Quorum Sensing in Mycobacterium Tuberculosis: Its Role in Biofilms and Pathogenesis

  • Devanabanda Mallaiah
  • Pallaval Veera Bramhachari


Quorum sensing signaling molecules also called auto-inducers secretes from bacteria into its immediate extracellular environment and the molecules are concentrated as their bacterial population increases. At certain threshold concentration, auto-inducers regulate the expression of different types of genes and phenotypes, which includes virulence and formation of bio-films. Bio-films are responsible for 65% of bacterial infections. Mycobacterium tuberculosis (Mtb) causes one of the infectious disease named as tuberculosis (TB), infected one-third of world’s population. In humans, following primary TB infection, Mtb enters into latent stage. Reactivation or re-infection by new Mtb soften and fragments the lung tissue leaving cavities. The success of Mtb comes from its ability to grow as pellicle, a bio-film like structure on the surface of such cavities. The Mtb bio-films are highly resistant to drugs and implicated in persistence. The presence of LuxR homologs and expression patterns of transcription regulator, WhiB3 suggests quorum sensing existence in Mtb. The involvement of nucleotide-based second messengers such as c-di-GMP in signal transduction gives another indirect evidence of quorum sensing mechanisms in Mtb. The present chapter reviews quorum sensing mechanisms and their importance in bio-film formation, regulation of gene expressions, virulence and pathogenesis of Mtb, which will provide basis for novel anti-tuberculosis therapy.


