Candida Species Survival Strategies: New Approaches

Introduction

Candida species, e.g., Candida albicans, Candida glabrata, Candida dubliniensis, and Candida parapsilosis, are colonizers of human host. Under certain circumstances these species can cause infections ranging from superficial to life-threatening disseminated candidiasis [1, 2]. However, discovered in 2009 in Japan, the species C. auris, which carries numerous virulence factors, such as multiple resistances to antifungal agents, does not have, so far, scientific proof of colonization in humans, only infection [3]. Many factors contribute to the occurrence of fungal infections, in particular those caused by Candida. It is possible to list: cancer, co-infections (COVID-19), changes in the immune system (whether acquired or congenital), invasive medical procedures, catheters, mechanical ventilation, prolonged, hyperglycemia, treatment with extensive antimicrobial factors, prolonged use of antimicrobials, among others [4]. The success of C. albicans, the most prevalent and best studied Candida species, as both human pathogen and commensal depends on its genetic, biochemical, and morphological flexibility which facilitates adaptation to a wide range of biotic and abiotic environments.Furthermore, in many host niches Candida cells coexist with members of the human microbiota. The resulting fungal–bacterial interactions have a major influence on the success of C. albicans as commensal and also influence disease development and outcome [1].

The ability of Candida species to infect the host is supported by multiple virulence factors, which include the ability to transition morphologically between yeast forms and hyphae (polymorphism), formation of an extracellular polymer matrix (biofilm/slime) and the expression of adhesins and several hydrolytic enzymes, such as hemolysins, proteases and phospholipases [5, 6, 7]. The polymorphism guarantees the fungus survival in stressful conditions in the environment (osmotic changes, dehydration and temperature changes), protects the cell from the immune defense of the host and is responsible for its adhesion in living tissues [8]. Adhesins are also involved in the process of adhering to the host tissue, facilitating colonization, penetration and invasion [8]. Growing in biofilm, microorganisms may present resistance to antifungals used in medical routine, contributing to therapeutic failure [7]. Hydrolytic enzymes promote the rupture of the host cell membrane, facilitating invasion to the host cell, including mucous membranes and blood vessels. They also act by avoiding the host’s immune response [9].

Among clinical isolates of Candida, antifungal resistance is an important virulence factor. Although some species, such as C. krusei, present natural or intrinsic resistance to antifungals used in routine medicine, an increase in acquired resistance to these drugs has been observed [2]. This phenomenon may be associated with formation of biofilms, hindering or preventing the action of antifungals, presence of genes encoding enzymes capable of blocking the pharmacological action of these drugs, production of efflux pump, alteration of drug binding target, among others [7, 8, 9, 10]. However, this therapeutic failure observed in vivo may also be related to other factors, such as: natural selection; indiscriminate/irrational use of antifungals; inaccurate laboratory diagnosis; in addition to prescribing inappropriate drug therapy [11].

Conclusion

Given the above, it is extremely important to know the factors and mechanisms of pathogenicity in Candida species, because these microorganisms are capable of causing infections ranging from superficial to systemic and life-threatening. As knowledge about pathogenicity in Candida increases, so does the possibility of prevention, and thus opportunities are designed to develop diagnostic and therapeutic tools.