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ORIGINAL RESEARCH article

Front. Cell. Infect. Microbiol.

Sec. Microbes and Innate Immunity

Volume 15 - 2025 | doi: 10.3389/fcimb.2025.1629373

Candida albicans and Staphylococcus aureus reciprocally promote their virulence factor secretion and pro-inflammatory effects

Provisionally accepted
Raymond PasmanRaymond Pasman1Bastiaan P KromBastiaan P Krom2Martijs J JonkerMartijs J Jonker1Wim C De LeeuwWim C De Leeuw1Gertjan KramerGertjan Kramer1Stanley BrulStanley Brul1Sebastian A J ZaatSebastian A J Zaat3Jianbo ZhangJianbo Zhang1*
  • 1Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, Netherlands
  • 2Academic Centre for Dentistry Amsterdam, University of Amsterdam, Amsterdam, Netherlands
  • 3Amsterdam Institute for Immunology and Infectious Diseases, Amsterdam UMC, Amsterdam, Netherlands

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Co-infections of Candida albicans and Staphylococcus aureus can significantly increase morbidity and mortality. However, the effect of C. albicans-S. aureus co-existence on virulence factors secretion and pro-inflammatory effects remain elusive. Here, we showed that co-culturing of C. albicans and S. aureus promoted the secretion of 7 cytolytic, 11 proteolytic, and 3 lipolytic extracellular virulence factors (ECVFs), owning to Als1/Als3-mediated interactions, the presence of C. albicans or its pH maintenance. Co-culturing promotes C. albicans hypha formation and β-glucan masking, suggesting that co-culturing enhances both C. albicans invasion and immune evasion. Moreover, the secretome of C. albicans-S. aureus co-culture increased pro-inflammatory pathways including promoting TNF-, NFKB-, and Toll-like receptor signalling pathways, as well as cytokine-cytokine receptor interactions in macrophages. Our findings support that C. albicans and S. aureus reciprocally promotes their virulence potential and proinflammatory effects, which may provide mechanistic insights into the increased morbidity and mortality during their coinfection in vivo.

Keywords: Candida albicans (C. albicans), Staphylococcus aureus, Inflammation, Virulence Factors, Macrophages

Received: 15 May 2025; Accepted: 24 Jul 2025.

Copyright: © 2025 Pasman, Krom, Jonker, De Leeuw, Kramer, Brul, Zaat and Zhang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Jianbo Zhang, Swammerdam Institute for Life Sciences, University of Amsterdam, Amsterdam, Netherlands

Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Supplementary Material