Chapter 19 : From Biology to Drug Development: New Approaches to Combat the Threat of Fungal Biofilms

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Advances in modern medicine are prolonging the lives of severely ill individuals; however, at the same time they are creating an expanding population of compromised patients at increased risk of suffering from invasive fungal infections ( ). These include surgical, transplant, cancer, intensive care unit, and HIV-infected patients, as well as neonates. The use of broad-spectrum antibiotics, parenteral nutrition, medical implant devices, and immune suppression, as well as disruption of mucosal barriers due to surgery, chemotherapy, and radiotherapy represent the most important predisposing factors for these infections. Unfortunately, the mortality rates associated with these fungal infections remain unacceptably high, which clearly points to the many limitations of current antifungal therapy, including the limited armamentarium of antifungal agents, their inherent toxicity, and the emergence of resistance ( ). Fungi are eukaryotic organisms, and there is a paucity of selective targets which can be exploited for antifungal drug development, while at the same time this is also the main reason for the elevated toxicity of some of the current agents ( ). Only three classes of antifungal agents—azoles, polyenes, and echinocandins—constitute the mainstay of antifungal therapy for patients with life-threatening invasive fungal infections. Moreover, the antifungal drug pipeline is mostly dry and, with the exception of isavuconazole, no new agents are expected to reach the market any time soon ( ).

Citation: Pierce C, Srinivasan A, Ramasubramanian A, López-Ribot J. 2015. From Biology to Drug Development: New Approaches to Combat the Threat of Fungal Biofilms, p 373-388. In Ghannoum M, Parsek M, Whiteley M, Mukherjee P (ed), Microbial Biofilms, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MB-0007-2014
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Images depicting the BChip as a new technology platform for microbial culture at the nanoscale level. The technique allows for a variety of high-throughput applications, including ultra-high-throughput drug screening.

Citation: Pierce C, Srinivasan A, Ramasubramanian A, López-Ribot J. 2015. From Biology to Drug Development: New Approaches to Combat the Threat of Fungal Biofilms, p 373-388. In Ghannoum M, Parsek M, Whiteley M, Mukherjee P (ed), Microbial Biofilms, Second Edition. ASM Press, Washington, DC. doi: 10.1128/microbiolspec.MB-0007-2014
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