The 'microbial universe'
There are approximately 1,000.000.000.000.000.000.000. 000.000.000 (that's a 1 followed by 30 zeros) individual bacteria and archaea on earth, and around 1,000.000. 000.000.00 (a 1 followed by 14 zeros) bacteria inhabit a single human being at any time. These inconceivably enormous numbers quite nicely demonstrate that besides the enormity of the universe with its myriads of galaxies and stars, there is a second, yet invisible 'universe' surrounding and inhabiting us. This 'microbial universe' consists of microbes including archaea, bacteria, fungi, viruses, algae and protozoa. Microbes have been on earth far longer than us humans and influence about everything on our planet. Indeed, it can be speculated with relative certainty that microbes will still be around on earth long, long time after the last human has vanished from this planet. The vast majority of microbes are harmless to us humans. Indeed, many microbes are beneficial to us and directly help us staying healthy. Compared to the enormity of total microbial cells on earth, there is, however, a very small number of microbes that are very well adapted to cause disease in humans. These microbes include fungal pathogens. Because fungi cause life-threatening infections in humans, are difficult to treat because of the similarities they share with human cells, and because they are largely understudied compared to other microbes, my research passion was to identify novel approaches of treating and preventing fungal infections.
Top: B. safensis cells; Middle: C. albicans yeast cells; Bottom: C. albicans hyphae
Photo Credit: F. Mayer
Fungal pathogens as a major threat to human health
Fungal pathogens are largely ignored as the cause of life-threatening infections in humans compared to bacterial and viral pathogens. However, unbeknownst to most people, they cause at least as many deaths per year as malaria or tuberculosis. Major fungal pathogens include Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus. These three fungi alone kill at least 2,000.000 people each year.
C. albicans colonies on hypha-inducing medium
Photo Credit: F. Mayer
Top: C. albicans hyphae fluorescently stained with calcofluor white (blue) and Concanavalin A (red); Bottom: C. albicans microcolony on macrophages
Photo Credit: F. Mayer
My previous research projects
  • Fungal-bacterial interspecies interactions
  • Antifungal drug discovery
  • Capsule formation as a  fungal virulence factor
Fungal-bacterial interspecies interactions
In this project, I studied the interaction of environmental bacteria with the fungal pathogens Cryptococcus neoformans, and Candida albicans. Specifically, I was interested in identifying bacteria that exerted antifungal activities. I have discovered that the soil bacterium Bacillus safensis potently blocks biofilm formation and virulence factor production by both C. neoformans and C. albicans, in part via targeting fungal cell wall chitin.
Bacterial cells (B. safensis) attaching to a fungal hypha (C. albicans)
Photo Credit: F. Mayer
Antifungal drug discovery
There are currently only few antifungal drugs available to treat patients suffering from fungal infections. Moreover, many fungal pathogens develop drug resistance over time. Only one new class of antifungal drugs has been developed in the past 30 years. This is in part due to the major challenge of identifying fungal-specific drug targets. In this project, I performed screenings of novel compound collections (e.g., the 'Pathogen Box' distributed by Medicines for Malaria Venture, Switzerland). My screen of 400 compounds from the Pathogen Box led to the identification of one specific compound with potent activity against C. albicans and C. neoformans in nutrient-limited media. Further analyses revealed that this compound likely exerts its antifungal activity at the level of the cell wall, a structure that is not found in human cells.
Heat map of fungal growth in presence of antimicrobial compounds; OD600, optical density at 600 nm
Photo Credit: F. Mayer
Capsule formation as a fungal virulence factor
The major virulence factor of C. neoformans is the polysaccharide capsule which surrounds the cell body and protects the fungus from attack by cells of the human immune system. Fungal mutants with defective capsule biosynthesis are usually strongly reduced in virulence. In this project, I aimed to identify previously uncharacterized fungal genes that encode proteins required for normal capsule formation. Gaining a more detailed understanding of capsule formation by C. neoformans may lead to the development of new antifungal drugs.
C. neoformans cells stained with India ink to visualize the capsule (light gray halo around cells)
Photo Credit: F. Mayer