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.
(2019) The Itaconate Pathway Is a Central Regulatory Node Linking Innate Immune Tolerance and Trained Immunity. Cell Metab [Accepted]
(2019) CARD9+ microglia promote antifungal immunity via IL-1β- and CXCL1-mediated neutrophil recruitment. Nat Immunol 20(5), 559-570.
(2019) Disruption of membrane integrity by the bacteria-derived antifungal jagaricin. Antimicrob Agents Chemother [Accepted]
(2019) Recent trends in molecular diagnostics of yeast infections: from PCR to NGS. FEMS Microbiol Rev ,
(2019) Frontline Science: Endotoxin-induced immunotolerance is associated with loss of monocyte metabolic plasticity and reduction of oxidative burst. J Leukoc Biol [Accepted]
(2019) Candidalysin activates innate epithelial immune responses via epidermal growth factor receptor. Nat Commun 10(1), 2297.
(2019) A systems genomics approach identifies SIGLEC15 as a susceptibility factor in recurrent vulvovaginal candidiasis. Sci Transl Med [Accepted]
(2019) Candidalysin is required for neutrophil recruitment and virulence during systemic Candida albicans infection Journal of Infectious Diseases [Accepted]
(2018) Metals in fungal virulence. FEMS Microbiol Rev 42(1), (Review)
(2017) The fungal pathogen Candida glabrata does not depend on surface ferric reductases for iron acquisition. Front Microbiol 8, 1055.
(2017) Zinc limitation induces a hyper-adherent goliath phenotype in Candida albicans. Front Microbiol 8, 2238.
(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.
(2017) Candida albicans Hap43 domains are required under iron starvation but not excess. Front Microbiol 8, 2388.
(2017) Metabolic adaptation of intracellular bacteria and fungi to macrophages. Int J Med Microbiol , pii: S1438-4221(17)30322-3. (Review)
(2016) A novel hybrid iron regulation network combines features from pathogenic and non-pathogenic yeasts. mBio 7(5), e01782-16.
(2015) Csr1/Zap1 maintains zinc homeostasis and influences virulence in Candida dubliniensis but is not coupled to morphogenesis. Eukaryot Cell 14(7), 661-670.
(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.
(2014) Histidine degradation via an aminotransferase increases the nutritional flexibility of Candida glabrata. Eukaryot Cell 13(6), 758-765.
(2014) Metabolism in Fungal Pathogenesis. Cold Spring Harb Perspect Med 4(12),
(2014) Regulatory networks controlling nitrogen sensing and uptake in Candida albicans. PLOS One 9(3), e92734.
(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.
(2013) Factors supporting cysteine tolerance and sulfite production in Candida albicans. Eukaryot Cell 12(4), 604-613.
(2012) Candida albicans scavenges host zinc via Pra1 during endothelial invasion. PLOS Pathog 8(6), e1002777.
(2012) The novel Candida albicans transporter Dur31 Is a multi-stage pathogenicity factor. PLOS Pathog 8(3), e1002592.
(2012) Zinc exploitation by pathogenic fungi. PLOS Pathog 8(12), e1003034. (Review)
(2010) Regulatory network modelling of iron acquisition by a fungal pathogen in contact with epithelial cells. BMC Syst Biol 4, 148.
(2009) Candida albicans iron acquisition within the host. FEMS Yeast Res 9(7), 1000-1012.
(2008) The hyphal-associated adhesin and invasin Als3 of Candida albicans mediates iron acquisition from host ferritin. PLOS Pathog 4(11), e1000217.