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Current and prospective therapeutic strategies: tackling Candida albicans and Streptococcus mutans cross-kingdom biofilm.

ABSTRACT: Candida albicans (C. albicans) is the most frequent strain associated with cross-kingdom infections in the oral cavity. Clinical evidence shows the co-existence of Streptococcus mutans (S. mutans) and C. albicans in the carious lesions especially in children with early childhood caries (ECC) and demonstrates the close interaction between them. During the interaction, both S. mutans and C. albicans have evolved a complex network of regulatory mechanisms to boost cariogenic virulence and modulate tolerance upon stress changes in the external environment. The intricate relationship and unpredictable consequences pose great therapeutic challenges in clinics, which indicate the demand for de novo emergence of potential antimicrobial therapy with multi-targets or combinatorial therapies. In this article, we present an overview of the clinical significance, and cooperative network of the cross-kingdom interaction between S. mutans and C. albicans. Furthermore, we also summarize the current strategies for targeting cross-kingdom biofilm.

SUBMITTER: Li Y

PROVIDER: S-EPMC10213903 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature

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Current and prospective therapeutic strategies: tackling Candida albicans and Streptococcus mutans cross-kingdom biofilm.

Li Yijun Y Huang Shan S Du Jingyun J Wu Minjing M Huang Xiaojing X

Frontiers in cellular and infection microbiology 20230511

Candida albicans (C. albicans) is the most frequent strain associated with cross-kingdom infections in the oral cavity. Clinical evidence shows the co-existence of Streptococcus mutans (S. mutans) and C. albicans in the carious lesions especially in children with early childhood caries (ECC) and demonstrates the close interaction between them. During the interaction, both S. mutans and C. albicans have evolved a complex network of regulatory mecha ...[more]

PMID: 37249973

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Project description:Streptococcus mutans and Candida albicans exhibit strong cariogenicity through cross-kingdom biofilm formation during the pathogenesis of dental caries. Caffeic acid phenethyl ester (CAPE), a natural compound, has potential antimicrobial effects on each species individually, but there are no reports of its effect on this dual-species biofilm. This study aimed to explore the effects of CAPE on cariogenic biofilm formation by S. mutans and C. albicans and the related mechanisms. The effect of CAPE on planktonic cell growth was investigated, and crystal violet staining, the anthrone-sulfuric acid assay and confocal laser scanning microscopy were used to evaluate biofilm formation. The structures of the formed biofilms were observed using scanning electron microscopy. To explain the antimicrobial effect of CAPE, quantitative real-time PCR (qRT-PCR) was applied to monitor the relative expression levels of cariogenic genes. Finally, the biocompatibility of CAPE in human oral keratinocytes (HOKs) was evaluated using the CCK-8 assay. The results showed that CAPE suppressed the growth, biofilm formation and extracellular polysaccharides (EPS) synthesis of C. albicans and S. mutans in the coculture system of the two species. The expression of the gtf gene was also suppressed by CAPE. The efficacy of CAPE was concentration dependent, and the compound exhibited acceptable biocompatibility. Our research lays the foundation for further study of the application of the natural compound CAPE as a potential antimicrobial agent to control dental caries-associated cross-kingdom biofilms. IMPORTANCE Severe dental caries is a multimicrobial infectious disease that is strongly induced by the cross-kingdom biofilm formed by S. mutans and C. albicans. This study aimed to investigate the potential of caffeic acid phenethyl ester (CAPE) as a natural product in the prevention of severe caries. This study clarified the inhibitory effect of CAPE on cariogenic biofilm formation and the control of cariogenic genes. It deepens our understanding of the synergistic cariogenic effect of S. mutans and C. albicans and provides a new perspective for the prevention and control of dental caries with CAPE. These findings may contribute to the development of CAPE as a promising antimicrobial agent targeting this caries-related cross-kingdom biofilm.

