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

Ikonomova SP, Moghaddam-Taaheri P, Wang Y, Doolin MT, Stroka KM, Hube B, Karlsson AJ (2019) Effects of histatin 5 modifications on antifungal activity and kinetics of proteolysis. Protein Sci 29(2), 480-493.
Ishchuk OP, Ahmad KM, Koruza K, Bojanovič K, Sprenger M, Kasper L, Brunke S, Hube B, Säll T, Hellmark T, Gullstrand B, Brion C, Freel K, Schacherer J, Regenberg B, Knecht W, Piškur J (2019) RNAi as a tool to study virulence in the pathogenic yeast Candida glabrata. Front Microbiol 10, 1679.
Naglik JR, Gaffen SL, Hube B (2019) Candidalysin: Discovery and function in Candida albicans infections. Curr Opin Microbiol 52, 100-109. (Review)
Pekmezovic M, Mogavero S, Naglik JR, Hube B (2019) Host-pathogen interactions during female genital tract infections. Trends Microbiol 27(12), 982-996. (Review)
Swidergall M, Khalaji M, Solis N, Moyes D, Drummond R, Hube B, Lionakis M, Murdoch C, Filler S, Naglik J (2019) Candidalysin is required for neutrophil recruitment and virulence during systemic Candida albicans infection. J Infect Dis 220(9), 1477-1488.
Gerwien F, Skrahina V, Kasper L, Hube B, Brunke S (2018) Metals in fungal virulence. FEMS Microbiol Rev 42(1), fux050. (Review)
Guerrero QW, Fan L, Brunke S, Milkowski A, Rosado-Mendez IM, Hall TJ (2018) Power spectrum consistency among systems and transducers. Ultrasound Med Biol 44(11), 2358-2370.
Sprenger M, Kasper L, Hensel M, Hube B (2018) Metabolic adaptation of intracellular bacteria and fungi to macrophages. Int J Med Microbiol 308(1), 215-227. (Review)
Gerwien F, Safyan A, Wisgott S, Brunke S, Kasper L, Hube B (2017) The fungal pathogen Candida glabrata does not depend on surface ferric reductases for iron acquisition. Front Microbiol 8, 1055.
Malavia D, Lehtovirta-Morley LE, Alamir O, Weiß E, Gow NAR, Hube B, Wilson D (2017) Zinc limitation induces a hyper-adherent goliath phenotype in Candida albicans. Front Microbiol 8, 2238.