Chapter 3. Pathogenesis of Oral Candidiasis: A Virulence Insight into Drug Discovery and New Treatments

Priscilla Guimarães Silva Vasconcelos1, Diego Romário-Silva2, Ernani Canuto Figueirêdo Júnior1, Jozinete Vieira Pereiraand Edja Maria Melo de Brito Costa1
1Department of Dentistry, State University of Paraíba (UEPB), Campina Gande, PB, Brazil
2Research Program in Integrated Dental Sciences, University of Cuiabá (UNIC), Cuiabá, MT, Brazil

Part of the book: The Book of Fungal Pathogens

Abstract

Oral candidiasis is one of the most prevalent infections in humans, an opportunistic infection characterized by the overgrowth of Candida spp. in the superficial epithelium of the oral mucosa. Candida infection may be facilitated by different factors including alterations in systemic, hereditary, local, and environmental conditions. Once installed this clinicopathological condition can present itself in distinct clinical presentations, such as pseudomembranous, acute erythematous, chronic erythematous, angular cheilitis, median rhomboid glossitis, chronic hyperplastic, and linear gingival erythema. The pathogenesis of these distinct oral diseases as well as their severity is related to the microorganismal virulence factors and an infected individual’s immune conditions. The predominant species associated with oral candidiasis is Candida albicans (C. albicans), however other species have also been identified in several studies related to different clinical conditions, including Candida glabrata, Candida krusei, Candida guillermondii, Candida lusitaniae, Candida parapsilosis, Candida dubliniensis, Candida pseudotropicalis, Candida stellatoidea, and Candida tropicalis. Virulence factors of Candida species are related to the establishment of the pathogen in the body and subsequent tissue invasion. The main virulence factors involve the transition from yeast form into hyphae, expression of adhesion and invasion molecules, thigmotropism, secretion of hydrolytic enzymes, and biofilm formation. These factors are potential therapeutic targets in drug development for candidiasis treatment. Nowadays, oral candidiasis treatment relies on a limited arsenal of antifungal agents, utilized topically or systemically. The antifungal medications are divided into three classes according to mode of action and target: polyenes which involve the disruption of fungal cell membranes, azoles which cause inhibition of ergosterol synthesis, and echinocandins which inhibit the synthesis of specific enzymes. However, the paucity of available antifungal classes coupled with the suboptimal selectivity, increased toxicity, and high likelihood of developing drug resistant yeasts has prompted the study and development of alternative therapies such as the use of probiotics, photodynamic therapies, nanoparticles and nanocomposites, and phytotherapy research. Therefore, this chapter aims to discuss the prevalence and pathogenesis of oral candidiasis as well as the available therapeutic options, highlighting the current challenges and future directions for the development of new treatments and the control of this infection.

Keywords: oral candidiasis, Candida spp., virulence factors, antifungal agents, antifungal drug resistance, drug discovery


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