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Unit 19: Sexually Transmitted Bacterial Pathogens

Head:
Dagmar Heuer
deputy:
Sebastian Banhart

Staff

Dr. Lukas Aeberhard
Dr. Sebastian Banhart
Dipl. Biochem. Sophia Koch
Laura Rose, M.Sc.
Dipl. Biotech. Andrea Martini

Subject

Chlamydiae are obligate intracellular bacterial pathogens. With more than 90 million new infections per year worldwide, they are amongst the most frequent sexually transmitted bacteria. In women C. trachomatis infections can cause serious complications which can lead to infertility or ectopic pregnancies. In addition, there are infections with zoonotic Chlamydiae (ornithoses), which can cause severe disease such as pneumonia. Apart from their significance as pathogens, Chlamydiae have an intimate relationship with their host and are able to reprogram the infected cell, which makes them an attractive model organisms to investigate such changes.

The goal of our work is the de-coding of specific pathogen host interactions which permit a deeper understanding of the molecular mechanisms of infections and virulence as well as of fundamental cellular processes such as lipid transport. Our work focuses on the sophisticated mechanisms which allow intracellular bacteria to set up their niche within the host cell and maintain it in order to have access to nutrients which are vital for them, such as sphingolipids or iron. Based on our findings, we aim to derive new anti-microbial strategies.

A review article on the topic can be found here.

Projects

It is interesting to note that not only for Chlamydiae infections but also for infections with other human pathogens such as Salmonella spp or Toxoplasma gondii a structural change and recruitment of the Golgi apparatus (GA) to the bacterial/parasitic inclusions (see photo) can be observed. In how far this influences the pathogen propagation and supply with nutrients such as sphingolipids is hardly understood so far.

In future works we want to understand how Chlamydiae fragment and recruit the Golgi apparatus, how they take up lipids, mainly sphingolipids and whether this is an adaptation to the human host. In our work we focus on the following three core areas:

  1. The mechanism of Golgi fragmentation and its relevance for sphingolipid transport to Chlamydiae,
  2. the bacterial and cellular factors which are involved in the development and maintenance of the chlamydial inclusion,
  3. the molecular basis of the host cell specificity of human and zoonotic Chlamydiae within the framework of the collaborative research project “Zoonotic Chlamydiae”.

Third-party funded projects

Date: 01.04.2017

Publications

  • Koch-Edelmann S, Banhart S, Saied EM, Rose L, Aeberhard L, Laue M, Doellinger J, Arenz C, Heuer D (2017): The cellular ceramide transport protein CERT promotes Chlamydia psittaci infection and controls bacterial sphingolipid uptake.
    Cell. Microbiol.: Epub May 19. doi: 10.1111/cmi.12752. more

  • Aeberhard L, Banhart S, Fischer M, Jehmlich N, Rose L, Koch S, Laue M, Renard BY, Schmidt F, Heuer D (2015): The proteome of the isolated Chlamydia trachomatis containing vacuole reveals a complex trafficking platform enriched for retromer components.
    PLoS Pathog. 11 (6): e1004883. Epub Jun 4. doi: 10.1371/journal.ppat.1004883. more

  • Saied EM, Banhart S, Bürkle SE, Heuer D, Arenz C (2015): A series of ceramide analogs modified at the 1-position with potent activity against the intracellular growth of Chlamydia trachomatis.
    Future Med. Chem. 7 (15): 1971–1980. Epub Oct 23. doi: 10.4155/fmc.15.126. more

  • Madela K, Banhart S, Zimmermann A, Piesker J, Bannert N, Laue M (2014): A simple procedure to analyze positions of interest in infectious cell cultures by correlative light and electron microscopy.
    Methods Cell Biol. 124: 93–110. Epub Oct 3. doi: 10.1016/B978-0-12-801075-4.00005-7. more

  • Knittler MR, Berndt A, Böcker S, Dutow P, Hänel F, Heuer D, Kägebein D, Klos A, Koch S et al. (2014): Chlamydia psittaci: New insights into genomic diversity, clinical pathology, host–pathogen interaction and anti-bacterial immunity.
    Int. J. Med. Microbiol. 304 (7): 877–893. Epub Jun 28. doi: 10.1016/j.ijmm.2014.06.010. more

  • Häcker G, Ojcius DM, Heuer D (2014): Is the hoopla about CPAF justified?.
    Pathog. Dis. 72: 1-2. Epub Aug 11. doi: 10.1111/2049-632X.12211. more

  • Grützke J, Rindte K, Goosmann C, Silvie O, Rauch C, Heuer D et al. (2014): The spatiotemporal dynamics and membranous features of the Plasmodium liver stage tubovesicular network.
    Traffic 15 (4): 362-382. Epub Jan 15. doi: 10.1111/tra.12151. more

  • Banhart S, Saied EM, Martini A, Koch S, Aeberhard L, Madela K, Arenz C, Heuer D (2014): Improved plaque assay identifies a novel anti-Chlamydia ceramide derivative with altered intracellular localization.
    Antimicrob. Agents Chemother. 58 (9): 5537-5546. Epub Jul 7. doi: 10.1128/AAC.03457-14. more

  • Heymann J, Lipinski AR, Bauer B, Meyer TF, Heuer D (2013): Chlamydia trachomatis infection prevents front-rear polarity of migrating HeLa cells.
    Cell. Microbiol. 15 (7): 1059-1069. Epub Jan 28. doi: 10.1111/cmi.12114. more

  • Bhabak KP, Hauser A, Redmer S, Banhart S, Heuer D, Arenz C (2013): Development of a novel FRET probe for the real-time determination of ceramidase activity.
    Chembiochem. 14 (9): 1049-1052. doi: 10.1002/cbic.201300207. Epub May 31. more

  • Christian JG, Heymann J, Paschen SA, Vier J, Schauenburg L, Rupp J, Meyer TF, Häcker G, Heuer D (2011): Targeting of a chlamydial protease impedes intracellular bacterial growth.
    PLoS Pathog. 7 (9): e1002283. Epub Sep 29. more

  • Mehlitz A, Banhart S, Mäurer AP, Kaushansky A, Gordus AG, Zielecki J, Macbeath G, Meyer TF (2010): Tarp regulates early Chlamydia-induced host cell survival through interactions with the human adaptor protein SHC1.
    J. Cell Biol. 190 (1): 143–157. doi: 10.1083/jcb.200909095. more

  • Karlas A, Machuy N, Shin Y, Pleissner KP, Artarini A, Heuer D, Becker D, Khalil H, Ogilvie LA, Hess S, Mäurer AP, Müller E, Wolff T, Rudel T, Meyer TF (2010): Genome-wide RNAi screen identifies human host factors crucial for influenza virus replication.
    Nature 463 (7282): 818-822. Epub Jan 17. more

  • Rejman Lipinski A, Heymann J, Meissner C, Karlas A, Brinkmann V, Meyer TF, Heuer D (2009): Rab6 and Rab11 regulate Chlamydia trachomatis development and golgin-84-dependent Golgi fragmentation.
    PLoS Pathog. 5 (10): e1000615. doi:10.1371/journal.ppat.1000615. more

  • Heuer D , Rejman Lipinski A, Machuy N, Karlas A, Wehrens A, Siedler F, Brinkmann V, Meyer TF (2009): Chlamydia causes fragmentation of the Golgi compartment to ensure reproduction.
    Nature 457: 731-735.

  • Mehlitz A, Banhart S, Hess S, Selbach M, Meyer TF (2008): Complex kinase requirements for Chlamydia trachomatis Tarp phosphorylation.
    FEMS Microbiol. Lett. 289: 233-240.

  • Heuer D, Kneip C, Maurer AP, Meyer TF (2007): Tackling the intractable - approaching the genetics of Chlamydiales.
    Int. J. Med. Microbiol. 297: 569-576.

  • Kirchner M, Heuer D, Meyer TF (2005): CD46-independent binding of neisserial type IV pili and the major pilus adhesin, PilC, to human epithelial cells.
    Infect. Immun. 73: 3072-3082.

  • Heuer D, Brinkmann V, Meyer TF, Szczepek AJ (2003): Expression and translocation of chlamydial protease during acute and persistent infection of the epithelial HEp-2 cells with Chlamydophila (Chlamydia) pneumoniae.
    Cell. Microbiol. 5: 315-322.

  • Wagner R, Heuer D, Wolff T, Herwig A, Klenk HD (2002): N-Glycans attached to the stem domain of haemagglutinin efficiently regulate influenza A virus replication.
    J. Gen. Virol 83: 601-609 published online 27. November 2001. more

  • Klenk HD, Wagner R, Heuer D, Wolff T (2002): Importance of hemagglutinin glycosylation for the biological functions of influenza virus.
    Virus Res. 82: 73-75.