Biofilms in Dermatology
Candida albicans (C. albicans) is a dimorphic yeast that typically exists in a commensal state on mucocutaneous surfaces. In the setting of predisposing factors such as immunosuppression, systemic antibiotic therapy, endocrinopathies, excessive moisture, or ill-fitting dentures, this organism becomes an opportunistic pathogen causing local infections of the skin, nails, and mucous membranes, and in some cases disseminated systemic disease. Recent in vivo animal models demonstrate the ability of C. albicans to form biofilms on mucosal surfaces suggesting that biofilm formation and its characteristic tissue adherence play a key role in promoting Candida infections in these sites. Although it has been suggested that C. albicans forms mucosal biofilms when there are changes in host immunity or alterations in the mucosal ecology or integrity, it is unknown if this organism always exists as a biofilm, even in its commensal state. Cutaneous Candida infections such as intertrigo and onychomycosis may also involve biofilm-associated organisms, although this has not been studied. Oropharyngeal candidiasis (OPC) is seen in 5% of newborns, 10% of the elderly, and is the most common opportunistic infection in AIDS, affecting 90% of these patients. Acute pseudomembranous candidiasis, or thrush, is a common clinical presentation with its characteristic white plaques presumably due to biofilm formation. In a murine OPC model, BCR1, the master transcription factor for Candida biofilms, was shown to be involved in attachment to host cells, promoting epithelial invasion, and protecting C. albicans from neutrophilic attack. C. albicans biofilms have also been shown to overexpress the cell wall polysaccharide, β-glucan, which may be involved in regulating the host immune response and promoting antifungal resistance. Chronic atrophic candidiasis, also known as denture stomatitis, is seen in up to 70% of denture wearers and is caused by ill-fitting dentures compromising what is normally an effective mucosal barrier. Denture stomatitis can be directly linked to biofilm formation as dentures are abiotic surfaces that have been demonstrated to harbor C. albicans biofilms. Angular cheilitis is commonly seen in patients with denture stomatitis, suggesting that biofilms may also play a role in this type of infection. While routine and uncomplicated candidiasis typically responds to treatment with traditional antifungals such as the azoles, the ineffectiveness of these agents in recurrent and persistent Candida infections is thought to result from the presence of biofilms. Most of the information regarding Candida biofilm drug resistance stems from in vitro studies, yet these findings are likely applicable to the clinical setting, as in vitro and in vivo C. albicans biofilms have similar architectural structure, growth kinetics, and genetic determinants. Candida biofilms exhibit a 30 to 2000 fold increase in resistance to amphotericin B, fluconazole, itraconazole, and ketoconazole as compared to planktonic organisms. Subpopulations of cells that exhibit extremely high levels of antifungal resistance as well as the drug penetration barrier function of the EPS have been demonstrated in C. albicans biofilms. Recently developed antifungal agents such as the echinocandins and liposomal formulations of amphotericin B have been shown to be effective against C. albicans biofilms, but are currently available only for intravenous administration. Gentian violet has shown efficacy on in vitro isolates from OPC lesions and may act by inhibiting germination and forming radicals, which enhance penetration through the biofilm matrix. Additional therapeutic strategies that may hold promise for the treatment of Candida biofilm infections include quorum sensing inhibitors, vaccines, anti-candidal antibodies, cytokine therapy, and specific inhibitors of BCR1 and its target genes.
Candidiasis
Candida albicans (C. albicans) is a dimorphic yeast that typically exists in a commensal state on mucocutaneous surfaces. In the setting of predisposing factors such as immunosuppression, systemic antibiotic therapy, endocrinopathies, excessive moisture, or ill-fitting dentures, this organism becomes an opportunistic pathogen causing local infections of the skin, nails, and mucous membranes, and in some cases disseminated systemic disease. Recent in vivo animal models demonstrate the ability of C. albicans to form biofilms on mucosal surfaces suggesting that biofilm formation and its characteristic tissue adherence play a key role in promoting Candida infections in these sites. Although it has been suggested that C. albicans forms mucosal biofilms when there are changes in host immunity or alterations in the mucosal ecology or integrity, it is unknown if this organism always exists as a biofilm, even in its commensal state. Cutaneous Candida infections such as intertrigo and onychomycosis may also involve biofilm-associated organisms, although this has not been studied. Oropharyngeal candidiasis (OPC) is seen in 5% of newborns, 10% of the elderly, and is the most common opportunistic infection in AIDS, affecting 90% of these patients. Acute pseudomembranous candidiasis, or thrush, is a common clinical presentation with its characteristic white plaques presumably due to biofilm formation. In a murine OPC model, BCR1, the master transcription factor for Candida biofilms, was shown to be involved in attachment to host cells, promoting epithelial invasion, and protecting C. albicans from neutrophilic attack. C. albicans biofilms have also been shown to overexpress the cell wall polysaccharide, β-glucan, which may be involved in regulating the host immune response and promoting antifungal resistance. Chronic atrophic candidiasis, also known as denture stomatitis, is seen in up to 70% of denture wearers and is caused by ill-fitting dentures compromising what is normally an effective mucosal barrier. Denture stomatitis can be directly linked to biofilm formation as dentures are abiotic surfaces that have been demonstrated to harbor C. albicans biofilms. Angular cheilitis is commonly seen in patients with denture stomatitis, suggesting that biofilms may also play a role in this type of infection. While routine and uncomplicated candidiasis typically responds to treatment with traditional antifungals such as the azoles, the ineffectiveness of these agents in recurrent and persistent Candida infections is thought to result from the presence of biofilms. Most of the information regarding Candida biofilm drug resistance stems from in vitro studies, yet these findings are likely applicable to the clinical setting, as in vitro and in vivo C. albicans biofilms have similar architectural structure, growth kinetics, and genetic determinants. Candida biofilms exhibit a 30 to 2000 fold increase in resistance to amphotericin B, fluconazole, itraconazole, and ketoconazole as compared to planktonic organisms. Subpopulations of cells that exhibit extremely high levels of antifungal resistance as well as the drug penetration barrier function of the EPS have been demonstrated in C. albicans biofilms. Recently developed antifungal agents such as the echinocandins and liposomal formulations of amphotericin B have been shown to be effective against C. albicans biofilms, but are currently available only for intravenous administration. Gentian violet has shown efficacy on in vitro isolates from OPC lesions and may act by inhibiting germination and forming radicals, which enhance penetration through the biofilm matrix. Additional therapeutic strategies that may hold promise for the treatment of Candida biofilm infections include quorum sensing inhibitors, vaccines, anti-candidal antibodies, cytokine therapy, and specific inhibitors of BCR1 and its target genes.
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