Project description:Candida albicans is frequently detected with heavy infection by Streptococcus mutans in plaque-biofilms from children with early-childhood caries (ECC). This cross-kingdom biofilm contains an extensive matrix of extracellular α-glucans that is produced by an exoenzyme (GtfB) secreted by S. mutans. Here, we report that mannans located on the outer surface of C. albicans cell-wall mediates GtfB binding, enhancing glucan-matrix production and modulating bacterial-fungal association within biofilms formed in vivo. Using single-molecule atomic force microscopy, we determined that GtfB binds with remarkable affinity to mannans and to the C. albicans surface, forming a highly stable and strong bond (1-2 nN). However, GtfB binding properties to C. albicans was compromised in strains defective in O-mannan (pmt4ΔΔ) or N-mannan outer chain (och1ΔΔ). In particular, the binding strength of GtfB on och1ΔΔ strain was severely disrupted (>3-fold reduction vs. parental strain). In turn, the GtfB amount on the fungal surface was significantly reduced, and the ability of C. albicans mutant strains to develop mixed-species biofilms with S. mutans was impaired. This phenotype was independent of hyphae or established fungal-biofilm regulators (EFG1, BCR1). Notably, the mechanical stability of the defective biofilms was weakened, resulting in near complete biomass removal by shear forces. In addition, these in vitro findings were confirmed in vivo using a rodent biofilm model. Specifically, we observed that C. albicans och1ΔΔ was unable to form cross-kingdom biofilms on the tooth surface of rats co-infected with S. mutans. Likewise, co-infection with S. mutans defective in GtfB was also incapable of forming mixed-species biofilms. Taken together, the data support a mechanism whereby S. mutans-secreted GtfB binds to the mannan layer of C. albicans to promote extracellular matrix formation and their co-existence within biofilms. Enhanced understanding of GtfB-Candida interactions may provide new perspectives for devising effective therapies to disrupt this cross-kingdom relationship associated with an important childhood oral disease.

Project description:Background: Cajuputs candy (CC), an Indonesian functional food, utilizes the bioactivity of Melaleuca cajuputi essential oil (MCEO) to maintain oral cavity health. Synergistic interaction between Candida albicans and Streptococcus mutans is a crucial step in the pathogenesis of early childhood caries. Our recent study revealed several alternative MCEOs as the main flavors in CC. The capacity of CC to interfere with the fungus-bacterium relationship remains unknown. This study aimed to evaluate CC efficacy to impair biofilm formation by these dual cariogenic microbes. Methods: The inhibition capacity of CC against mixed-biofilm comprising C. albicans and S. mutans was assessed by quantitative (crystal violet assay, tetrazolium salt [MTT] assay, colony forming unit/mL counting, biofilm-related gene expression) and qualitative analysis (light microscopy and scanning electron microscopy). Result: Both biofilm-biomass and viable cells were significantly reduced in the presence of CC. Scanning electron microscopy imaging confirmed this inhibition capacity, demonstrating morphology alteration of C. albicans, along with reduced microcolonies of S. mutans in the biofilm mass. This finding was related to the transcription level of selected biofilm-associated genes, expressed either by C. albicans or S. mutans. Based on qPCR results, CC could interfere with the transition of C. albicans yeast form to the hyphal form, while it suppressed insoluble glucan production by S. mutans. G2 derived from Mojokerto MCEO showed the greatest inhibition activity on the relationship between these cross-kingdom oral microorganisms (p < 0.05). Conclusion: In general, all CC formulas showed biofilm inhibition capacity. Candy derived from Mojokerto MCEO showed the greatest capacity to maintain the yeast form of C. albicans and to inhibit extracellular polysaccharide production by S. mutans. Therefore, the development of dual-species biofilms can be impaired effectively by the CC tested.

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Current and prospective therapeutic strategies: tackling Candida albicans and Streptococcus mutans cross-kingdom biofilm.

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Current and prospective therapeutic strategies: tackling <i>Candida albicans</i> and <i>Streptococcus mutans</i> cross-kingdom biofilm.

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