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Albumin Neutralizes Hydrophobic Toxins and Modulates Candida albicans Pathogenicity

Research output: Contribution to journalArticlepeer-review

Sophie Austermeier, Marina Pekmezovic, Pauline Porschitz, Sejeong Lee, Nessim Kichik Rodriguez, Dave Moyes, Jemima Ho, Natalia Kotowicz, Julian Naglik, Bernhard Hube, Mark S. Gresnigt

Original languageEnglish
Article numbere00531-21
Pages (from-to)e0053121
JournalMbio
Volume12
Issue number3
Early online date22 Jun 2021
DOIs
Accepted/In press22 May 2021
E-pub ahead of print22 Jun 2021
Published29 Jun 2021

Bibliographical note

Funding Information: innovation program under grant agreement 847507 (HDM-FUN). B.H. is further supported by the DFG within the Balance of the Microverse Cluster (Germanýs Excellence Strategy EXC 2051, Project-ID 390713860). J.R.N. was supported by grants from the Wellcome Trust (214229_Z_18_Z), the National Institutes of Health (NIH; R37-DE022550), and the NIH Research at Guys and St. Thomas’s NHS Foundation Trust and the King’s College London Biomedical Research Centre (IS-BRC-1215-20006). Funding Information: M.S.G. was supported by the German Research Foundation (Deutsche Forsch-ungsgemeinschaft [DFG]) Emmy Noether Program (project 434385622/GR 5617/1-1), an Alexander von Humboldt postdoctoral fellowship, and Research Grant 2019 from the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). S.A. and B.H. were supported by funding from the European Union’s Horizon 2020 research and Funding Information: M.S.G. was supported by the German Research Foundation (Deutsche Forsch-ungsgemeinschaft [DFG]) Emmy Noether Program (project 434385622/GR 5617/1-1), an Alexander von Humboldt postdoctoral fellowship, and Research Grant 2019 from the European Society of Clinical Microbiology and Infectious Diseases (ESCMID). S.A. and B.H. were supported by funding from the European Union?s Horizon 2020 research and innovation program under grant agreement 847507 (HDM-FUN). B.H. is further supported by the DFG within the Balance of the Microverse Cluster (German?s Excellence Strategy EXC 2051, Project-ID 390713860). J.R.N. was supported by grants from the Wellcome Trust (214229_Z_18_Z), the National Institutes of Health (NIH; R37-DE022550), and the NIH Research at Guys and St. Thomas?s NHS Foundation Trust and the King?s College London Biomedical Research Centre (IS-BRC-1215-20006). We thank Cor Jacobs from the department of Experimental Internal Medicine, Radboud University Medical Center, for kindly providing some of the albumin preparations. Publisher Copyright: © 2021 Austermeier et al.

King's Authors

Abstract

Albumin is abundant in serum but is also excreted at mucosal surfaces and enters tissues when inflammation increases vascular permeability. Host-associated opportunistic pathogens encounter albumin during commensalism and when causing infections. Considering the ubiquitous presence of albumin, we investigated its role in the pathogenesis of infections with the model human fungal pathogen, Candida albicans. Albumin was introduced in various in vitro models that mimic different stages of systemic or mucosal candidiasis, where it reduced the ability of C. albicans to damage host cells. The amphipathic toxin candidalysin mediates necrotic host cell damage induced by C. albicans. Using cellular and biophysical assays, we determined that albumin functions by neutralizing candidalysin through hydrophobic interactions. We discovered that albumin, similarly, can neutralize a variety of fungal (α-amanitin), bacterial (streptolysin O and staurosporin), and insect (melittin) hydrophobic toxins. These data suggest albumin as a defense mechanism against toxins, which can play a role in the pathogenesis of microbial infections. IMPORTANCE Albumin is the most abundant serum protein in humans. During inflammation, serum albumin levels decrease drastically, and low albumin levels are associated with poor patient outcome. Thus, albumin may have specific functions during infection. Here, we describe the ability of albumin to neutralize hydrophobic microbial toxins. We show that albumin can protect against damage induced by the pathogenic yeast C. albicans by neutralizing its cytolytic toxin candidalysin. These findings suggest that albumin is a toxin-neutralizing protein that may play a role during infections with toxin-producing microorganisms.

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