Editorial [ Biology & Pathology of Human Fungal Pathogens (Guest Editor: Karl Kuchler)]

Fungal infections constitute an ever-growing and significant medical problem in the world. The major fungal pathogens affecting humans include Candida species (such as C. albicans, C. glabrata, C. parapsilosis and C. tropicalis) and Aspergillus spp. (mainly A. fumigatus). Fungal diseases include simple toe nail infections, deepseated and recurrent vaginitis, as well as life-threatening systemic mycoses in patients with impaired immune systems. Hence, individuals with organ or bone marrow transplants, acquired immune deficiency syndrome, those undergoing intensive chemotherapy regimens, neonates and infants, as well as long-term hospitalized and intensive care unit patients are at very high risk to contract fungal infections. Candida species are the most frequent causes, representing the fourth leading cause of hospital-acquired diseases. Several hundred thousand cases are reported worldwide every year, about 70% of which are caused by Candida spp., and 20% by Aspergillus spp. Aspergillosis, affecting up to 25% of all leukemic patients, is the most frequent invasive mould worldwide with a mortality exceeding 90%. The overall mortality of about 35% just for candidemias, exceeds that of all Gram-negative bacterial septicaemias. Moreover, the incidence of systemic infections is rising, partly because improved clinical procedures are also leading to better survival of critically ill patients. The consequences and costs for health-care budgets are enormous, also since fungal infections significantly extend the average length of patient stays in hospitals. The stunning high mortalities of aspergilloses and candidemias are in part due to a lack of accurate and speedy diagnostic tests, but also because current antifungal therapies are not always effective enough. Diagnosis is further complicated by emergence of new and less prevalent pathogens, with Cryptococcus neoformans, Trichophyton spp., Microsporum spp. Epidermophyton spp. and Fusarium spp acting as the main culprits. Taken together, systemic mycoses are serious medical conditions, demanding permanent attention not only in a clinical setting, but also in antifungal drug discovery, as well as in basic research addressing the molecular pathology and mechanisms of disease progression. Therefore, this special issue, which includes six chapters, provides a comprehensive overview on the biology and pathology of major fungal pathogens, covering all aspects from epidemiology to molecular mechanisms of antifungal resistance and pathogenicity. One chapter shall discuss epidemiology related to the prevalence, distribution and frequency of fungal infections and their causative species. Another chapter will delineate state-ofthe- art methods for the clinical diagnosis and therapy of mycoses in various clinical settings. Further, the cell wall is a barrier not only protecting fungi, but also mediating adhesion to host cells, thereby enabling subsequent tissue penetration. Hence, one chapter shall discuss the role of cell wall and its components in pathogenicity, as well as suitability as target for drug discovery. Tissue penetration, invasion, the bypass of a residual immune surveillance and spread are major steps during manifestation of systemic disease, yet we have a limited understanding of how mycoses actually progress in vivo. Thus, one chapter describes the molecular routes of host cell invasion, including a description of animal models used for studies on pathogenicity. Moreover, biofilms, as formed by certain pathogens, can constitute serious clinical complications, since they display intrinsic resistance to antifungal drugs. Approaches to better understand their fomation and role in systemic disease are therefore discussed in another chapter. Finally, a chapter on molecular mechanisms of antifungal resistance phenomena, including those caused by membrane-bound drug efflux pumps, will complete this special section on the biology and pathology of fungal pathogens. Since all chapters were written by leaders in the respective field, I am confident that this all-in-one issue will be attractive for students, researchers, newcomers, as well as clinicians working in the field of infectious diseases caused by human fungal pathogens.