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Mycobacterial infections: Molecular characterisation of the pathogens and the immune response of the host

Principal investigators: Astrid Lewin and Hubert Schäfer

The genus Mycobacterium (M.) includes important bacterial pathogens such as the causative agent of tuberculosis, M. tuberculosis or the leprosy pathogen, M. leprae. The mycobacteria also comprise more than 100 bacterial species which are termed nontuberculous mycobacteria (NTM) and can cause serious diseases, such as pulmonary infections, lymphadenitis in small children as well as skin, soft tissue and joint infections. The most important NTM pathogen in Germany is M. avium subsp. hominissuis, which can cause serious infections in particular in immunodeficient persons such as AIDS-patients. Another problematic pathogen is M. abscessus. This bacterium often causes lung infections in patients with cystic fibrosis that are extremely hard to treat.

Pathogenic mycobacteria are characterised by their ability to survive and multiply in macrophages. Furthermore, some of them are able to induce the formation of granulomas. These are structured aggregates of immune cells which limit the multiplication and dissemination of the bacteria. Within these granulomas mycobacteria can survive in a state of latency. In most industrial countries the number of infections with tuberculous mycobacteria has been decreasing over the last decades; the number of diseases caused by NTM however, seems to increase. For that reason there is a considerable need for research both on the pathogenicity of these bacteria and on the improvement of diagnostic and therapeutic approaches targeting these infections.

Within the scope of this project the mechanisms of action which allow mycobacteria to escape the defence mechanisms of the immune system are to be identified and characterised. To do so, we compare the genetic structure of different pathogens, identify virulence genes and investigate their impact on the interaction with host cells. A focus of our work is the characterization of the species M. avium and M. abscessus causing hardy lung infections especially in immune-compromised persons and in patients with cystic fibrosis.

On the other side of the interaction between pathogens and the host we try to identify and characterise the immune mechanisms which act at the defence against mycobacterial infections. In this context the immune reactions caused by an M. avium infection will be characterised. In parallel, the effector mechanisms are to be identified which impart a certain degree of protection against infections by mycobacteria after immunisation with the vaccine strain BCG (Bacille Calmette Guérin).

In a further approach we try to specifically identify the proteins of Mycobacterium avium hominissuis which trigger an immune response during an infection, i.e. act as immunodominant antigens. Knowledge about these antigens can contribute to an improvement of diagnostic measures or to developing new vaccines.


Elisabeth Kamal, Gudrun Kliem, Barbara Kropp, Petra Matzk, Greana Kirubakar, Suriya Akter


  • Isolation and characterization of NTM isolated from patients with cystic fibrosis
  • Comparative analysis of the genome structure of M. avium isolates and M. abscessus isolates from patients and the environment
  • Investigation of the interaction of different M. avium and M. abscessus isolates with human cells
  • Isolation and characterisation of new virulence factors of M. avium and M. abscessus
  • Investigation of the role of selected latency-associated genes of M. bovis BCG for the interaction with human cells
  • Identification of immunogenic proteins from M. avium
  • Characterisation of effector mechanisms at the immune response against mycobacteria

Date: 14.11.2018


  • Murugaiyan J, Lewin A, Kamal E et al. (2018): MALDI spectra database for rapid discrimination and subtyping of Mycobacterium kansasii.
    Front. Microbiol. 9 (Apr): 587. Epub Apr 3. doi: 10.3389/fmicb.2018.00587. more

  • Kirubakar G, Murugaiyan J, Schaudinn C, Dematheis F, Holland G, Eravci M, Weise C, Roesler U, Lewin A (2018): Proteome analysis of an M. avium mutant exposes a novel role of the bifunctional protein LysX in regulation of metabolic activity.
    J. Infect. Dis. 218 (2): 291–299. Epub Feb 19. doi: 10.1093/infdis/jiy100. more

  • Shoulah SA, Oschmann AM, Selim A, Semmler T, Schwarz C, Kamal E, Hamouda F, Galila E, Bitter W, Lewin A (2018): Environmental Mycobacterium avium subsp. hominissuis have a higher probability to act as a recipient in conjugation than clinical strains.
    Plasmid 95: 28-35. Epub Jan 14. doi: 10.1016/j.plasmid.2018.01.003. more

  • Sanchini A, Dematheis F, Semmler T, Lewin A (2017): Metabolic phenotype of clinical and environmental Mycobacterium avium subsp. hominissuis isolates.
    Peer J. 5: e2833. Epub Jan 3. doi: 10.7717/peerj.2833. more

  • Sanchini A, Semmler T, Mao L, Kumar N, Dematheis F, Tandon K, Peddireddy V, Ahmed N, Lewin A (2016): A hypervariable genomic island identified in clinical and environmental Mycobacterium avium subsp. hominissuis isolates from Germany.
    Int. J. Med. Microbiol. 306 (7): 495-503. Epub Jul 18. doi: 10.1016/j.ijmm.2016.07.001. more

  • Lahiri A, Sanchini A, Semmler T, Schäfer H, Lewin A (2014): Identification and comparative analysis of a genomic island in Mycobacterium avium subsp. hominissuis.
    FEBS Letters 588 (21): 3906–3911. Epub Sep 12. doi: 10.1016/j.febslet.2014.08.037. more

  • Lahiri A, Kneisel J, Kloster I, Kamal E, Lewin A (2014): Abundance of Mycobacterium avium ssp. hominissuis in soil and dust in Germany – implications for the infection route.
    Lett. Appl. Microbiol. 59 (1): 65-70. Epub Mar 10. doi: 10.1111/lam.12243. more

