Opportunistic yeast pathogens: reservoirs, virulence mechanisms, and therapeutic strategies

Abstract

Life-threatening invasive fungal infections are becoming increasingly common, at least in part due to the prevalence of medical interventions resulting in immunosuppression. Opportunistic fungal pathogens of humans exploit hosts that are immunocompromised, whether by immunosuppression or genetic predisposition, with infections originating from either commensal or environmental sources. Fungal pathogens are armed with an arsenal of traits that promote pathogenesis, including the ability to survive host physiological conditions and to switch between different morphological states. Despite the profound impact of fungal pathogens on human health worldwide, diagnostic strategies remain crude and treatment options are limited, with resistance to antifungal drugs on the rise. This review will focus on the global burden of fungal infections, the reservoirs of these pathogens, the traits of opportunistic yeast that lead to pathogenesis, host genetic susceptibilities, and the challenges that must be overcome to combat antifungal drug resistance and improve clinical outcome.

Influence of Experimental Cryptococcal Meningitis in Wistar Rats on Voriconazole Brain Penetration Assessed by Microdialysis

“…Despite its universally recognized toxicity, amphotericin B was considered to be the cornerstone for successful therapy in cryptococcal meningitis (1). The less toxic agent fluconazole (FCZ) offered an attractive alternative in the treatment of cryptococcosis and a variety of other invasive fungal infections in nonneutropenic patients (2,3); however, its use is limited due to resistance of Cryptococcus spp.…”

Spatial landmarks regulate a Cdc42-dependent MAPK pathway to control differentiation and the response to positional compromise

“…Cell polarity is also reorganized during filamentous/invasive/pseudohyphal growth, which occurs in response to nutrient limitation (glucose or nitrogen), and which results in the formation of branched chains of interconnected cells (14)(15)(16). Many fungal species undergo filamentous growth, and in some species of pathogenic microorganisms, filamentous growth is required for virulence (17). In yeast, the change in polarity during filamentous growth is striking in haploid cells, which switch from axial to distal-unipolar budding (15,18).…”

Calcineurin in fungal virulence and drug resistance: Prospects for harnessing targeted inhibition of calcineurin for an antifungal therapeutic approach

“…1,2 Adding to this complexity are the insufficient therapeutic options available for these invasive fungal infections due to the limited number of antifungal drugs, their toxicity and the emergence of drug resistance. [3][4][5][6] There is a critical need for new antifungal agents with broad spectrum antifungal activity, little or no drug resistance, and reduced adverse effects compared to currently available drugs.…”