Symbiotic relationship between Streptococcus mutans and Candida albicans synergizes the virulence of plaque-biofilms in vivo
Falsetta, M.L., et al
Infection and Immunity. 2014. Published ahead of print 24 February 2014, doi: 10.1128/IAI.00087-14.
Streptococcus mutans is often cited as the main bacterial pathogen in dental caries, particularly in early-childhood caries (ECC). S. mutans may not act alone; Candida albicans cells are frequently detected along with heavy infection by S. mutans in plaque-biofilms from ECC-affected children. It remains to be elucidated whether this association is involved in the enhancement of biofilm virulence. We showed that the ability of these organisms together to form biofilms is enhanced in vitro and in vivo. The presence of C. albicans augments exopolysaccharides (EPS) production, such that co-species biofilms accrue more biomass and harbor more viable S. mutans cells than single-species biofilms. The resulting three-dimensional biofilm architecture displays sizeable S. mutans-microcolonies surrounded by fungal cells, which are enmeshed in a dense EPS-rich matrix. Using a rodent model, we explored the implications of this cross-kingdom interaction in the pathogenesis of dental caries. Co-infected animals displayed increased levels of infection and elevated microbial-carriage within plaque-biofilms compared to those infected with either alone. Furthermore, co-infection synergistically enhanced biofilm virulence, leading to an aggressive onset of the disease with rampant carious lesions. Our in vitro data also revealed that glucosyltransferase-derived EPS is a key mediator of co-species biofilm development, and that co-existence with C. albicans induces the expression of virulence genes in S.mutans (e.g. gtfB,fabM). We also found that Candida-derived β1,3-glucans contribute to EPS-matrix structure, while fungal mannan and β-glucan provide sites for GtfB binding-activity. Altogether, we demonstrate a novel mutualistic bacterial-fungal relationship that occurs at a clinically relevant site to amplify the severity of a ubiquitous infectious disease.
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