chapter  13
40 Pages

Hsp90 Governs Dispersion and Drug Resistance of Fungal Biofi lms

In recent decades, fungal pathogens have emerged as a predominant cause of human disease, especially in immunocompromised individuals. The number of acquired fungal bloodstream infections has increased by ~207% in this timeframe [1], [2], [3]. Although diverse species are capable of causing infection, a few prevail as the most prevalent cause of disease. Candida and Aspergillus species together account for ~70% of all invasive fungal infections, with Candida albicans and Aspergillus fumigatus prevailing as the leading causal agents of opportunistic mycoses [2]. Candida species are the fourth leading cause of hospital acquired bloodstream infections in the United States with mortality rates estimated at 40% [4], [5]. The profound economic consequences of Candida infections can be demonstrated by the ~$1.7 billion spent annually on treating candidemia in the United States alone [6]. Further, A. fumigatus is the most common

etiological agent of invasive aspergillosis, with a 40-90% mortality rate [7]. In patients with pulmonary disorders such as asthma or cystic fibrosis, A. fumigatus infection can cause allergic bronchopulmonary aspergillosis leading to severe complications. For these fungal species, there are numerous factors that contribute to the pathogenicity and recalcitrance of resulting infections to antifungal treatment, including the ability to evolve and maintain resistance to conventional antifungal therapy [1].