Advertisement

Applied Microbiology and Biotechnology

, Volume 100, Issue 9, pp 3887–3892 | Cite as

Functions and importance of mycobacterial extracellular vesicles

  • G. Marcela RodriguezEmail author
  • Rafael Prados-Rosales
Mini-Review

Abstract

The release of cellular factors by means of extracellular vesicles (EVs) is conserved in archaea, bacteria, and eukaryotes. EVs are released by growing bacteria as part of their interaction with their environment and, for pathogenic bacteria, constitute an important component of their interactions with the host. While EVs released by gram-negative bacteria have been extensively studied, the vesicles released by thick cell wall microorganisms like mycobacteria were recognized only recently and are less well understood. Nonetheless, studies of mycobacterial EVs have already suggested roles in pathogenesis, opening exciting new avenues of research aimed at understanding their biogenesis and potential use in antitubercular strategies. In this minireview, we discuss the discovery of mycobacterial vesicles, the current understanding of their nature, content, regulation, and possible functions, as well as their potential therapeutic applications.

Keywords

Mycobacterium Vesicles Siderophores Iron Lipoproteins Vaccines 

Notes

Acknowledgments

RP’s work discussed here was supported by a grant from the Bill and Melinda Gates Foundation. GMR’s work discussed here was supported by the National Institutes of Health grant AI044856. The authors thank Erika Shor for help in manuscript preparation.

Compliance with ethical standards

All procedures with Mtb-infected animals conducted by the authors and mentioned in this review were approved by the Albert Einstein College of Medicine animal care and use committee.