Quorum sensing Virulence Mycobacterium tuberculosis Pathogenesis Bio-film 


  1. 1.
    Cambier, C. J., Falkow, S., & Ramakrishnan, L. (2014). Host evasion and exploitation schemes of Mycobacterium tuberculosis. Cell, 159(7), 1497–1509.CrossRefGoogle Scholar
  2. 2.
    Kenneth, J. R., & Ray, C. G. (2004). Mycobacteria. Sherris medical microbiology: An introduction to infectious diseases (4th ed.p. 439). New York: McGraw-Hill ISBN 0-83-858529-9.Google Scholar
  3. 3.
    Mukherjee, K., Tribedi, P., Mukhopadhyay, B., & Sil, A. K. (2013). Antibacterial activity of long-chain fatty alcohols against mycobacteria. FEMS Microbiology Letters, 338(2), 177–183.CrossRefGoogle Scholar
  4. 4.
    Kaufmann, G. F., Park, J., & Janda, K. D. (2008). Bacterial quorum sensing: A new target for anti-infective immunotherapy. Expert Opinion on Biological Therapy, 8(6), 719–724.CrossRefGoogle Scholar
  5. 5.
    Brackman, G., Cos, P., Maes, L., Nelis, H. J., & Coenye, T. (2011). Quorum sensing inhibitors increase the susceptibility of bacterial biofilms to antibiotics in vitro and in vivo. Antimicrobial Agents and Chemotherapy, 55(6), 2655–2661.CrossRefGoogle Scholar
  6. 6.
    Polkade, A. V., Mantri, S. S., Patwekar, U. J., & Jangid, K. (2016). Quorum sensing: An under-explored phenomenon in the phylum actinobacte. Frontiers in Microbiology, 7, 131.CrossRefGoogle Scholar
  7. 7.
    LaSarre, B., & Federle, M. J. (2013). Exploiting quorum sensing to confuse bacterial pathogens. Microbiology and Molecular Biology Reviews, 77(1), 73–111.CrossRefGoogle Scholar
  8. 8.
    Deep, A., Chaudhary, U., & Gupta, V. (2011). Quorum sensing and bacterial pathogenicity: From molecules to disease. Journal of Laboratory and Physicians, 3(1), 4–11.CrossRefGoogle Scholar
  9. 9.
    Chen, J., & Xie, J. (2011). Role and regulation of bacterial LuxR-like regulators. Journal of Cellular Biochemistry, 112(10), 2694–2702.CrossRefGoogle Scholar
  10. 10.
    Banaiee, N., Jacobs, W. R., Jr., & Ernst, J. D. (2006). Regulation of Mycobacterium tuberculosis whiB3 in the mouse lung and macrophages. Infection and Immunity, 74(11), 6449–6457.CrossRefGoogle Scholar
  11. 11.
    Sharma, I. M., Petchiappan, A., & Chatterji, D. (2014). Quorum sensing and biofilm formation in mycobacteria: Role of c-di-GMP and methods to study this second messenger. IUBMB Life, 66(12), 823–834.CrossRefGoogle Scholar
  12. 12.
    de la Fuente-Núñez, C., Reffuveille, F., Fernández, L., & Hancock, R. E. (2013). Bacterial biofilm development as a multicellular adaptation: Antibiotic resistance and new therapeutic strategies. Current Opinion in Microbiology, 16(5), 580–589.CrossRefGoogle Scholar
  13. 13.
    O’Toole, G., Kaplan, H. B., & Kolter, R. (2000). Biofilm formation as microbial development. Annual Review of Microbiology, 54, 49–79.CrossRefGoogle Scholar
  14. 14.
    Beloin, C., & Ghigo, J. M. (2005). Finding gene-expression patterns in bacterial biofilms. Trends in Microbiology, 13(1), 16–19.CrossRefGoogle Scholar
  15. 15.
    Hunter, R. L., Actor, J. K., Hwang, S. A., Karev, V., & Jagannath, C. (2014). Pathogenesis of post primary tuberculosis: Immunity and hypersensitivity in the development of Cavities. Annals of Clinical and Laboratory Science, 44(4), 365–387.PubMedGoogle Scholar
  16. 16.
    Ojha, A. K., Baughn, A. D., Sambandan, D., Hsu, T., Trivelli, X., Guerardel, Y., Alahari, A., Kremer, L., Jacobs, W. R., Jr., & Hatfull, G. F. (2008). Growth of Mycobacterium tuberculosis biofilms containing free mycolic acids and harbouring drug-tolerant bacteria. Molecular Microbiology, 69(1), 164–174.CrossRefGoogle Scholar
  17. 17.
    Pang, J. M., Layre, E., Sweet, L., Sherrid, A., Moody, D. B., Ojha, A., & Sherman, D. R. (2012). The polyketide Pks1 contributes to biofilm formation in Mycobacterium tuberculosis. Journal of Bacteriology, 194(3), 715–721.CrossRefGoogle Scholar
  18. 18.
    Wolff, K. A., de la Peña, A. H., Nguyen, H. T., Pham, T. H., Amzel, L. M., Gabelli, S. B., & Nguyen, L. (2015). A redox regulatory system critical for mycobacterial survival in macrophages and biofilm development. PLoS Pathogens, 11(4), e1004839.CrossRefGoogle Scholar
  19. 19.
    Sambandan, D., Dao, D. N., Weinrick, B. C., Vilchèze, C., Gurcha, S. S., Ojha, A., Kremer, L., Besra, G. S., Hatfull, G. F., & Jacobs, W. R., Jr. (2013). Keto-mycolic acid-dependent pellicle formation confers tolerance to drug-sensitive Mycobacterium tuberculosis. MBio, 4(3), e00222–e00213.CrossRefGoogle Scholar
  20. 20.
    Johansen, T. B., Agdestein, A., Olsen, I., Nilsen, S. F., Holstad, G., & Djønne, B. (2009). Biofilm formation by Mycobacterium avium isolates originating from humans, swine and birds. BMC Microbiology, 9, 159.CrossRefGoogle Scholar
  21. 21.
    Mwambete, K. D. (2015). Targeting microbial virulence factors: potential alternative to evade the antimicrobial resistance threats. ©Formatex. Strategies, 4, 5.Google Scholar
  22. 22.
    Glickman, M. S., & Jacobs, W. R. (2001). Microbial pathogenesis of Mycobacterium tuberculosis: Dawn of a discipline. Cell, 104(4), 477–485.CrossRefGoogle Scholar
  23. 23.
    Manabe, Y. C., Saviola, B. J., Sun, L., Murphy, J. R., & Bishai, W. R. (1999.;26). Attenuation of virulence in Mycobacterium tuberculosis expressing a constitutively active iron repressor. Proceedings of the National Academy of Sciences of the United States of America, 96(22), 12844–12848.CrossRefGoogle Scholar
  24. 24.
    Bharati, B. K., & Chatterji, D. (2013). Quorum sensing and pathogenesis: Role of small signalling molecules in bacterial persistence. Current Science, 105(5), 10 september.Google Scholar
  25. 25.
    Rickman, L., Scott, C., Hunt, D. M., Hutchinson, T., Menéndez, M. C., Whalan, R., Hinds, J., Colston, M. J., Green, J., & Buxton, R. S. (2005). A member of the cAMP receptor protein family of transcription regulators in Mycobacterium tuberculosis is required for virulence in mice and controls transcription of the rpfA gene coding for a resuscitation promoting factor. Molecular Microbiology, 56(5), 1274–1286.CrossRefGoogle Scholar
  26. 26.
    Rutherford, S. T., & Bassler, B. L. (2012). Bacterial quorum sensing: Its role in virulence and possibilities for its control. Cold Spring Harbor Perspectives in Medicine, 2(11), a012427.CrossRefGoogle Scholar
  27. 27.
    Slama, N., Jamet, S., Frigui, W., Pawlik, A., Bottai, D., Laval, F., Constant, P., Lemassu, A., Cam, K., Daffé, M., Brosch, R., Eynard, N., & Quémard, A. (2016). The changes in mycolic acid structures caused by hadC mutation have a dramatic effect on the virulence of Mycobacterium tuberculosis. Molecular Microbiology, 99(4), 794–807.CrossRefGoogle Scholar
  28. 28.
    Fang, H., Yu, D., Hong, Y., Zhou, X., Li, C., & Sun, B. (2013). The LuxR family regulator Rv0195 modulates Mycobacterium tuberculosis dormancy and virulence. Tuberculosis (Edinburgh, Scotland), 93(4), 425–431.CrossRefGoogle Scholar

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© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Devanabanda Mallaiah
    • 1
  • Pallaval Veera Bramhachari
    • 2
  1. 1.Department of Biotechnology and BioinformaticsYogi vemana UniversityKadapaIndia
  2. 2.Department of BiotechnologyKrishna UniversityMachilipatnamIndia

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