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Fungal Pathogenesis in Humans: The Growing Threat

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ISBN: 9783038979005 / 9783038979012 Year: Pages: 232 DOI: 10.3390/books978-3-03897-901-2 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology --- Genetics
Added to DOAB on : 2019-06-26 08:44:06
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Cancer survival rates and successful organ transplantation in patients continues to increase due to improvements in early diagnosis and treatments. Since immuno-suppressive therapies are frequently used, the mortality rate due to secondary infections has become an ever-increasing problem. Opportunistic fungal infections are probably the deadliest threat to these patients due to their difficult early diagnosis, the limited effect of antifungal drugs and the appearance of resistances. In recent years, a considerable effort has been devoted to investigating the role of many virulence traits in the pathogenic outcome of fungal infections. New virulence factors (hypoxia adaptation, CO2 sensing, pH regulation, micronutrient acquisition, secondary metabolites, immunity regulators, etc.) have been reported and their molecular mechanisms of action are being thoroughly investigated. The recent application of gene-editing technologies such as CRISPr-Cas9, has opened a whole new window to the discovery of new fungal virulence factors. Accurate fungal genotyping, Next Generation Sequencing and RNAseq approaches will undoubtedly provide new clues to interpret the plethora of molecular interactions controlling these complex systems. Unraveling their intimate regulatory details will provide insights for a more target-focused search or a rational design of more specific antifungal agents. This Special Issue is show significant discoveries, proofs of concept of new theories or relevant observations in fungal pathogenesis and its regulation.

Carbonic Anhydrases and Metabolism

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ISBN: 9783038978008 9783038978015 Year: Pages: 184 DOI: 10.3390/books978-3-03897-801-5 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2019-04-25 16:37:17
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Carbonic anhydrases (CAs; EC 4.2.1.1) are metalloenzymes present in all kingdoms of life, as they equilibrate the reaction between three simple but essential chemical species: CO2, bicarbonate, and protons. Discovered more than 80 years ago, in 1933, these enzymes have been extensively investigated due to the biomedical application of their inhibitors, but also because they are an extraordinary example of convergent evolution, with seven genetically distinct CA families that evolved independently in Bacteria, Archaea, and Eukarya. CAs are also among the most efficient enzymes known in nature, due to the fact that the uncatalyzed hydration of CO2 is a very slow process and the physiological demands for its conversion to ionic, soluble species is very high. Inhibition of the CAs has pharmacological applications in many fields, such as antiglaucoma, anticonvulsant, antiobesity, and anticancer agents/diagnostic tools, but is also emerging for designing anti-infectives, i.e., antifungal, antibacterial, and antiprotozoan agents with a novel mechanism of action. Mitochondrial CAs are implicated in de novo lipogenesis, and thus selective inhibitors of such enzymes may be useful for the development of new antiobesity drugs. As tumor metabolism is diverse compared to that of normal cells, ultimately, relevant contributions on the role of the tumor-associated isoforms CA IX and XII in these phenomena have been published and the two isoforms have been validated as novel antitumor/antimetastatic drug targets, with antibodies and small-molecule inhibitors in various stages of clinical development. CAs also play a crucial role in other metabolic processes connected with urea biosynthesis, gluconeogenesis, and so on, since many carboxylation reactions catalyzed by acetyl-coenzyme A carboxylase or pyruvate carboxylase use bicarbonate, not CO2, as a substrate. In organisms other than mammals, e.g., plants, algae, and cyanobacteria, CAs are involved in photosynthesis, whereas in many parasites (fungi, protozoa), they are involved in the de novo synthesis of important metabolites (lipids, nucleic acids, etc.). The metabolic effects related to interference with CA activity, however, have been scarcely investigated. The present Special Issue of Metabolites aims to fill this gap by presenting the latest developments in the field of CAs and their role in metabolism.

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