJ, Medigue C, Cole ST (2002) Re-annotation of the genome sequence of Mycobacterium tuberculosis H37Rv. Microbiology 148:2967–2973CrossRefPubMedGoogle Scholar
  13. Cao G, Howard ST, Zhang P, Wang X, Chen XL, Samten B, Pang X (2015) EspR, a regulator of the ESX-1 secretion system in Mycobacterium tuberculosis, is directly regulated by the two-component systems MprAB and PhoPR. Microbiology 161:477–489CrossRefPubMedGoogle Scholar
  14. Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D, Gordon SV, Eiglmeier K, Gas S, C.E. Barry. I, Tekaia F, Badcock K, Basham D, Brown D, Chillingworth T, Connor R, Davies R, Devlin K, Feltwell T, Gentles S, Hamlin N, Holroyd S, Hornsby T, Jagels K, Krogh A, McLean J, Moule S, Murphy L, Oliver K, Osborne J, Quail MA, Rajandream M-A, Rogers J, Rutter S, Seeger K, Skelton J, Squares R, Squares S, Sulston JE, Taylor K, Whitehead S, Barrell BG (1998) Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature 393:537–544CrossRefPubMedGoogle Scholar
  15. Cole ST, Eiglmeier K, Parkhill J, James KD, Thomson NR, Wheeler PR, Honore N, Garnier T, Churcher C, Harris D, Mungall K, Basham D, Brown D, Chillingworth T, Connor R, Davies RM, Devlin K, Duthoy S, Feltwell T, Fraser A, Hamlin N, Holroyd S, Hornsby T, Jagels K, Lacroix C, Maclean J, Moule S, Murphy L, Oliver K, Quail MA, Rajandream M-A, Rutherford KM, Rutter S, Seeger K, Simon S, Simmonds M, Skelton J, Squares R, Squares S, Stevens K, Taylor K, Whitehead S, Woodward JR, Barrell BG (2001) Massive gene decay in the leprosy bacillus. Nature 409:1007–1011CrossRefPubMedGoogle Scholar
  16. Darwin KH, Ehrt S, Gutierrez-Ramos J-C, Weich N, Nathan CF (2003) The proteasome of Mycobacterium tuberculosis is required for resistance to nitric oxide. Science 302:1963–1967CrossRefPubMedGoogle Scholar
  17. Derrick SC, Morris SL (2007) The ESAT6 protein of Mycobacterium tuberculosis induces apoptosis of macrophages by activating caspase expression. Cell Microbiol 9:1547–1555CrossRefPubMedGoogle Scholar
  18. Desjardin LE, Hayes LG, Sohaskey CD, Wayne LG, Eisenach KD (2001) Microaerophilic induction of the alpha-crystallin chaperone protein homologue (hspX) mRNA of Mycobacterium tuberculosis. J Bacteriol 183:5311–5316CrossRefPubMedPubMedCentralGoogle Scholar
  19. Drage MG, Pecora ND, Hise AG, Febbraio M, Silverstein RL, Golenbock DT, Boom WH, Harding CV (2009) TLR2 and its co-receptors determine responses of macrophages and dendritic cells to lipoproteins of Mycobacterium tuberculosis. Cell Immunol 258:29–37CrossRefPubMedPubMedCentralGoogle Scholar
  20. Edwards KM, Cynamon MH, Voladri RK, Hager CC, DeStefano MS, Tham KT, Lakey DL, Bochan MR, Kernodle DS (2001) Iron-cofactored superoxide dismutase inhibits host responses to Mycobacterium tuberculosis. Am J Resp Crit Care Med 164:2213–2219CrossRefPubMedGoogle Scholar
  21. Franco-Paredes C, Rodriguez-Morales AJ (2016) Unsolved matters in leprosy: a descriptive review and call for further research. Ann Clin Microbiol Antimicrob 15:33CrossRefPubMedPubMedCentralGoogle Scholar
  22. Gold B, Rodriguez GM, Marras SAE, Pentecost M, Smith I (2001) The Mycobacterium tuberculosis IdeR is a dual functional regulator that controls transcription of genes involved in iron acquisition, iron storage and survival in macrophages. Mol Microbiol 42:851–865CrossRefPubMedGoogle Scholar
  23. Govender VS, Ramsugit S, Pillay M (2014) Mycobacterium tuberculosis adhesins: potential biomarkers as anti-tuberculosis therapeutic and diagnostic targets. Microbiology 160:1821–1831CrossRefPubMedGoogle Scholar
  24. Guenin-Mace L, Simeone R, Demangel C (2009) Lipids of pathogenic mycobacteria: contributions to virulence and host immune suppression. Transbound Emerg Dis 56:255–268CrossRefPubMedGoogle Scholar
  25. Guenin-Mace L, Veyron-Churlet R, Thoulouze MI, Romet-Lemonne G, Hong H, Leadlay PF, Danckaert A, Ruf MT, Mostowy S, Zurzolo C, Bousso P, Chretien F, Carlier MF, Demangel C (2013) Mycolactone activation of Wiskott-Aldrich syndrome proteins underpins Buruli ulcer formation. J Clin Investig 123:1501–1512CrossRefPubMedPubMedCentralGoogle Scholar
  26. Hall BS, Hill K, McKenna M, Ogbechi J, High S, Willis AE, Simmonds RE (2014) The pathogenic mechanism of the Mycobacterium ulcerans virulence factor, mycolactone, depends on blockade of protein translocation into the ER. PLoS Pathog 10:e1004061CrossRefPubMedPubMedCentralGoogle Scholar
  27. Hameed S, Pal R, Fatima Z (2015) Iron acquisition mechanisms: promising target against mycobacterium tuberculosis. Open Microbiol J 9:91–97CrossRefPubMedPubMedCentralGoogle Scholar
  28. Hickey TB, Ziltener HJ, Speert DP, Stokes RW (2010) Mycobacterium tuberculosis employs Cpn60.2 as an adhesin that binds CD43 on the macrophage surface. Cell Microbiol 12:1634–1647CrossRefPubMedGoogle Scholar
  29. Hunter RL, Armitige L, Jagannath C, Actor JK (2009) TB research at UT-Houston – a review of cord factor: new approaches to drugs, vaccines and the pathogenesis of tuberculosis. Tuberculosis (Edinb) 89:S18–S25CrossRefGoogle Scholar
  30. Kendall SL, Movahedzadeh F, Rison SC, Wernisch L, Parish T, Duncan K, Betts JC, Stoker NG (2004) The Mycobacterium tuberculosis dosRS two-component system is induced by multiple stresses. Tuberculosis (Edinb) 84:247–255CrossRefGoogle Scholar
  31. Kieser KJ, Rubin EJ (2014) How sisters grow apart: mycobacterial growth and division. Nat Rev. Microbiol. 12:550–562CrossRefPubMedGoogle Scholar
  32. Kinhikar AG, Vargas D, Li H, Mahaffey SB, Hinds L, Belisle JT, Laal S (2006) Mycobacterium tuberculosis malate synthase is a laminin-binding adhesin. Mol Microbiol 60:999–1013CrossRefPubMedGoogle Scholar
  33. Manganelli R, Proveddi R, Rodrigue S, Beaucher J, Gaudreau L, Smith I (2004) Sigma factors and global gene regulation in Mycobacterium tuberculosis. J Bacteriol 186:895–902CrossRefPubMedPubMedCentralGoogle Scholar
  34. Masaki T, Qu J, Cholewa-Waclaw J, Burr K, Raaum R, Rambukkana A (2013) Reprogramming adult Schwann cells to stem cell-like cells by leprosy bacilli promotes dissemination of infection. Cell 152:51–67CrossRefPubMedPubMedCentralGoogle Scholar
  35. Moraco AH, Kornfeld H (2014) Cell death and autophagy in tuberculosis. Semin Immunol 26:497–511CrossRefPubMedPubMedCentralGoogle Scholar
  36. Ng V, Zanazzi G, Timpl R, Talts JF, Salzer JL, Brennan PJ, Rambukkana A (2000) Role of the cell wall phenolic glycolipid-1 in the peripheral nerve predilection of Mycobacterium leprae. Cell 103:511–524CrossRefPubMedGoogle Scholar
  37. Ng VH, Cox JS, Sousa AO, MacMicking JD, McKinney JD (2004) Role of KatG catalase-peroxidase in mycobacterial pathogenesis: countering the phagocyte oxidative burst. Mol Microbiol 52:1291–1302CrossRefPubMedGoogle Scholar
  38. Perez E, Samper S, Bordas Y, Guilhot C, Gicquel B, Martın C (2001) An essential role for phoP in Mycobacterium tuberculosis virulence. Mol Microbiol 41:179–187CrossRefPubMedGoogle Scholar
  39. Pethe K, Bifani P, Drobecq H, Sergheraert C, Debrie A-S, Locht C, Menozzi FD (2002) Mycobacterial heparin-binding hemagglutinin and laminin-binding protein share antigenic methyllysines that confer resistance to proteolysis. Proc NatI Acad Sci USA 99:10759–10764CrossRefGoogle Scholar
  40. Prados-Rosales R, Baena A, Martinez LR, Luque-Garcia J, Kalscheuer R, Veeraraghavan U, Camara C, Nosanchuk JD, Besra GS, Chen B, Jimenez J, Glatman-Freedman A, Jacobs WR Jr, Porcelli SA, Casadevall A (2011) Mycobacteria release active membrane vesicles that modulate immune responses in a TLR2-dependent manner in mice. J Clin Investig 121:1471–1483CrossRefPubMedPubMedCentralGoogle Scholar
  41. Puech V, Guilhot C, Perez E, Tropis M, Armitige LY, Gicquel B, Daffé M (2002) Evidence for a partial redundancy of the fibronectin-binding proteins for the transfer of mycoloyl residues onto the cell wall arabinogalactan termini of Mycobacterium tuberculosis. Mol Microbiol 44:1109–1122CrossRefPubMedGoogle Scholar
  42. Ragas A, Roussel L, Puzo G, Riviere M (2007) The Mycobacterium tuberculosis cell-surface glycoprotein Apa as a potential adhesin to colonize target cells via the innate immune system pulmonary C-type lectin surfactant protein A. J Biol Chem 282:5133–5142CrossRefPubMedGoogle Scholar
  43. Rambukkana A, Yamada H, Zanazzi G, Mathus T, Salzer JL, Yurchenco PD, Campbell KP, Fischetti VA (1998) Role of alpha-dystroglycan as a Schwann cell receptor for Mycobacterium leprae. Science 282:2076–2079CrossRefPubMedGoogle Scholar
  44. Raynaud C, Guilhot C, Rauzier J, Bordat Y, Pelicic V, Manganelli R, Smith I, Gicquel B, Jackson M (2002) Phospholipases C are involved in the virulence of Mycobacterium tuberculosis. Mol Microbiol 45:203–217CrossRefPubMedGoogle Scholar
  45. Renshaw PS, Panagiotidou P, Whelan A, Gordon SV, Hewinson RG, Williamson RA, Carr MD (2002) Conclusive evidence that the major T-cell antigens of the mycobacterium tuberculosis complex ESAT-6 and CFP-10 form a tight, 1:1 complex and characterization of the structural properties of ESAT-6, CFP-10, and the ESAT-6*CFP-10 complex. Implications for pathogenesis and virulence. J Biol Chem 277:21598–21603CrossRefPubMedGoogle Scholar
  46. Roberts DM, Liao RP, Wisedchaisri G, Hol WG, Sherman DR (2004) Two sensor kinases contribute to the hypoxic response of Mycobacterium tuberculosis. J Biol Chem 279:23082–23087CrossRefPubMedPubMedCentralGoogle Scholar
  47. Roltgen K, Stinear TP, Pluschke G (2012) The genome, evolution and diversity of Mycobacterium ulcerans. Infect Genet Evol 12:522–529CrossRefPubMedGoogle Scholar
  48. Saini C, Tarique M, Rai R, Siddiqui A, Khanna N, Sharma A (2017) T helper cells in leprosy: an update. Immunol Lett 184:61–66CrossRefPubMedGoogle Scholar
  49. Samanovic MI, Darwin KH (2016) Game of ‘Somes: protein destruction for mycobacterium tuberculosis pathogenesis. Trends Microbiol 24:26–34CrossRefPubMedGoogle Scholar
