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Virulence factors of medically important fungi
L H Hogan1, B S Klein, S M Levitz
1Department of Pediatrics, University of Wisconsin Medical School, USA. lhhogan@facstaff.wisc.edu
Abstract:
Human fungal pathogens have become an increasingly important medical problem with the explosion in the number of immunocompromised patients as a result of cancer, steroid therapy, chemotherapy, and AIDS. Additionally, the globalization of travel and expansion of humankind into previously undisturbed habitats have led to the reemergence of old fungi and new exposure to previously undescribed fungi. Until recently, relatively little was known about virulence factors for the medically important fungi. With the advent of molecular genetics, rapid progress has now been made in understanding the basis of pathogenicity for organisms such as Aspergillus species and Cryptococcus neoformans. The twin technologies of genetic transformation and "knockout" deletion construction allowed for genetic tests of virulence factors in these organisms. Such knowledge will prove invaluable for the rational design of antifungal therapies. Putative virulence factors and attributes are reviewed for Aspergillus species, C. neoformans, the dimorphic fungal pathogens, and others, with a focus upon a molecular genetic approach. Candida species are excluded from coverage, having been the subject of numerous recent reviews. This growing body of knowledge about fungal pathogens and their virulence factors will significantly aid efforts to treat the serious diseases they cause.
Insights
Human fungal pathogens pose a growing threat, especially to immunocompromised individuals. Molecular genetics advances are revealing fungal virulence factors, aiding the development of new antifungal therapies.
Area of Science:
- Medical Mycology
- Molecular Biology
- Infectious Diseases
Background:
- Increasing incidence of immunocompromised patients (cancer, chemotherapy, AIDS) fuels fungal infections.
- Globalization and habitat changes lead to re-emerging and novel fungal exposures.
- Limited understanding of fungal virulence factors until recent molecular advancements.
Purpose of the Study:
- To review current knowledge on fungal virulence factors.
- To highlight the role of molecular genetics in understanding fungal pathogenicity.
- To inform the rational design of novel antifungal treatments.
Main Methods:
- Focus on molecular genetic approaches, including genetic transformation and gene deletion ('knockout') studies.
- Review of virulence factors in key fungal pathogens like Aspergillus species and Cryptococcus neoformans.
- Exclusion of Candida species due to extensive recent reviews.
Main Results:
- Molecular genetics has significantly advanced the understanding of fungal pathogenicity.
- Identification of specific virulence factors in Aspergillus and Cryptococcus species.
- Demonstration of the utility of genetic manipulation in testing virulence factors.
Conclusions:
- Understanding fungal virulence factors is crucial for combating serious infections.
- Molecular genetic insights are paving the way for more effective antifungal drug design.
- Continued research into fungal pathogens and their virulence mechanisms is essential.