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

Citiulo F, Jacobsen ID, Miramón P, Schild L, Brunke S, Zipfel PF, Brock M, Hube B, Wilson D (2012) Candida albicans scavenges host zinc via Pra1 during endothelial invasion. PLOS Pathog 8(6), e1002777.
Mayer FL, Wilson D, Jacobsen ID, Miramón P, Große K, Hube B (2012) The novel Candida albicans transporter Dur31 Is a multi-stage pathogenicity factor. PLOS Pathog 8(3), e1002592.
Wilson D, Citiulo F, Hube B (2012) Zinc exploitation by pathogenic fungi. PLOS Pathog 8(12), e1003034. (Review)
Linde J, Wilson D, Hube B, Guthke R (2010) Regulatory network modelling of iron acquisition by a fungal pathogen in contact with epithelial cells. BMC Syst Biol 4, 148.
Almeida RS, Wilson D, Hube B (2009) Candida albicans iron acquisition within the host. FEMS Yeast Res 9(7), 1000-1012.
Almeida RS, Brunke S, Albrecht A, Thewes S, Laue M, Edwards JE, Filler SG, Hube B (2008) The hyphal-associated adhesin and invasin Als3 of Candida albicans mediates iron acquisition from host ferritin. PLOS Pathog 4(11), e1000217.