Abstract

Invasive Candidiasis (IC) presents a global mortality rate greater than 40%, occupying the fourth place worldwide as the most frequent opportunistic nosocomial disease. Although the genus Candida consists of around 200 species, only 20 are reported as etiological agents of IC, being Candida albicans the most frequent causal agent. Even when there is a broad range of antifungals drugs for Candida infections, azoles, polyenes, and echinocandins are considered among the most effective treatment. However, there is some incidence for antifungal resistance among some Candida strains, limiting treatment options. Several molecular mechanisms with antifungal agents have been reported for C. albicans where insertions, deletions, and point mutations in genes codifying target proteins are frequently related to the antifungal drug resistance. Furthermore, gene overexpression is also frequently associated to antifungal resistance as well as an increase in the activity of proteins that reduce oxidative damage. This chapter summarizes the main molecular mechanisms to C. albicans antifungal drug resistance, besides offering an overview of new antifungal agents and new antifungal targets to combat fungal infections.

Highlights

  • Candida albicans is the most important opportunistic commensal yeast that asymptomatically colonizes the skin, oral cavity, gastrointestinal and genitourinary tracts in healthy people

  • There are at least 15 Candida species related to human disease, more than 90% of the invasive diseases are related to C. albicans, Candida glabrata, Candida tropicalis, Candida parapsilosis, and Candida krusei [4–6]

  • The following chapter offers an overview of the main genetic mechanisms contributing to the antifungal resistance in C. albicans, besides giving an approach for alternative-compounds proposed against their infection

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Summary

Introduction

Candida albicans is the most important opportunistic commensal yeast that asymptomatically colonizes the skin, oral cavity, gastrointestinal and genitourinary tracts in healthy people It can cause superficial and invasive infections, especially in immunocompromised individuals [1–3]. The most widely used antifungal drugs for IC include: A) azoles, for instance fluconazole (FLZ), itraconazole (ITC), voriconazole, posaconazole, isavuconazole; B) polyenes such as amphotericin B (AMB); C) echinocandins like caspofungin, micafungin, and anidulafungin [9–11]. These antifungal compounds act on different parts of the fungal cell (Figure 1). The following chapter offers an overview of the main genetic mechanisms contributing to the antifungal resistance in C. albicans, besides giving an approach for alternative-compounds proposed against their infection

Azoles
Mutations of the ERG11 target enzyme
Dysregulation of the target enzyme ERG11
Alteration of the ergosterol biosynthesis pathway (point mutations in ERG genes)
Efflux pumps
Polyenes
Alteration in the composition of sterols in the cell membrane (mutations in ERG genes)
Response to oxidative stress and alterations in the cell wall
Echinocandins
Acquired FKS mutations
Adaptive stress responses
New antifungals
Discovery and development of new antifungal drugs
New targets and alternative approaches
Findings
Conclusions
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