Baicalin promotes β-1,3-glucan exposure in Candida albicans and enhances macrophage response

Front Cell Infect Microbiol. 2024 Dec 9:14:1487173. doi: 10.3389/fcimb.2024.1487173. eCollection 2024.

Abstract

Among the diverse fungal opportunistic pathogens, Candida albicans garners significant attention due to its wide range of infections and high frequency of occurrence. The emergence of resistance and the limited number of antifungals drives the need to develop novel antifungal drugs. Although the natural product baicalin has been shown to trigger apoptosis in C. albicans in previous experiments, its influence on cell wall (CW) structure along with immune recognition remains elusive. In this work, baicalin showed a significant killing effect against C. albicans SC5314. Moreover, CW destruction, characterized by β-1,3-glucan unmasking and chitin deposition, was observed as a consequence of the treatment with baicalin. The RNA sequencing analysis revealed that treatment with baicalin resulted in eight hundred forty-two differentially expressed genes (DEGs). Sixty-five genes, such as GSC1, ENG1, CHS3, GWT1, and MKC1, were associated with CW organization or biogenesis. Baicalin-pretreated C. albicans SC5314 was phagocytosed more efficiently by RAW264.7 macrophages, accompanied by increased TNF-α and IL-1β production. Accordingly, it is hypothesized that baicalin could stimulate β-1,3-glucan unmasking by governing CW-associated gene expression in C. albicans SC5314, which contributes to macrophage recognition and clearance.

Keywords: Candida albicans; baicalin; macrophage; transcriptome; β-1,3-glucan.

MeSH terms

  • Animals
  • Antifungal Agents* / pharmacology
  • Candida albicans* / drug effects
  • Cell Wall* / drug effects
  • Cell Wall* / metabolism
  • Chitin / pharmacology
  • Flavonoids* / pharmacology
  • Gene Expression Profiling
  • Gene Expression Regulation, Fungal / drug effects
  • Interleukin-1beta / metabolism
  • Macrophages* / drug effects
  • Macrophages* / immunology
  • Macrophages* / metabolism
  • Macrophages* / microbiology
  • Mice
  • Phagocytosis / drug effects
  • RAW 264.7 Cells / drug effects
  • Tumor Necrosis Factor-alpha / metabolism
  • beta-Glucans* / metabolism
  • beta-Glucans* / pharmacology

Substances

  • baicalin
  • Flavonoids
  • beta-Glucans
  • Antifungal Agents
  • beta-1,3-glucan
  • Chitin
  • Tumor Necrosis Factor-alpha
  • Interleukin-1beta

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was funded by the National Natural Science Foundation of China (82374115), the Anhui Provincial Natural Science Foundation (2108085MH315), the Natural Science Foundation of Anhui Institution of Higher Education (2022AH050522 and 2024AH051043), the High-level Talents Support Plan of Anhui University of Chinese Medicine (2022rcyb006).