The recent progressive increase in the incidence of invasive fungal infections, especially in immunocompromised patients, makes the search for new therapies crucial in the face of the growing drug resistance of prevalent nosocomial yeast strains. The latest research focuses on the active compounds of natural origin, inhibiting fungal growth, and preventing the formation of fungal biofilms. Antimicrobial peptides are currently the subject of numerous studies concerning effective antifungal therapy. In the present study, the antifungal properties of two synthetic peptides (ΔM3, ΔM4) derived from an insect antimicrobial peptide – cecropin D – were investigated. The fungicidal activity of both compounds was demonstrated against the yeast forms of Candida albicans, Candida tropicalis, and Candida parapsilosis, reaching a MFC99.9 in the micromolar range, while Candida glabrata showed greater resistance to these peptides. The scanning electron microscopy revealed a destabilization of the yeast cell walls upon treatment with both peptides; however, their effectiveness was strongly modified by the presence of salt or plasma in the yeast environment. The transition of C. albicans cells from yeast to filamentous form, as well as the formation of biofilms, was effectively reduced by ΔM4. Mature biofilm viability was inhibited by a higher concentration of this peptide and was accompanied by increased ROS production, activation of the GPX3 and SOD5 genes, and finally, increased membrane permeability. Furthermore, both peptides showed a synergistic effect with caspofungin in inhibiting the metabolic activity of C. albicans cells, and an additive effect was also observed for the mixtures of peptides with amphotericin B. The results indicate the possible potential of the tested peptides in the prevention and treatment of candidiasis.
Although Candida species are widespread commensals of the microflora of healthy individuals, they are also among the most important human fungal pathogens that under certain conditions can cause diseases (candidiases) of varying severity ranging from mild superficial infections of the mucous membranes to life-threatening systemic infections. So far, the vast majority of research aimed at understanding the molecular basis of pathogenesis has been focused on the most common species—Candida albicans. Meanwhile, other closely related species belonging to the CTG clade, namely, Candida tropicalis and Candida dubliniensis, are becoming more important in clinical practice, as well as a relatively newly identified species, Candida auris. Despite the close relationship of these microorganisms, it seems that in the course of evolution, they have developed distinct biochemical, metabolic, and physiological adaptations, which they use to fit to commensal niches and achieve full virulence. Therefore, in this review, we describe the current knowledge on C. tropicalis, C. dubliniensis, and C. auris virulence factors, the formation of a mixed species biofilm and mutual communication, the environmental stress response and related changes in fungal cell metabolism, and the effect of pathogens on host defense response and susceptibility to antifungal agents used, highlighting differences with respect to C. albicans. Special attention is paid to common diagnostic problems resulting from similarities between these species and the emergence of drug resistance mechanisms. Understanding the different strategies to achieve virulence, used by important opportunistic pathogens of the genus Candida, is essential for proper diagnosis and treatment.
The oral cavity of humans is colonized by diversity of microbial community, although dominated by bacteria, it is also constituted by a low number of fungi, often represented by Candida albicans. Although in the vast minority, this usually commensal fungus under certain conditions of the host (e.g., immunosuppression or antibiotic therapy), can transform into an invasive pathogen that adheres to mucous membranes and also to medical or dental devices, causing mucosal infections. This transformation is correlated with changes in cell morphology from yeast‐like cells to hyphae and is supported by numerous virulence factors exposed by C. albicans cells at the site of infection, such as multifunctional adhesins, degradative enzymes, or toxin. All of them affect the surrounding host cells or proteins, leading to their destruction. However, at the site of infection, C. albicans can interact with different bacterial species and in its filamentous form may produce biofilms—the elaborated consortia of microorganisms, that present increased ability to host colonization and resistance to antimicrobial agents. In this review, we highlight the modification of the infectious potential of C. albicans in contact with different bacterial species, and also consider the mutual bacterial‐fungal relationships, involving cooperation, competition, or antagonism, that lead to an increase in the propagation of oral infection. The mycofilm of C. albicans is an excellent hiding place for bacteria, especially those that prefer low oxygen availability, where microbial cells during mutual co‐existence can avoid host recognition or elimination by antimicrobial action. However, these microbial relationships, identified mainly in in vitro studies, are modified depending on the complexity of host conditions and microbial dominance in vivo.
Candida albicans is one of the main pathogens responsible for the development of difficult‐to‐fight fungal infections called candidiasis. Neutrophils are the major effector cells involved in the eradication of fungal pathogens. This group of immune cells uses several mechanisms that enable the rapid neutralization of pathogens. The most frequently identified mechanisms are phagocytosis and the release of neutrophil extracellular traps (NETs). The mechanism for selecting the type of neutrophil immune response is still unknown. In our study, we analyzed the relationship between the activation of phagocytosis and netosis. We detected the presence of two neutrophil populations characterized by different response patterns to contact with C. albicans blastospores. The first neutrophil population showed an increased ability to rapidly release NETs without prior internalization of the pathogen. In the second population, the netosis process was inherently associated with phagocytosis. Differences between populations also referred to the production of reactive oxygen species. Our results suggest that neutrophils use different strategies to fight C. albicans and, contrary to previous reports, these mechanisms are not mutually exclusive.
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