Abstract: Objective: Streptococcus sanguis extract XLS is a bacteriostatic intracellular protein extracted from oral Streptococcus sanguis. To detect and analyze the metabolic changes of XLS on Candida albicans by non-targeted metabolomics, and to analyze its mechanism. Methods: The samples were prepared firstly. Experimental group: 0.5 mg/mL XLS was co-cultured with Candida albicans for 12 h; control group: pure Candida albicans was cultured for 12 h, with 6 biological replicates in each group. Two non-targeted metabolomics technologies were used to study the metabolic changes of samples. Multivariate analysis [(principal components analysis, PCA) and (partial least squares discriminant analysis, PLS-DA)] and univariate analysis (t test) were used to compare the differences. Results: PLS-DA and PCA analysis showed significant differences between two groups of samples. In this study, 160 positive ion differential metabolites were screened, of which 68 metabolites were up-regulated and 92 metabolites were down-regulated. Among the 90 negative ion differential metabolites, 52 metabolites were up-regulated and 38 metabolites were down-regulated. Through KEGG enrichment analysis, it was found that the pathways with significant pathway enrichment mainly included ascorbic acid and aldehyde acid metabolic pathways, amino acid synthesis, purine pyrimidine metabolic pathways, etc. In addition, some metabolites related to oxidative stress were also found, which were up-regulated in the experimental group compared with the control group. Conclusion: XLS has a significant effect on amino acid metabolism, lipid metabolism, purine and pyrimidine metabolism, and other processes of Candida albicans. XLS causes oxidative damage to Candida albicans cells by causing oxidative stress in Candida albicans, thereby inhibiting the growth and reproduction of Candida albicans.

Key words: XLS, Candida albicans, non-targeted metabolome, differential metabolites