  • Kolb J, Hillemann D, Möbius P, Reetz J, Lahiri A, Lewin A et al. (2014): Genetic characterization of German Mycobacterium avium strains isolated from different hosts and specimens by multilocus sequence typing.
    Int. J. Med. Microbiol. 304 (8): 941–948. Epub Jun 28. doi: 10.1016/j.ijmm.2014.06.001. more

  • Coscolla M, Lewin A, Metzger S, Mätz-Rensing K, Calvignac-Spencer S, Nitsche A, Dabrowski PW, Radonić A, Niemann S, Parkhill J, Couacy-Hymann E, Feldman J, Comas I, Boesch C, Gagneux S, Leendertz FH (2013): Novel Mycobacterium tuberculosis Complex Isolate from a Wild Chimpanzee.
    Emerg. Infect. Dis. 19 (6): 969–976. doi: 10.3201/eid1906.121012. more

  • Kumar A, Lewin A, Rani PS, Qureshi IA, Devi S, Majid M, Kamal E, Marek S et al. (2013): Dormancy Associated Translation Inhibitor (DATIN/Rv0079) of Mycobacterium tuberculosis interacts with TLR2 and induces proinflammatory cytokine expression.
    Cytokine 64 (1): 258–264. Epub Jun 29. doi: 10.1016/j.cyto.2013.06.310. more

  • Khattak FA, Kumar A, Kamal E, Kunisch R, Lewin A (2012): Illegitimate recombination: An efficient method for random mutagenesis in Mycobacterium avium subsp. hominissuis.
    BMC Microbiology 12: 204. Epub Sept 11. doi: 10.1186/1471-2180-12-204. more

  • Kunisch R, Kamal E, Lewin A (2012): The role of the mycobacterial DNA-binding protein 1 (MDP1) from Mycobacterium bovis BCG in host cell interaction.
    BMC Microbiology 12: 165. doi: 10.1186/1471-2180-12-165. more

  • Kumar A, Majid M, Kunisch R, Rani PS, Qureshi IA, Lewin A et al. (2012): Mycobacterium tuberculosis DosR Regulon Gene Rv0079 Encodes a Putative, 'Dormancy Associated Translation Inhibitor (DATIN)'.
    PLoS One 7 (6): e38709. Epub Jun 13. more

  • Niki M, Niki M, Tateishi Y, Ozeki Y, Kirikae T, Lewin A et al. (2012): A novel mechanism of growth phase-dependent tolerance to isoniazid in mycobacteria.
    J. Biol. Chem. 287 (33): 27743-27752. Epub May 30. DOI 10.1074/jbc.M111.333385. more

  • Sharbati J, Lewin A, Kutz-Lohroff B, Kamal E, Einspanier R, Sharbati S (2011): Integrated MicroRNA-mRNA-Analysis of Human Monocyte Derived Macrophages upon Mycobacterium avium subsp. hominissuis Infection.
    PLoS ONE 6 (5): e20258. doi:10.1371/journal.pone.0020258. more

  • Tree JA, Patel J, Thom RE, Elmore MJ, Schäfer H, Williams A, Marsh PD (2010): Temporal changes in the gene signatures of BCG-vaccinated guinea pigs in response to different mycobacterial antigens.
    Vaccine 28 (50): 7979-7986. DOI: 10.1016/j.vaccine.2010.09.061. more

  • Sharbati S, Schramm K, Rempel S, Wang H, Andrich R, Tykiel V, Kunisch R, Lewin A (2009): Characterisation of porin genes from Mycobacterium fortuitum and their impact on growth.
    BMC Microbiology 9: 31. Epub 9 Feb 2009. more

  • Lewin A, Baus D, Kamal E, Bon F, Kunisch R, Maurischat S, Adonopoulou M, Eich K (2008): The mycobacterial DNA-binding protein 1 (MDP1) from Mycobacterium bovis BCG influences various growth characteristics.
    BMC Microbiol. 8 (1): 91. Epub 2008 Jun 10. more

  • Schäfer H, Klippert K, Meuer P, Borsdorf B, Kiderlen AF, Burger R (2007): Biologic activity of guinea pig IFN-γ in vitro.
    J. Interferon Cytokine Res. 27 (4): 305-316. more

  • Schäfer H, Kliem G, Kropp B, Burger R (2007): Monoclonal antibodies to guinea pig interferon-gamma: Tools for cytokine detection and neutralization.
    J. Immunol. Methods 328 (1-2): 106-117. Epub Sep 12. more

  • Sharbati-Tehrani S, Stephan J, Holland G, Appel B, Niederweis M, Lewin A (2005): Porins limit the intracellular persistence of Mycobacterium smegmatis.
    Microbiology 151: 2403-2410. more

  • Lewin A, Sharbati-Tehrani S (2005): [Slow growth rate of mycobacteria Possible reasons and significance for their pathogenicity]
    Bundesgesundheitsbl: Nov 8; [Epub ahead of print]. more

  • Sharbati-Tehrani S, Meister B, Appel B, Lewin A (2004): The porin MspA from Mycobacterium smegmatis improves growth of Mycobacterium bovis BCG.
    J. Int. Med. Microbiol. 294: 235-245. more

  • Lewin A, Freytag B, Meister B, Sharbati-Tehrani S, Schäfer H, Appel B (2003): Use of a quantitative TaqMan-PCR for the fast quantification of mycobacteria in broth culture, eukaryotic cell culture and tissue.
    J. Vet. Med. B 50: 505-509. more

  • Klünner T, Bartels T, Vordermeier M, Burger R, Schäfer H (2001): Immune reactions of CD4- and CD8-positive T cell subpopulations in spleen and lymph nodes of guinea pigs after vaccination with Bacillus Calmette Guérin.
    Vaccine 19 (15-16): 1968-1977. more