Abcr1mutant that produces hyphae still has a severe biofilm defect inC. of growth of microorganisms in nature. This growth form presumably allows microbial cells to survive in hostile environments, enhances their resistance to physical and chemical pressures, and promotes metabolic cooperation [1]. In fact, it is estimated that approximately 80% of all bacteria in the environment exist in biofilm communities, and more than 65% of human microbial infections involve biofilms [2]. Microbial biofilms are dynamic communities of micro-organisms strongly attached to biologic and nonbiologic substrata that are enclosed in a self-produced protective exopolymeric matrix (EPM) [3]. Furthermore, mixed poly-microbial biofilms are common and can be considered even more complex communities of microbes that cooperatively interact in an altruistic manner [4]. Experts’ desire for studying the role of microbial biofilms in human disease stems from the observation that microbes within biofilms display unique phenotypic characteristics that increase resistance to host immune mechanisms and antimicrobial therapy [5-8]. The successful eradication of biofilms Tyrphostin AG-528 in vivo usually requires harmful concentrations of antibiotics [9]. Although bacterial biofilms have been extensively analyzed since the mid 1980s, little attention was paid to medically relevant fungal biofilms until the past decade. To date, a wide variety of fungi have been shown to colonize surfaces and form biofilms. This review focuses on recent information about fungal biofilms and their relevance in the Tyrphostin AG-528 setting of human disease. == Clinical Importance of Fungal Biofilms == The use of broad spectrum antibiotics and corticosteroids, invasive medical procedures, and the AIDS epidemic are associated with a dramatically increased incidence of invasive fungal diseases, which are inherently hard to treat. The persistence of fungal infections is promoted by the ability of fungi to form biofilms on a wide variety of implanted medical devices [10]. Consequently, fungal biofilms have become a significant clinical and economic problem. Much of our knowledge about fungal biofilm formation has been gained through the studies Tyrphostin AG-528 of biofilms created byCandidaspecies on artificial surfaces [11-13]. Furthermore, the increasing awareness of the importance of fungal biofilms is usually reflected by reports on other yeasts and filamentous fungi, includingCryptococcus neoformans,Aspergillus fumigatus,Fusarium species,Pneumocystis species,Trichosporon asahii,Blastoschizomyces capitatus,Malassezia pachydermatis,Saccharomyces cerevisiae, andCoccidioides immitis[8,14-21]. Candida albicans, a commensal of human mucosal surfaces and an opportunistic pathogen in immunocompromised individuals, is usually generally associated with biofilm formation [22].C. albicansis the third leading cause of infections related to intravascular catheters, with the second highest rate of colonization to contamination and the overall highest crude mortality Rabbit Polyclonal to YOD1 [23,24]. This fungus can colonize prosthetic devices either endogenously or exogenously (Fig. 1). Yeast cells can detach from adherent biofilms around the devices and cause fungemia and systemic contamination. Treatment usually requires removal of the device and a prolonged course of antimicrobial therapy [25], resulting in costs exceeding $50,000 per patient. The number of non-albicans Candidaspecies that exhibit biofilm formation and cause device-related infections is usually rising steadily and thus is usually of great concern.Candidaspecies that cause nosocomial infections includeC. glabrata,C. parapsilosis,C. krusei, andC. tropicalis[26-30]. == Fig. 1. == Scanning electron microscopy image of mature (24-h)Candida albicansbiofilms created on a rat central venous catheter model showed a network comprising yeast Tyrphostin AG-528 cells and hyphae surrounded by moderate amounts of exopolymeric matrix. Bar, 5 m C. neoformansis an encapsulated fungus that causes life-threatening meningoencephalitis in immunocompromised individuals. It colonizes and subsequently forms biofilms on diverse prosthetic devices, including ventricular shunts, peritoneal dialysis fistulas, and cardiac valves [14,31-33]. Such biofilms comprise yeast cells surrounded by vast amounts of polysaccharide (Fig. 2), likely preventing successful eradication. BecauseC. neoformansis Tyrphostin AG-528 an environmental fungus and only an accidental pathogen, it is not amazing that biofilm formation constitutes an important survival strategy in hostile environmental.