Fungi pathogenic to humans: molecular bases of virulence of Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus.

Abstract

The frequency of severe systemic fungal diseases has increased in the last few decades. The clinical use of antibacterial drugs, immunosuppressive agents after organ transplantation, cancer chemotherapy, and advances in surgery are associated with increasing risk of fungal infections. Opportunistic pathogens from the genera Candida and Aspergillus as well as pathogenic fungi from the genus Cryptococcus can invade human organism and may lead to mucosal and skin infections or to deep-seated mycoses of almost all inner organs, especially in immunocompromised patients. Nowadays, there are some effective antifungal agents, but, unfortunately, some of the pathogenic species show increasing resistance. The identification of fungal virulence factors and recognition of mechanisms of pathogenesis may lead to development of new efficient antifungal therapies. This review is focused on major virulence factors of the most common fungal pathogens of humans: Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans. The adherence to host cells and tissues, secretion of hydrolytic enzymes, phenotypic switching and morphological dimorphism contribute to C. albicans virulence. The ability to grow at 37 degrees C, capsule synthesis and melanin formation are important virulence factors of C. neoformans. The putative virulence factors of A. fumigatus include production of pigments, adhesion molecules present on the cell surface and secretion of hydrolytic enzymes and toxins.

The effects of gamma radiation, UV and visible light on ATP levels in yeast cells depend on cellular melanization

“…However, it contains a laccase enzyme which is capable of making melanin from a wide variety of substrates (Garcia-Rivera et al 2005). As a consequence, C. neoformans is melanized in infections, and the ability to melanize is an important virulence factor for C. neoformans as well as several other human pathogenic fungi (Karkowska-Kuleta et al 2009). Melanin in C. neoformans is located in the cell wall, and is thought to provide protection from a variety of environmental insults, including UV light, desiccation, toxic metals, and attack by the reactive oxygen species produced by the macrophages (reviewed in Gomez &Casadevall 2003).…”

Role of Macroautophagy in Nutrient Homeostasis During Fungal Development and Pathogenesis

“…An Afatg1 mutant showed compromised sporulation, which could be restored by supplementation of exogenous nitrogen source (ammonium tartrate) [52]. The reason behind variant requirements for autophagy in these four pathogens was discussed systematically in a recent review [89], and was indicated to be based on the difference in the aspects such as the host infection niche and the evolutionary pressures faced by the pathogen species [89], the host signals in response to the pathogen [89], and molecular basis of virulence for each pathogen [90]. …”

Therapeutic efficacy of chitosan against invasive candidiasis in mice

“…An altered balance between the host immunity and this opportunistic fungus, as in the case of immunocompromised patients, is one of the leading causes of candidiasis in humans (Bodey, 1993). After entering the blood stream, the yeast cells can infect all internal organs and may cause life-threatening septicemia (Karkowska-Kuleta et al, 2009). Candidiasis can develop as superficial candidiasis (skin and mucosa) which occurs in healthy individuals, or invasive candidiasis which is seen in cancer patients, AIDS patients, and immunocompromised individuals following transplantation (Larriba et al, 2000).…”