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Title Candida Albicans Stimulates Streptococcus Mutans Microcolony Development Via Cross-Kingdom Biofilm-Derived Metabolites
Clinical Question In children who have early childhood caries, would the implementation of an antifungal agent decrease the prevalence of Streptococcus Mutans in a biofilm?
Clinical Bottom Line It has been conveyed that Candida albicans stimulates Streptococcus mutans microcolony development via cross-kingdom biofilm-derived metabolites, but at low concentrations. The principal metabolite involved is farnesol.
Best Evidence (you may view more info by clicking on the PubMed ID link)
PubMed ID Author / Year Patient Group Study type
(level of evidence)
#1) 28134351Dongyeop/2017Bacterial and fungal biofilmsLaboratory study
Key resultsConditioned medium was gathered from single-species bacterial S. mutans, single-species fungal C. albicans, or a mix of bacterial-fungal biofilms spaced out at certain time-points: 6, 18 and 30  hours. These time periods correlate to active biofilm growth. “The results showed that BF-CM [bacterial and fungal conditioned media] collected at 18 h significantly promoted bacterial accumulation within biofilms compared to control (no supplementation, P < 0.001). In contrast, no significant increase in the bacterial cell population was detected when S. mutans was grown in CM preparations from single-species biofilms or from BF-CM at other time-points. It appears that during the initial phase of active biofilm formation (between 6 h to 18 h) the presence of cross-kingdom metabolites could be enhancing S. mutans cell growth, while at the later time point (30 h) this effect is attenuated possibly due to reduced microbial/metabolic activity. Thus, hereafter further experiments were focused on the bioactivity of BF-CM collected at 18 h on biofilm formation by S. mutans. Using different dilutions of BF-CM, the data showed a clear trend of increasing number of viable S. mutans-biofilm cells (>6-fold increase at highest BF-CM content vs. no supplementation) in a dose-dependent manner (r2 = 0.9) suggesting that BF-CM contains bacterial growth-inducing factors.” This experiment allows us to study the “chemical interactions between an opportunistic fungus and an oral pathogen, which in part help to explain the in vivo and clinical findings showing enhanced S. mutans carriage in the presence of C. albicans in plaque-biofilms associated with [early childhood caries].” One of the main modulators in this cross-kingdom biofilm is farnesol. At high concentrations, farnesol has been found to decrease the growth of both S. mutans and C. albicans. As a result, this can lessen the pathogenicity of the biofilm created by these two organisms. This shows that there is a possibility of utilizing an anti-fungal therapy approach in treating children with early childhood caries in the future.
#2) 24566629Falsetta/2014Six litters of 8 female Sprague Dawley rats aged 15 days. 4 groups: (1.) S. mutans infected, (2.) C. albicans infected, (3.) S. mutans plus C. albicans infected, and (4.) uninfected.Randomized Controlled Trial
Key resultsSix litters of 8 female Sprague Dawley rats were (1) S. mutans infected, (2) C. albicans infected, (3) S. mutans plus C. albicans infected, or (4) uninfected. The researchers evaluated the formation of a biofilm for each of the groups listed. “The jaws were aseptically dissected and were processed for microbiological analysis of each animal's plaque biofilms …”. They examined the EPS (extracellular matrix of polymeric substances)-mediated bacterium-fungus interaction when sucrose was present. It was found that the EPS-mediated matrix biofilm was denser and greater in size when both C. albicans and S. mutans were present, compared to just a single organism being present. The researchers measured different times in the group of rats that were infected with both organisms. It was found that by 8 hours of post infection, the first signs of C. albicans were detected. S. mutans was already present by 6 hours. After 42 hours, great amounts of fungal cells were present. “Furthermore, cospecies biofilms displayed more (at the early stage of 18 h) and larger (at 42 h) microcolonies than S. mutans-only biofilms (P, <0.05).” The significance of this study is that a biofilm becomes more virulent in time in animals. Since farnesol was used to reduce the pathogenicity of a cross-kingdom biofilm, this metabolite can potentially be used to reduce the pathogenicity in the jaws of Sprague Dawley rats. Most importantly, farnesol could possibly be used as an antifungal agent to decrease the prevalence of Streptococcus Mutans in a biofilm.
Evidence Search candida albicans AND streptococcus mutans
Comments on
The Evidence
Both experiments compared co-species infection/biofilm against C. albicans and S. mutans single-species infection/biofilms. These experiments should form the basis for further studies into the development of farnesol as a human therapeutic agent. I do see a promising result in clinical practice in the future. However since this has not yet been applied to human subjects, the cost of this therapy may place a burden on some patients.
Applicability The results of this experiment have not been utilized in human subjects yet. However, the main metabolite that was seen to decrease the growth of both C. albicans and S. mutans at high concentrations was farnesol. This metabolite could possibly be used to treat and prevent early childhood caries in the future. Since this therapy is not yet available, the cost of it could be a factor to some patients.
Specialty/Discipline (General Dentistry) (Basic Science)
Keywords Candida Albicans, Streptococcus Mutans, co-infection, biofilms, childhood, caries
ID# 3248
Date of submission: 05/09/2017spacer
E-mail Sernap3@livemail.uthscsa.edu
Author Peter Serna
Co-author(s) e-mail
Faculty mentor/Co-author Erica Oliveira, DDS, MPH
Faculty mentor/Co-author e-mail OLIVEIRAE@uthscsa.edu
Basic Science Rationale
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