Nutrient acquisition in infections

In order to survive and replicate within the host, pathogens, such as pathogenic Candida species, need to obtain nutrients during infections. The host, on the other hand, attempts to withhold these nutrients from the pathogen as much as possible (“nutritional immunity”). A molecular tug-of-war starts, where both sides try to sequester essential micronutrients, for example iron or zinc, and get hold of carbon and nitrogen sources. The outcome of any infection is in large parts determined by this struggle, and understanding the mechanisms behind it will help finding novel ways to fight pathogens.

We are interested in the regulation of the fungal response to low micro- and macronutrient levels, which will be encountered by Candida cells in the host. Iron is an essential metal for almost all organisms and iron acquisition within a host is a prerequisite for any type of infection. For this reason, we are investigating the iron uptake systems, and their regulation, in both C. albicans and C. glabrata. Zinc, as a central cofactor in many proteins, is of similar importance, and our research focuses on the zinc acquisition systems Candida species have at their disposal. Finally, as an example of a macronutrient which fungi need to grow, we are investigating the nitrogen sources used by C. albicans during infections.

A fungal zincophore system. Invasive C. albicans hyphae secrete a zinc-binding protein, Pra1, which sequesters this essential metal from host cells before reassociating with the fungus via a cognate receptor, Zrt1.

Staff

Sascha Brunke
Osama Elshafee

Publications

Ramírez-Zavala B, Mottola A, Haubenreißer J, Schneider S, Allert S, Brunke S, Ohlsen K, Hube B, Morschhäuser J (2017) The Snf1-activating kinase Sak1 is a key regulator of metabolic adaptation and in vivo fitness of Candida albicans. Mol Microbiol 104(6), 989-1007.
Skrahina V, Brock M, Hube B, Brunke S (2017) Candida albicans Hap43 domains are required under iron starvation but not excess. Front Microbiol 8, 2388.
Gerwien F, Safyan A, Wisgott S, Hille F, Kämmer P, Linde J, Brunke S, Kasper L, Hube B (2016) A novel hybrid iron regulation network combines features from pathogenic and non-pathogenic yeasts. mBio 7(5), e01782-16.
Böttcher B, Palige K, Jacobsen ID, Hube B, Brunke S (2015) Csr1/Zap1 maintains zinc homeostasis and influences virulence in Candida dubliniensis but is not coupled to morphogenesis. Eukaryot Cell 14(7), 661-670.
Cavet JS, Perry RD, Brunke S, Darwin KH, Fierke CA, Imlay JA, Murphy M, Schryvers AB, Thiele DJ, Weiser JN (2015) Metal ions in host microbe interactions: The microbe perspective. In: Nriagu JO, Skaar EP (eds.) Trace Metals and Infectious Diseases. The MIT Press. Strüngmann Forum Reports. ISBN: 9780262029193.
Brunke S, Seider K, Richter ME, Bremer-Streck S, Ramachandra S, Kiehntopf M, Brock M, Hube B (2014) Histidine degradation via an aminotransferase increases the nutritional flexibility of Candida glabrata. Eukaryot Cell 13(6), 758-765.
Ene IV, Brunke S, Brown AJ, Hube B (2014) Metabolism in Fungal Pathogenesis. Cold Spring Harb Perspect Med 4(12),
Ramachandra S, Linde J, Brock M, Guthke R, Hube B, Brunke S (2014) Regulatory networks controlling nitrogen sensing and uptake in Candida albicans. PLOS One 9(3), e92734.
Seider K, Gerwien F, Kasper L, Allert S, Brunke S, Jablonowski N, Schwarzmüller T, Barz D, Rupp S, Kuchler K, Hube B (2014) Immune evasion, stress resistance, and efficient nutrient acquisition are crucial for intracellular survival of Candida glabrata within macrophages. Eukaryot Cell 13(1), 170-183.
Hennicke F, Grumbt M, Lermann U, Ueberschaar N, Palige K, Böttcher B, Jacobsen ID, Staib C, Morschhäuser J, Monod M, Hube B, Hertweck C, Staib P (2013) Factors supporting cysteine tolerance and sulfite production in Candida albicans. Eukaryot Cell 12(4), 604-613.