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

Bissell AU, Rautschek J, Hoefgen S, Raguž L, Mattern DJ, Saeed N, Janevska S, Jojić K, Huang Y, Kufs JE, Herboeck B, Guo H, Hillmann F, Beemelmanns C, Valiante V (2022) Biosynthesis of the sphingolipid inhibitors sphingofungins in filamentous fungi requires aminomalonate as a metabolic precursor. ACS Chem Biol 17(2), 386-394.
Günther M*, Reimer C*, Herbst R*, Kufs JE, Rautschek J, Ueberschaar N, Zhang S, Peschel G, Reimer L, Regestein L, Valiante V, Hillmann F#, Stallforth P# (2022) Yellow polyketide pigment suppresses premature hatching in social amoeba. Proc Natl Acad Sci USA 119(43), e2116122119.
Kufs JE, Reimer C, Stallforth P, Hillmann F, Regestein L* (2022) The potential of amoeba-based processes for natural product syntheses. Curr Opin Biotechnol 77, 102766. (Review)
Kufs JE, Reimer C, Steyer E, Valiante V, Hillmann F, Regestein L (2022) Scale-up of an amoeba-based process for the production of the cannabinoid precursor olivetolic acid. Microb Cell Fact 21(1), 217.
Reimer C*, Kufs JE*, Rautschek J, Regestein L, Valiante V, Hillmann F (2022) Engineering the amoeba Dictyostelium discoideum for biosynthesis of a cannabinoid precursor and other polyketides. Nat Biotechnol 40(5), 751-758.
Richter I, Radosa S, Cseresnyés Z, Ferling I, Büttner H, Niehs SP, Gerst R, Figge MT, Hillmann F, Hertweck C (2022) Toxin-producing endosymbionts shield pathogenic fungus against micropredators. mBio 13(5), e0144022.
Boysen JM, Saeed N, Hillmann F (2021) Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus. Beilstein J Org Chem 17, 1814-1827. (Review)
Boysen JM, Saeed N, Wolf T, Panagiotou G, Hillmann F (2021) The peroxiredoxin asp f3 acts as redox sensor in Aspergillus fumigatus. Genes 12(5), 668.
Brantl V, Boysen JM, Yap A, Golubtsov E, Ruf D, Heinekamp T, Straßburger M, Dichtl K, Haas H, Hillmann F, Wagener J (2021) Peroxiredoxin Asp f3 is essential for Aspergillus fumigatus to overcome iron limitation during infection. mBio 12(4), e0097621.
Keizer EM, Valdes ID, Forn-Cuni G, Klijn E, Meijer AH, Hillman F, Wösten HAB, de Cock H (2021) Variation of virulence of five Aspergillus fumigatus isolates in four different infection models. PLOS One 16(7), e0252948.