Until 2022

Evolution of Microbial Interactions

A large number of infections in humans and animals is caused by microorganisms that are actually considered to be harmless soil dwellers. Often their pathogenicity arises not only from the formation of special virulence factors, but rather results from complex interactions of the pathogen with the immune system of the infected host. How such microorganisms could have acquired properties to colonize or persist in the host is poorly understood.

Fungi such as Aspergillus fumigatus but also some yeasts can be regarded as such environmentally acquired pathogens. Their typical habitats include compost heaps or leaf litter, where they feed on decaying plant material. Nevertheless, they can cause severe systemic diseases in immunocompromised patients upon infection. In addition, the host range is rather broad and includes amphibians, as well as birds. What are the evolutionary driving forces behind general mechanisms to invasively colonize the host or resist the innate immune response?

We are analyzing to which extent fungivorous amoebae as naturally occurring predators could have exerted a selective pressure on fungi, which encouraged the development of virulent traits, e.g. the camouflage the cell surface by pigments or increased resistance to reactive oxygen species. Both are likely to be useful in the defense against natural predators and during interactions with cells of the immune system.

The research group Miqwi is integrated into the structural unit Evolution of Microbial Interactions. The group deals with the application-oriented projects to identify, isolate and characterise novel natural products from the secondary metabolism of amoebae-microbe-interactions.

Head

Falk Hillmann
Head

Phagocytic escape

Fungi are using different strategies to avoid the deadly attacks and being eaten by innate immune cells. One way is to protect the surface of their spores by amorphous pigments and hydrophobic protein layers from recognition. We are particularly interested in whether these mechanisms are also targeted against amoebae and hence, are advantageous in natural environments. To approach these questions, we are exploiting the versatile model amoeba Dictyostelium and their lesser-known, but exclusively fungivorous relative, Protostelium mycophaga.

Oxidative stress defence

Reactive oxygen species (ROS) play an important role in almost all host-pathogen relationships. In the case of infection with Aspergillus fumigatus, this is particularly obvious: Patients with a genetic defect in superoxide formation (O2¯) are especially vulnerable to the often life-threatening invasive aspergillosis (IA). Phagocytes of the immune system are the major producers of O2¯. We are interested whether phagocyte derived ROS could pose a threat to fungi and if the ROS defense strategies may have been "trained" by microbial interactions.

Microbial interactions as source of new antiinfective compounds

The research group Miqwi is integrated into the structural unit Evolution of Microbial Interactions. The group deals with the application-oriented projects to identify, isolate and characterise novel natural products from the secondary metabolism of amoebae-microbe-interactions.

Visualization of microbial interactions and infection mechanisms (VITERAKT)

Using state-of-the art fluorescence microscopy, we investigate the production of natural products in microbial interactions. We screen binary interaction both at the macroscopic level using a stereo zoom microscope as well as at the microscopic level using a confocal laser-scanning microscope.

Publications

Novohradska S, Ferling I, Hillmann F (2017) Exploring virulence determinants of filamentous fungal pathogens through interactions with soil amoebae. Front Cell Infect Microbiol 7, 497. (Review)
Geib E, Gressler M, Viediernikova I, Hillmann F, Jacobsen ID, Nietzsche S, Hertweck C, Brock M (2016) A non-canonical melanin biosynthesis pathway protects Aspergillus terreus conidia from environmental stress. Cell Chem Biol 23(5), 587-597.
Hillmann F, Bagramyan K, Straßburger M, Heinekamp T, Hong TB, Bzymek KP, Williams JC, Brakhage AA, Kalkum M (2016) The crystal structure of peroxiredoxin Asp f3 provides mechanistic insight into oxidative stress resistance and virulence of Aspergillus fumigatus. Sci Rep 6, 33396.
Spaller T, Kling E, Glöckner G, Hillmann F, Winckler T (2016) Convergent evolution of tRNA gene targeting preferences in compact genomes. Mob DNA 7, 17.
Vaknin Y, Hillmann F, Iannitti R, Ben Baruch N, Sandovsky-Losica H, Shadkchan Y, Romani L, Brakhage A, Kniemeyer O, Osherov N (2016) Identification and characterization of a novel Aspergillus fumigatus rhomboid family putative protease RbdA involved in hypoxia sensing and virulence. Infect Immun 84(6), 1866-1878.
Hillmann F, Novohradská S, Mattern DJ, Forberger T, Heinekamp T, Westermann M, Winckler T, Brakhage AA (2015) Virulence determinants of the human pathogenic fungus Aspergillus fumigatus protect against soil amoeba predation. Environ Microbiol 17(8), 2858-2869.
Hillmann F, Shekhova E, Kniemeyer O (2015) Insights into the cellular responses to hypoxia in filamentous fungi. Curr Genet 61(3), 441-455.
Hillmann F, Linde J, Beckmann N, Cyrulies M, Strassburger M, Heinekamp T, Haas H, Guthke R, Kniemeyer O, Brakhage AA (2014) The novel globin protein fungoglobin is involved in low oxygen adaptation of Aspergillus fumigatus. Mol Microbiol 93(3), 539-553.
Kroll K, Pähtz V, Hillmann F, Vaknin Y, Schmidt-Heck W, Roth M, Jacobsen ID, Osherov N, Brakhage AA, Kniemeyer O (2014) Identification of hypoxia-inducible target genes of Aspergillus fumigatus by transcriptome analysis reveals cellular respiration as important contributor to hypoxic survival. Eukaryot Cell 13(9), 1241-1253.
Shopova I, Bruns S, Thywissen A, Kniemeyer O, Brakhage AA, Hillmann F (2013) Extrinsic extracellular DNA leads to biofilm formation and colocalizes with matrix polysaccharides in the human pathogenic fungus Aspergillus fumigatus. Front Microbiol 4, 141.