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.
(2019) CARD9+ microglia promote antifungal immunity via IL-1β- and CXCL1-mediated neutrophil recruitment. Nat Immunol 20(5), 559-570. Details PubMed
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(2017) The fungal pathogen Candida glabrata does not depend on surface ferric reductases for iron acquisition. Front Microbiol 8, 1055. Details PubMed Open Access
(2017) Zinc limitation induces a hyper-adherent goliath phenotype in Candida albicans. Front Microbiol 8, 2238. Details PubMed Open Access
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(2015) Csr1/Zap1 maintains zinc homeostasis and influences virulence in Candida dubliniensis but is not coupled to morphogenesis. Eukaryot Cell 14(7), 661-670. Details PubMed Open Access PDF
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(2014) Histidine degradation via an aminotransferase increases the nutritional flexibility of Candida glabrata. Eukaryot Cell 13(6), 758-765. Details PubMed
(2014) Metabolism in Fungal Pathogenesis. Cold Spring Harb Perspect Med 4(12), Details PubMed
(2014) Regulatory networks controlling nitrogen sensing and uptake in Candida albicans. PLOS One 9(3), e92734. Details PubMed Open Access
(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. Details PubMed
(2013) Factors supporting cysteine tolerance and sulfite production in Candida albicans. Eukaryot Cell 12(4), 604-613. Details PubMed
(2012) Candida albicans scavenges host zinc via Pra1 during endothelial invasion. PLOS Pathog 8(6), e1002777. Details PubMed Open Access
(2012) The novel Candida albicans transporter Dur31 Is a multi-stage pathogenicity factor. PLOS Pathog 8(3), e1002592. Details PubMed
(2012) Zinc exploitation by pathogenic fungi. PLOS Pathog 8(12), e1003034. (Review) Details PubMed
(2010) Regulatory network modelling of iron acquisition by a fungal pathogen in contact with epithelial cells. BMC Syst Biol 4, 148. Details PubMed
(2009) Candida albicans iron acquisition within the host. FEMS Yeast Res 9(7), 1000-1012. Details PubMed
(2008) The hyphal-associated adhesin and invasin Als3 of Candida albicans mediates iron acquisition from host ferritin. PLOS Pathog 4(11), e1000217. Details PubMed Open Access
