Antifungals : From Genomics to Resistance and the Development of Novel Agents.

Intro -- Contents -- Contributors -- Preface -- 1: Molecular Mechanisms of Resistance of Candida spp. to Membrane-targeting Antifungals -- Introduction -- Azoles -- Non-azole ergosterol biosynthesis inhibitors -- Polyenes -- Concluding remarks -- 2: Point Mutations and Membrane-targeting Antifungal Resistance in Aspergillus fumigatus and Other Non-Candida Species -- Introduction -- Aspergillus fumigatus azole resistance in clinical settings -- The molecular target of azoles, allylamines and polyenes: ergosterol and ergosterol biosynthesis pathway -- Differences in ergosterol pathway between Aspergillus spp. and yeasts -- Fungal 14-a sterol demethylases (SDMs): the main target for azole antifungals -- A. fumigatus azole susceptibility patterns and mechanisms of azole resistance linked with CYP51 point mutations -- Azole resistance in non-fumigatus Aspergillus -- Azole secondary resistance linked with point mutations in the 14-α sterol demethylase enzyme in non-Candida and non-Aspergillus species -- Polyene resistance -- Resistance to allylamines -- General conclusion -- 3: Echinocandins: Resistance Mechanisms -- Introduction -- Structures -- Echinocandin target: Fks1 -- Fks gene family -- Fks1 structure-function -- Cell-free β-1,3-glucan synthase systems -- Echinocandin uptake and efflux -- Acquired echinocandin resistance: Fks hot spots 1 and 2 -- Differential echinocandin resistance: discovery of hot spot 3 -- Impact of Fks heterozygosity and redundancy on acquired resistance -- Fks-independent acquired echinocandin resistance -- Intrinsic echinocandin resistance: hot spot 1 substitutions -- Intrinsic echinocandin resistance: hot spot 3 substitutions -- Intrinsic resistance: mechanism to be determined -- Stage-specific intrinsic resistance -- Conclusions and future prospects -- 4: Biofilms and Antifungal Resistance.

Introduction to fungal biofilms -- Fungal biofilm infections of humans -- Current standard of care for fungal biofilm infections -- Mechanisms of fungal biofilm drug resistance -- Challenges and strategies to developing therapeutics for fungal biofilm infections -- 5: Drug Combinations as a Strategy to Potentiate Existing Antifungal Agents -- Introduction -- In vitro and in vivo combinations with known antifungal agents -- In vitro and in vivo combinations of non-antifungals with known antifungal agents -- Systematic drug combination screenings -- Chemogenetic approaches in the exploration of drug interaction mechanisms -- Conclusions -- 6: Approaches to Detect Alternative Mechanisms of Resistance to Systemic Antifungals -- Introduction -- 'Omics' approaches -- Mutants collections screening -- Comparison with others species -- Concluding remarks -- 7: New Antifungal Discovery from Existing Chemical Compound Collections -- Introduction -- A new career for acetylsalicylic acid as an antifungal -- Other non-traditional antimicrobial agents -- Conclusion and future perspectives -- 8: Exploring New Insights into Fungal Biology as Novel Antifungal Drug Targets -- Introduction -- Fungal CO2 sensing -- Inhibition of fungal cell wall biosynthesis -- Quorum sensing molecules as potential antifungals -- Intracellular proliferation -- Antimicrobial peptides -- Summary -- 9: Strategies for the Identification of the Mode of Action of Antifungal Drug Candidates -- Introduction -- Mode-of-action studies of currently used antifungal agents: a historical perspective -- Chemical genetics and chemogenomics strategies for the identification of the mode-of-action of antifungal drug candidates: a high-throughput reverse-genetics approach -- Biochemical and pharmacological approaches exploring drug-target physical associations -- Clues from transcriptomics analyses.

High-throughput imaging -- Concluding remarks -- 10: Genome Integrity: Mechanisms and Contribution to Antifungal Resistance -- Introduction -- Genomic alterations involved in the acquisition of antifungal resistance -- Molecular mechanisms that suppress genome instability -- The effect of drug resistance acquisition on fitness -- Conclusions and perspectives -- 11: Modulation of the Host Response to Control Invasive Fungal Infections -- Introduction -- Risk factors for invasive fungal infections -- Interplay between fungi and host immune cells -- Restoration of the immune system -- Conclusion -- 12: Antifungal Vaccines and Immunotherapeutics -- Introduction: the host-fungus interaction -- Immune response to fungi -- Antifungal vaccination -- Concluding remarks -- 13: Animal Models to Study Fungal Virulence and Antifungal Drugs -- Mouse: the model of choice -- Mini-host models -- Conclusions -- Current Books of Interest -- Index.

In this book a panel of high-profile authors provides an overview of current antifungal research. Chapters are written from a molecular and genomic perspective and contain speculative models upon which to base future research efforts. Topics include: the molecular mechanisms responsible for antifungal resistance to the classical molecules, azoles, polyenes, and echinocandins; fungal biofilms; fungal-specific biological pathways that constitute potential new targets; strategy to potentiate existing antifungal agents; Impact of high throughput screenings of chemical compound collections; modulating the host response; antifungal vaccines; and animals models. This volume is an essential reference for everyone with an interest in fungal pathogenesis. A recommended book for all biology and medical libraries.

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Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, 2024. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries.