1887

Abstract

The incidence of complex (MAC) pulmonary disease (MAC PD), a refractory chronic respiratory tract infection, is increasing worldwide. MAC has three predominant colony morphotypes: smooth opaque (SmO), smooth transparent (SmT) and rough (Rg).

To determine whether colony morphotypes can predict the prognosis of MAC PD, we evaluated the virulence of SmO, SmT and Rg in mice and in human macrophages.

We compared the characteristics of mice and human macrophages infected with the SmO, SmT, or Rg morphotypes of subsp. 104. C57BL/6 mice and human macrophages derived from peripheral mononuclear cells were used in these experiments.

In comparison to SmO- or SmT-infected mice, Rg-infected mice revealed severe pathologically confirmed pneumonia, increased lung weight and increased lung bacterial burden. Rg-infected macrophages revealed significant cytotoxicity, increased bacterial burden, secretion of proinflammatory cytokines (TNF-α and IL-6) and chemokines (CCL5 and CCL3), and formation of cell clusters. Rg formed larger bacterial aggregates than SmO and SmT. Cytotoxicity, bacterial burden and secretion of IL-6, CCL5 and CCL3 were induced strongly by Rg infection, and were decreased by disaggregation of the bacteria.

Rg, which is associated with bacterial aggregation, has the highest virulence among the predominant colony morphotypes.

Funding
This study was supported by the:
  • Takeda Science Foundation
    • Principle Award Recipient: Tomoyasu Nishimura
  • Waksman Foundation of Japan
    • Principle Award Recipient: Tomoyasu Nishimura
  • Japan Society for the Promotion of Science (Award 19K08936)
    • Principle Award Recipient: Tomoyasu Nishimura
  • Japan Society for the Promotion of Science (Award 16K09942)
    • Principle Award Recipient: Tomoyasu Nishimura
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/content/journal/jmm/10.1099/jmm.0.001224
2020-06-26
2024-03-28
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References

  1. Prevots DR, Marras TK. Epidemiology of human pulmonary infection with nontuberculous mycobacteria: a review. Clin Chest Med 2015; 36:13–34 [View Article][PubMed]
    [Google Scholar]
  2. Henkle E, Hedberg K, Schafer S, Novosad S, Winthrop KL. Population-Based incidence of pulmonary nontuberculous mycobacterial disease in Oregon 2007 to 2012. Ann Am Thorac Soc 2015; 12:642–647 [View Article][PubMed]
    [Google Scholar]
  3. Morimoto K, Hasegawa N, Izumi K, Namkoong H, Uchimura K et al. A laboratory-based analysis of nontuberculous mycobacterial lung disease in Japan from 2012 to 2013. Ann Am Thorac Soc 2017; 14:49–56 [View Article][PubMed]
    [Google Scholar]
  4. Belisle JT, McNeil MR, Chatterjee D, Inamine JM, Brennan PJ. Expression of the core lipopeptide of the glycopeptidolipid surface antigens in rough mutants of Mycobacterium avium. J Biol Chem 1993; 268:10510–10516[PubMed]
    [Google Scholar]
  5. Torrelles JB, Ellis D, Osborne T, Hoefer A, Orme IM et al. Characterization of virulence, colony morphotype and the glycopeptidolipid of Mycobacterium avium strain 104. Tuberculosis 2002; 82:293–300 [View Article][PubMed]
    [Google Scholar]
  6. Schaefer WB, Davis CL, Cohn ML. Pathogenicity of transparent, opaque, and rough variants of Mycobacterium avium in chickens and mice. Am Rev Respir Dis 1970; 102:499–506 [View Article][PubMed]
    [Google Scholar]
  7. Pedrosa J, Flórido M, Kunze ZM, Castro AG, Portaels F et al. Characterization of the virulence of Mycobacterium avium complex (MAC) isolates in mice. Clin Exp Immunol 1994; 98:210–216 [View Article][PubMed]
    [Google Scholar]
  8. Howard ST, Rhoades E, Recht J, Pang X, Alsup A et al. Spontaneous reversion of Mycobacterium abscessus from a smooth to a rough morphotype is associated with reduced expression of glycopeptidolipid and reacquisition of an invasive phenotype. Microbiology 2006; 152:1581–1590 [View Article][PubMed]
    [Google Scholar]
  9. Brambilla C, Llorens-Fons M, Julián E, Noguera-Ortega E, Tomàs-Martínez C et al. Mycobacteria clumping increase their capacity to damage macrophages. Front Microbiol 2016; 7:1562 [View Article][PubMed]
    [Google Scholar]
  10. Fujita Y, Doi T, Maekura R, Ito M, Yano I. Differences in serological responses to specific glycopeptidolipid-core and common lipid antigens in patients with pulmonary disease due to Mycobacterium tuberculosis and Mycobacterium avium complex. J Med Microbiol 2006; 55:189–199 [View Article][PubMed]
    [Google Scholar]
  11. Shimoda M, Yoshida H, Mizuno S, Hirozane T, Horiuchi K et al. Hyaluronan-Binding protein involved in hyaluronan depolymerization controls endochondral ossification through hyaluronan metabolism. Am J Pathol 2017; 187:1162–1176 [View Article][PubMed]
    [Google Scholar]
  12. Nishimura T, Tamizu E, Uno S, Uwamino Y, Fujiwara H et al. hsa-miR-346 is a potential serum biomarker of Mycobacterium avium complex pulmonary disease activity. J Infect Chemother 2017; 23:703–708 [View Article][PubMed]
    [Google Scholar]
  13. Nishimura T, Zhao X, Gan H, Koyasu S, Remold HG. The prostaglandin E2 receptor EP4 is integral to a positive feedback loop for prostaglandin E2 production in human macrophages infected with Mycobacterium tuberculosis. Faseb J 2013; 27:3827–3836 [View Article][PubMed]
    [Google Scholar]
  14. Dong H, Lv Y, Sreevatsan S, Zhao D, Zhou X. Differences in pathogenicity of three animal isolates of Mycobacterium species in a mouse model. PLoS One 2017; 12:e0183666 [View Article][PubMed]
    [Google Scholar]
  15. Gupta UD, Katoch VM. Animal models of tuberculosis. Tuberculosis 2005; 85:277–293 [View Article][PubMed]
    [Google Scholar]
  16. Nikonenko BV, Apt AS. Drug testing in mouse models of tuberculosis and nontuberculous mycobacterial infections. Tuberculosis 2013; 93:285–290 [View Article][PubMed]
    [Google Scholar]
  17. McClean CM, Tobin DM, form M. Macrophage form, function, and phenotype in mycobacterial infection: lessons from tuberculosis and other diseases. Pathog Dis 2016; 74:ftw068 [View Article][PubMed]
    [Google Scholar]
  18. Orme IM, Cooper AM. Cytokine/Chemokine cascades in immunity to tuberculosis. Immunol Today 1999; 20:307–312 [View Article][PubMed]
    [Google Scholar]
  19. Welsh KJ, Abbott AN, Hwang S-A, Indrigo J, Armitige LY et al. A role for tumour necrosis factor-alpha, complement C5 and interleukin-6 in the initiation and development of the mycobacterial cord factor trehalose 6,6'-dimycolate induced granulomatous response. Microbiology 2008; 154:1813–1824 [View Article][PubMed]
    [Google Scholar]
  20. Bhatnagar S, Schorey JS. Elevated mitogen-activated protein kinase signalling and increased macrophage activation in cells infected with a glycopeptidolipid-deficient Mycobacterium avium. Cell Microbiol 2006; 8:85–96 [View Article][PubMed]
    [Google Scholar]
  21. Schorey JS, Sweet L. The mycobacterial glycopeptidolipids: structure, function, and their role in pathogenesis. Glycobiology 2008; 18:832–841 [View Article][PubMed]
    [Google Scholar]
  22. Belisle JT, Klaczkiewicz K, Brennan PJ, Jacobs WR, Inamine JM. Rough morphological variants of Mycobacterium avium. Characterization of genomic deletions resulting in the loss of glycopeptidolipid expression. J Biol Chem 1993; 268:10517–10523[PubMed]
    [Google Scholar]
  23. Eckstein TM, Belisle JT, Inamine JM. Proposed pathway for the biosynthesis of serovar-specific glycopeptidolipids in Mycobacterium avium serovar 2. Microbiology 2003; 149:2797–2807 [View Article][PubMed]
    [Google Scholar]
  24. Rhoades ER, Archambault AS, Greendyke R, Hsu F-F, Streeter C et al. Mycobacterium abscessus glycopeptidolipids mask underlying cell wall phosphatidyl-myo-inositol mannosides blocking induction of human macrophage TNF-alpha by preventing interaction with TLR2. J Immunol 2009; 183:1997–2007 [View Article][PubMed]
    [Google Scholar]
  25. Balcewicz-Sablinska MK, Gan H, Remold HG. Interleukin 10 produced by macrophages inoculated with Mycobacterium avium attenuates mycobacteria-induced apoptosis by reduction of TNF-alpha activity. J Infect Dis 1999; 180:1230–1237 [View Article][PubMed]
    [Google Scholar]
  26. Etienne G, Villeneuve C, Billman-Jacobe H, Astarie-Dequeker C, Dupont M-A et al. The impact of the absence of glycopeptidolipids on the ultrastructure, cell surface and cell wall properties, and phagocytosis of Mycobacterium smegmatis . Microbiology 2002; 148:3089–3100 [View Article][PubMed]
    [Google Scholar]
  27. Borrego S, Niubó E, Ancheta O, Espinosa ME. Study of the microbial aggregation in Mycobacterium using image analysis and electron microscopy. Tissue Cell 2000; 32:494–500 [View Article][PubMed]
    [Google Scholar]
  28. Pang L, Tian X, Pan W, Xie J. Structure and function of Mycobacterium glycopeptidolipids from comparative genomics perspective. J Cell Biochem 2013; 114:1705–1713 [View Article][PubMed]
    [Google Scholar]
  29. Kansal RG, Gomez-Flores R, Mehta RT. Change in colony morphology influences the virulence as well as the biochemical properties of the Mycobacterium avium complex. Microb Pathog 1998; 25:203–214 [View Article][PubMed]
    [Google Scholar]
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