Characterisation of Candida albicans, Actinomyces naeslundii and Streptococcus mutans interaction and its role in promoting oral carcinogenesis
AuthorArzmi, Mohd Hafiz
AffiliationMelbourne Dental School
Document TypePhD thesis
Access StatusThis item is embargoed and will be available on 2019-02-20. This item is currently available to University of Melbourne staff and students only, login required.
© 2016 Dr. Mohd Hafiz Arzmi
Candida albicans has been widely reported in the aetiology of oral cancer. However, the role of its interaction with members of the oral microbiome, such as Actinomyces naeslundii and Streptococcus mutans, in promoting oral carcinogenesis is still under investigation. The overall hypothesis of the present study is that polymicrobial biofilms of C. albicans, A. naeslundii and S. mutans are involved in oral carcinogenesis with the specific hypotheses as following: 1) Auto-aggregation and co-aggregation of C. albicans is strain-dependent; 2) Polymicrobial biofilm formation is C. albicans strain- and medium-dependent; 3) Polymicrobial interactions within biofilms grown in flow-cells affects C. albicans biofilm formation; and 4) Oral epithelial cells have an enhanced malignant phenotype when grown in the presence of polymicrobial biofilm effluent. The present study showed that C. albicans was able to auto-aggregate and co-aggregate with A. naeslundii and/or S. mutans during planktonic growth. Co-aggregation was shown to be variable between the eight strains of C. albicans with A. naeslundii and S. mutans found to co-aggregate on both yeast and hyphae of C. albicans. The static biofilm study showed that C. albicans formed yeast when grown in 25% artificial saliva medium (ASM) and hyphae when grown in RPMI-1640. Variability in biomass and metabolic activity was observed when C. albicans strains were grown as mono-cultured and polymicrobial biofilms. In addition, ASM-grown C. albicans, which predominantly forms yeast, was also able to form both mono-cultured and polymicrobial biofilms in a flow-cell environment. Overall the biomass of polymicrobial biofilms was found to be low relative to mono-cultured biofilms, indicating antagonistic interactions between species. The present study showed that biofilm effluent collected from flow-cell grown biofilms was able to promote oral carcinogenesis by increasing the adhesion of H357 cells (oral squamous cell carcinoma cell line) to extracellular matrix molecules. Furthermore, the expression of pro-inflammatory cytokines from H357 was found to increase when grown in conditioned media suggesting that the biofilm effluent might have a role in the promotion of oral carcinogenesis. In conclusion, polymicrobial interactions of C. albicans A. naeslundii and S. mutans promote oral carcinogenesis, thus supporting the hypothesis that polymicrobial biofilms of C. albicans, A. naeslundii and S. mutans are involved in oral cancer by promoting carcinogenesis. Moreover, this carcinogenesis promoting activity of polymicrobial biofilms is more likely to be C. albicans strain-specific.
Keywordsoral microbiology; immunology
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