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Acevedo R, Fernandez S, Zayas C, Acosta A, Sarmiento ME, Ferro VA, Rosenqvist E, Campa C, Cardoso D, Garcia L, Perez JL (2014) Bacterial outer membrane vesicles and vaccine applications. Front Immunol 5:121CrossRefPubMedPubMedCentralGoogle Scholar
  2. Basaraba RJ, Bielefeldt-Ohmann H, Eschelbach EK, Reisenhauer C, Tolnay AE, Taraba LC, Shanley CA, Smith EA, Bedwell CL, Chlipala EA, Orme IM (2008) Increased expression of host iron-binding proteins precedes iron accumulation and calcification of primary lung lesions in experimental tuberculosis in the Guinea pig. Tuberculosis (Edinb) 88:69–79CrossRefGoogle Scholar
  3. Cairo G, Recalcati S, Mantovani A, Locati M (2011) Iron trafficking and metabolism in macrophages: contribution to the polarized phenotype. Trends Immunol 32:241–247CrossRefPubMedGoogle Scholar
  4. Ciofu O, Beveridge TJ, Kadurugamuwa J, Walther-Rasmussen J, Hoiby N (2000) Chromosomal beta-lactamase is packaged into membrane vesicles and secreted from Pseudomonas aeruginosa. J Antimicrob Chemother 45:9–13CrossRefPubMedGoogle Scholar
  5. Daffe M (2015) The cell envelope of tubercle bacilli. Tuberculosis (Edinb) 95(Suppl 1):S155–S158CrossRefGoogle Scholar
  6. De Voss JJ, Rutter K, Schroeder BG, Su H, Zhu Y, III BCE (2000) The salicylate-derived mycobactin siderophores of Mycobacterium tuberculosis are essential for growth in macrophages. Proc Natl Acad Sci 97:1252–1257CrossRefPubMedPubMedCentralGoogle Scholar
  7. Gobin J, Horwitz M (1996) Exochelins of Mycobacterium tuberculosis remove iron from human iron-binding proteins and donate iron to mycobactins in the M. tuberculosis cell wall. J Exp Med 183:1527–1532CrossRefPubMedGoogle Scholar
  8. Gobin J, Moore CH, Reeve JR Jr, Wong DK, Gibson BW, Horwitz MA (1995) Iron acquisition by Mycobacterium tuberculosis: Isolation and characterization of a family of iron-binding exochelins. Proc Natl Acad Sci U S A 92:5189–5193CrossRefPubMedPubMedCentralGoogle Scholar
  9. Gurung M, Moon DC, Choi CW, Lee JH, Bae YC, Kim J, Lee YC, Seol SY, Cho DT, Kim SI, Lee JC (2011) Staphylococcus aureus Produces membrane-derived vesicles that induce host cell death. PLoS one 6:e27958CrossRefPubMedPubMedCentralGoogle Scholar
  10. Hoekstra D, van der Laan JW, de Leij L, Witholt B (1976) Release of outer membrane fragments from normally growing Escherichia coli. Biochim Biophys Acta 455:889–899CrossRefPubMedGoogle Scholar
  11. Holmes MA, Paulsene W, Jide X, Ratledge C, Strong RK (2005) Siderocalin (Lcn 2) also binds carboxymycobactins, potentially defending against mycobacterial infections through iron sequestration. Structure 13:29–41CrossRefPubMedGoogle Scholar
  12. Kesty NC, Kuehn MJ (2004) Incorporation of heterologous outer membrane and periplasmic proteins into Escherichia coli outer membrane vesicles. J Biol Chem 279:2069–2076CrossRefPubMedPubMedCentralGoogle Scholar
  13. Kolling GL, Matthews KR (1999) Export of virulence genes and Shiga toxin by membrane vesicles of Escherichia coli O157:H7. Appl Environ Microbiol 65:1843–1848PubMedPubMedCentralGoogle Scholar
  14. Kuehn MJ, Kesty NC (2005) Bacterial outer mebrane vesicles and the host-pathogen interactions. Genes Dev 19:2645–2655CrossRefPubMedGoogle Scholar
  15. Lee EY, Choi DY, Kim DK, Kim JW, Park JO, Kim S, Kim SH, Desiderio DM, Kim YK, Kim KP, Gho YS (2009) Gram-positive bacteria produce membrane vesicles: proteomics-based characterization of Staphylococcus aureus-derived membrane vesicles. Proteomics 9:5425–5436CrossRefPubMedGoogle Scholar
  16. Litwin CM, Calderwood SB (1993) Role of iron in regulation of virulence genes. Clin Microbiol Rev 6:137–149PubMedPubMedCentralGoogle Scholar
  17. Luo M, Fadeev Evgeny A, Groves JT (2005) Mycobactin-mediated iron acquisition within macrophages. Nat Chem Biol 1:149–153CrossRefPubMedGoogle Scholar
  18. Marsollier L, Brodin P, Jackson M, Kordulakova J, Tafelmeyer P, Carbonnelle E, Aubry J, Milon G, Legras P, Andre JP, Leroy C, Cottin J, Guillou ML, Reysset G, Cole ST (2007) Impact of Mycobacterium ulcerans biofilm on transmissibility to ecological niches and Buruli ulcer pathogenesis. PLoS Pathog 3:e62CrossRefPubMedPubMedCentralGoogle Scholar
  19. Prados-Rosales R, Carreno LJ, Batista-Gonzalez A, Baena A, Venkataswamy MM, Xu J, Yu X, Wallstrom G, Magee DM, LaBaer J, Achkar JM, Jacobs WR Jr, Chan J, Porcelli SA, Casadevall A (2014a) Mycobacterial membrane vesicles administered systemically in mice induce a protective immune response to surface compartments of Mycobacterium tuberculosis. MBio 5:e01921–e01914CrossRefPubMedPubMedCentralGoogle Scholar
  20. Prados-Rosales R, Weinrick B, Piqué D, Jacobs WR Jr, Casadevall A, Rodriguez GM (2014b) Role for Mycobacterium tuberculosis membrane vesicles in iron acquistion. J Bacteriol 196:1250–1256CrossRefPubMedPubMedCentralGoogle Scholar
  21. 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 Invest 121:1471–1483CrossRefPubMedPubMedCentralGoogle Scholar
  22. Rath P, Huang C, Wang T, Wang T, Li H, Prados-Rosales R, Elemento O, Casadevall A, Nathan CF (2013) Genetic regulation of vesiculogenesis and immunomodulation in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A 110:E4790–E4797CrossRefPubMedPubMedCentralGoogle Scholar
  23. Ratledge C, Dover LG (2000) Iron metabolism in pathogenic bacteria. Annu Rev Microbiol 54:881–941CrossRefPubMedGoogle Scholar
  24. Reddy P.V., R.V. Puri, P. Chauhan, R. Kar, A. Rohilla, A. Khera & A.K. Tyagi (2013) Disruption of mycobactin biosynthesis leads to attenuation of Mycobacterium tuberculosis for growth and virulence. J Infect Dis 208:1255–1265Google Scholar
  25. Rodriguez GM, Smith I (2006) Identification of an ABC transporter required for iron acquisition and virulence in Mycobacterium tuberculosis. J Bacteriol 168:424–430Google Scholar
  26. Ryndak M, Wang S, Smith. I, Rodriguez GM (2010) The Mycobacterium tuberculosis high-affinity iron importer, IrtA, contains an FAD-binding domain. J. Bacteriology 192:861–869CrossRefGoogle Scholar
  27. Snow GA (1970) Mycobactins: iron chelating growth factors from mycobacteria. Bacteriol Rev 34:99–125PubMedPubMedCentralGoogle Scholar
  28. Snow GA, White AJ (1969) Chemical and biological properties of mycobactins isolated from various mycobacteria. Biochem J 115:1031–1045CrossRefPubMedPubMedCentralGoogle Scholar
  29. Weinberg ED (1984) Iron withholding: a defense against infection and neoplasia. Physiol Rev 64:65–102PubMedGoogle Scholar
  30. Ziegenbalg A, Prados-Rosales R, Jenny-Avital ER, Kim RS, Casadevall A, Achkar JM (2013) Immunogenicity of mycobacterial vesicles in humans: identification of a new tuberculosis antibody biomarker. Tuberculosis (Edinb) 93:448–455CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  1. 1.Public Health Research Institute Center and New Jersey Medical School–Rutgers, The State University of New JerseyNewarkUSA
  2. 2.Department of Microbiology and ImmunologyAlbert Einstein College of MedicineBronxUSA
  3. 3.Infectious Diseases ProgramCIC bioGUNEDerioSpain

Personalised recommendations