Date of Award
Master of Dental Science (MDS)
Jegdish P. Babu, Ph.D.
Kenneth M. Anderson, D.D.S., M.S. David R. Cagna, D.M.D., M.S. Audrey M. Selecman, D.D.S., M.S. Edwin L. Thomas, Ph.D. David A. Tipton, D.D.S., Ph.D.
Biofilm, Amine Oxide
Denture-related stomatitis (DRS) is the most common oral disease affecting denture wearers today, and is characterized by inflammation of the denture bearing mucosa. In a search through historical dental literature for the most often suspected culprit of DRS, one will repeatedly find first listed the fungus Candida albicans. While C. albicans can be isolated from the fitting surfaces of dentures, and the supporting mucosa of patients suffering from DRS, it is also found in the oral cavity of 65% of the human population—most of which is free from oral disease. A truth puzzling to investigators, the discovery of a self-produced, protective matrix present around colonies of communal bacteria and fungi (or biofilm) began to shed light on that troubling finding.
Various investigators have shown that fungal cells in a biofilm community tend to be more resistant to anti-fungal agents than freshly grown cells. Further, it is has been shown that organisms thrive in a biofilm environment, and can behave differently than when they are out of the community. It is not clearly understood, however, why these changes occur. Regardless, C. albicans and its cell components can elicit stimulation of inflammatory cytokines by human monocytes, in vitro, and it is believed that this interaction with monocytes likely leads to the gingival inflammation evident in DRS.
Post-infection therapies for DRS are known to the profession. Prescription antifungal creams alone or in combination with tissue conditioning are tried-and-true methods of treating DRS, however, effective preventive interventions are not readily available. If found, preventive therapy initiated before the onset of DRS could prevent the most common disease affecting denture wearers today.
The current study focused on the influence of the surfactant amine oxide (AO) on fresh C. albicans and C. albicans cultured from biofilms, and the subsequent impact of that interaction on human monocyte production of IL-1β and TNF-α. This study also addressed the impact that AO has on biofilm formation by examining the viability of cells cultured from that AO-modified matrix. If found effective, AO may be valuable in preventing or reducing the incidence of DRS mediated by the fungal pathogen C. albicans. Elucidating the differences between the interaction of fresh and biofilm grown C. albicanswith human monocytes will help clarify the specific host response to this fungal pathogen and shed light on its effect on the chemical mediators of DRS.
Currently, chemical biocides are used to control microbial growth and plaque accumulation. Those agents include sodium hypochlorite and various surfactants. As previously mentioned, this study assessed the antifungal activity of the surfactant AO. The hypotheses of this study are: (1) AO is fungistatic and fungicidal against C. albicans; (2) AO will prevent or reduce fungal biofilm formation on denture acrylic surfaces; and (3) biofilm grown C. albicans will stimulate human monocytes to secrete a greater amount of inflammatory cytokines than cells derived from fresh culture.
Results of this study indicate a significant difference in both viability and monocyte stimulatory ability following exposure to AO between both fresh and biofilm-cultured cells. The degree of AO activity was found to be time and concentration dependent as higher concentrations of AO and higher exposure times to AO were found more effective at killing fungal cells. Further, AO was found effective in altering some protective characteristic of biofilms. The presence of the surfactant during matrix formation rendered inhabitant cells more subject to AO’s antifungal activity than cells cultured from biofilms allowed to develop outside the presence of AO.
These results suggest that AO is effective at reducing the number of viable C. albicans cells isolated from fresh and biofilm culture, as well as fungal cells located in a biofilm environment. Further, this series of experiments suggest that by reducing the number of viable fungal cells, AO is also capable of indirectly decreasing the activity of human monocytes to release the inflammatory cytokines IL-1β and TNF-α. Future investigations should address the intraoral applications of AO, and its effectiveness in a clinical setting.
Hart, Jonathan Michael , "The Influence of Biofilm on the Antifungal Activity of Amine Oxide" (2009). Theses and Dissertations (ETD). Paper 108. http://dx.doi.org/10.21007/etd.cghs.2009.0126.