  50. Sambandamurthy VK, Wang X, Chen B, Russell RG, Derrick S, Collins FM, Morris SL, Jacobs WR Jr (2002) A pantothenate auxotroph of Mycobacterium tuberculosis is highly attenuated and protects mice against tuberculosis. Nat Med 8:1171–1174CrossRefPubMedGoogle Scholar
  51. Sarfo FS, Phillips R, Wansbrough-Jones M, Simmonds RE (2016) Recent advances: role of mycolactone in the pathogenesis and monitoring of Mycobacterium ulcerans infection/Buruli ulcer disease. Cell Microbiol 18:17–29CrossRefPubMedGoogle Scholar
  52. Schwebach JR, Glatman-Freedman A, Gunther-Cummins L, Dai Z, Robbins JB, Schneerson R, Casadevall A (2002) Glucan is a component of the Mycobacterium tuberculosis surface that is expressed in vitro and in vivo. Infect Immun 70:2566–2575CrossRefPubMedPubMedCentralGoogle Scholar
  53. Sherman DR, Voskuil M, Schnappinger D, Liao R, Harrell MI, Schoolnik GK (2001) Regulation of the mycobacterium tuberculosis hypoxic response gene encoding alpha-crystallin. Proc NatI Acad Sci USA 98:7534–7539CrossRefGoogle Scholar
  54. Shimoji Y, Ng V, Matsumura K, Fischetti VA, Rambukkana A (1999) A 21-kDa surface protein of Mycobacterium leprae binds peripheral nerve laminin-2 and mediates Schwann cell invasion. Proc NatI Acad Sci USA 96:9857–9862CrossRefGoogle Scholar
  55. Smith I (2003) Mycobacterium tuberculosis pathogenesis and molecular determinants of virulence. Clin Microbiol Rev 16:463–496CrossRefPubMedPubMedCentralGoogle Scholar
  56. Stinear TP, Seemann T, Pidot S, Frigui W, Reysset G, Garnier T, Meurice G, Simon D, Bouchier C, Ma L, Tichit M, Porter JL, Ryan J, Johnson PD, Davies JK, Jenkin GA, Small PL, Jones LM, Tekaia F, Laval F, Daffe M, Parkhill J, Cole ST (2007) Reductive evolution and niche adaptation inferred from the genome of Mycobacterium ulcerans, the causative agent of Buruli ulcer. Genome Res 17:192–200CrossRefPubMedPubMedCentralGoogle Scholar
  57. Volkman HE, Pozos TC, Zheng J, Davis JM, Rawls JF, Ramakrishnan L (2009) Tuberculous granuloma induction via interaction of a bacterial secreted protein with host epithelium. Science 327:466–469CrossRefPubMedPubMedCentralGoogle Scholar
  58. Walburger A, Koul A, Ferrari G, Nguyen L, Prescianotto-Baschong C, Huygen K, Klebl B, Thompson C, Bacher G, Pieters J (2004) Protein kinase G from pathogenic Mycobacteria promotes survival within macrophages. Science 304:1800–1804CrossRefPubMedGoogle Scholar
  59. Zahrt TC, Wozniak C, Jones D, Trevett A (2003) Functional analysis of the Mycobacterium tuberculosis MprAB two-component signal transduction system. Infect Immun 71:6962–6970CrossRefPubMedPubMedCentralGoogle Scholar
  60. Zhang L, Zhang H, Zhao Y, Mao F, Wu J, Bai B, Xu Z, Jiang Y, Shi C (2012) Effects of Mycobacterium tuberculosis ESAT-6/CFP-10 fusion protein on the autophagy function of mouse macrophages. DNA Cell Biol 31:171–179CrossRefPubMedGoogle Scholar
  61. Zheng Q, Li Z, Zhou S, Zhang Q, Zhou L, Fu X, Yang L, Ma Y, Hao X (2017) Heparin-binding hemagglutinin of Mycobacterium tuberculosis is an inhibitor of autophagy. Front Cell Infect Microbiol 7:33PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Douglas I. Johnson
    • 1
  1. 1.Department of Microbiology & Molecular GeneticsUniversity of VermontBurlingtonUSA

Personalised recommendations