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.

Publications

Van Ende M, Timmermans B, Vanreppelen G, Siscar-Lewin S, Fischer D, Wijnants S, Romero CL, Yazdani S, Rogiers O, Demuyser L, Van Zeebroeck G, Cen Y, Kuchler K, Brunke S, Van Dijck P (2021) The involvement of the Candida glabrata trehalase enzymes in stress resistance and gut colonization. Virulence 12(1), 329-345. Details PubMed Open Access PDF

Ho J, Wickramasinghe DN, Nikou SA, Hube B, Richardson JP, Naglik JR (2020) Candidalysin is a potent trigger of alarmin and antimicrobial peptide release in epithelial cells. Cells 9(3), 699. Details PubMed Open Access PDF

Ruben S, Garbe E, Mogavero S, Albrecht-Eckardt D, Hellwig D, Häder A, Krüger T, Gerth K, Jacobsen ID, Elshafee O, Brunke S, Hünniger K, Kniemeyer O, Brakhage AA, Morschhäuser J, Hube B, Vylkova S, Kurzai O, Martin R (2020) Ahr1 and Tup1 contribute to the transcriptional control of virulence-associated genes in Candida albicans. mBio 11(2), e00206-20. Details PubMed Open Access PDF

Westman J, Walpole GFW, Kasper L, Xue BY, Elshafee O, Hube B, Grinstein S (2020) Lysosome fusion maintains phagosome integrity during fungal infection. Cell Host Microbe 28(6), 798-812. Details PubMed Open Access PDF

Arastehfar A, Boekhout T, Butler G, De Cesare GB, Dolk E, Gabaldón T, Hafez A, Hube B, Hagen F, Hovhannisyan H, Iracane E, Kostrzewa M, Lackner M, Lass-Flörl C, Llorens C, Mixão V, Munro C, Oliveira-Pacheco J, Pekmezovic M, Pérez-Hansen A, Sanchez AR, Sauer FM, Sparbier K, Stavrou AA, Vaneechoutte M, Vatanshenassan M (2019) Recent trends in molecular diagnostics of yeast infections: from PCR to NGS. FEMS Microbiol Rev 43(5), 517-547. (Review) Details PubMed Open Access

Chu H, Duan Y, Lang S, Jiang L, Wang Y, Llorente C, Liu J, Mogavero S, Bosques-Padilla F, Abraldes JG, Vargas V, Tu XM, Yang L, Hou X, Hube B, Stärkel P, Schnabl B (2019) The Candida albicans exotoxin Candidalysin promotes alcohol-associated liver disease. J Hepatol 72(3), 391-400. Details PubMed

Correia I, Prieto D, Román E, Wilson D, Hube B, Alonso-Monge R, Pla J (2019) Cooperative role of MAPK pathways in the interaction of Candida albicans with the host Epithelium. Microorganisms 8(1), 48. Details PubMed Open Access PDF

Fischer D, Gessner G, Fill TP, Barnett R, Tron K, Dornblut K, Kloss F, Stallforth P, Hube B, Heinemann SH, Hertweck C, Scherlach K, Brunke S (2019) Disruption of membrane integrity by the bacteria-derived antifungal jagaricin. Antimicrob Agents Chemother 63(9), e00707-19. Details PubMed Open Access PDF

Ho J, Yang X, Nikou SA, Kichik N, Donkin A, Ponde NO, Richardson JP, Gratacap RL, Archambault LS, Zwirner CP, Murciano C, Henley-Smith R, Thavaraj S, Tynan CJ, Gaffen SL, Hube B, Wheeler RT, Moyes DL, Naglik JR (2019) Candidalysin activates innate epithelial immune responses via epidermal growth factor receptor. Nat Commun 10(1), 2297. Details PubMed Open Access PDF

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. Details PubMed

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. Details PubMed Open Access PDF

Naglik JR, Gaffen SL, Hube B (2019) Candidalysin: Discovery and function in Candida albicans infections. Curr Opin Microbiol 52, 100-109. (Review) Details PubMed Open Access PDF

Pekmezovic M, Mogavero S, Naglik JR, Hube B (2019) Host-pathogen interactions during female genital tract infections. Trends Microbiol 27(12), 982-996. (Review) Details PubMed

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. Details PubMed Open Access PDF

Gerwien F, Skrahina V, Kasper L, Hube B, Brunke S (2018) Metals in fungal virulence. FEMS Microbiol Rev 42(1), fux050. (Review) Details PubMed Open Access

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. Details PubMed Open Access

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) Details PubMed Open Access

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. Details PubMed Open Access

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. Details PubMed Open Access

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. Details PubMed

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. Details PubMed Open Access

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. Details PubMed Open Access

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. Details PubMed Open Access PDF

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. Details

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. Details PubMed

Ene IV, Brunke S, Brown AJ, Hube B (2014) Metabolism in Fungal Pathogenesis. Cold Spring Harb Perspect Med 4(12), Details PubMed

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. Details PubMed Open Access

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. Details PubMed

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. Details PubMed

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. Details PubMed Open Access

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. Details PubMed

Wilson D, Citiulo F, Hube B (2012) Zinc exploitation by pathogenic fungi. PLOS Pathog 8(12), e1003034. (Review) Details PubMed

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. Details PubMed

Almeida RS, Wilson D, Hube B (2009) Candida albicans iron acquisition within the host. FEMS Yeast Res 9(7), 1000-1012. Details PubMed

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. Details PubMed Open Access

Staff

Dr. Sascha Brunke

Phone: +49 3641 532-1222 Email: sascha.brunke@leibniz-hki.de

Osama Elshafee

Phone: +49 3641 532-1225 Email: osama.elshafee@leibniz-hki.de