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

Among the diverse fungal opportunistic pathogens, 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 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 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 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 SC5314, which contributes to macrophage recognition and clearance.