Abstract:The rapid increase in drug-resistant and multidrug-resistant infections poses a serious challenge to antimicrobial therapies, and has created a global health crisis. Since antimicrobial peptides (AMPs) have escaped bacterial resistance throughout evolution, AMPs are a category of potential alternatives for antibiotic-resistant “superbugs”. The Chromogranin A (CgA)-derived peptide Catestatin (CST: hCgA352–372; bCgA344–364) was initially identified in 1997 as an acute nicotinic-cholinergic antagonist. Subsequent… Show more
“…New calcineurin inhibitors were discovered. Among them, there are vasostatin-I which is a peptide derived from chromogranin A, its shorter fragments chromofungin and catestatin, which are active against yeasts and filamentous fungi (Aslam et al 2012 ; Jati et al 2023 ), and tamoxifen, an anticancer that is supposed to interfere in the calcineurin pathway and that synergizes with amphotericin B (Hai et al 2019 ). Fig.…”
Fungal infections represent a serious global health threat. The new emerging pathogens and the spread of different forms of resistance are now hardly challenging the tools available in therapy and diagnostics. With the commonly used diagnoses, fungal identification is often slow and inaccurate, and, on the other hand, some drugs currently used as treatments are significantly affected by the decrease in susceptibility. Herein, the antifungal arsenal is critically summarized. Besides describing the old approaches and their mechanisms, advantages, and limitations, the focus is dedicated to innovative strategies which are designed, identified, and developed to take advantage of the discrepancies between fungal and host cells. Relevant pathways and their role in survival and virulence are discussed as their suitability as sources of antifungal targets. In a similar way, molecules with antifungal activity are reported as potential agents/precursors of the next generation of antimycotics. Particular attention was devoted to biotechnological entities, to their novelty and reliability, to drug repurposing and restoration, and to combinatorial applications yielding significant improvements in efficacy.
Key points
• New antifungal agents and targets are needed to limit fungal morbidity and mortality.
• Therapeutics and diagnostics suffer of delays in innovation and lack of targets.
• Biologics, drug repurposing and combinations are the future of antifungal treatments.
“…New calcineurin inhibitors were discovered. Among them, there are vasostatin-I which is a peptide derived from chromogranin A, its shorter fragments chromofungin and catestatin, which are active against yeasts and filamentous fungi (Aslam et al 2012 ; Jati et al 2023 ), and tamoxifen, an anticancer that is supposed to interfere in the calcineurin pathway and that synergizes with amphotericin B (Hai et al 2019 ). Fig.…”
Fungal infections represent a serious global health threat. The new emerging pathogens and the spread of different forms of resistance are now hardly challenging the tools available in therapy and diagnostics. With the commonly used diagnoses, fungal identification is often slow and inaccurate, and, on the other hand, some drugs currently used as treatments are significantly affected by the decrease in susceptibility. Herein, the antifungal arsenal is critically summarized. Besides describing the old approaches and their mechanisms, advantages, and limitations, the focus is dedicated to innovative strategies which are designed, identified, and developed to take advantage of the discrepancies between fungal and host cells. Relevant pathways and their role in survival and virulence are discussed as their suitability as sources of antifungal targets. In a similar way, molecules with antifungal activity are reported as potential agents/precursors of the next generation of antimycotics. Particular attention was devoted to biotechnological entities, to their novelty and reliability, to drug repurposing and restoration, and to combinatorial applications yielding significant improvements in efficacy.
Key points
• New antifungal agents and targets are needed to limit fungal morbidity and mortality.
• Therapeutics and diagnostics suffer of delays in innovation and lack of targets.
• Biologics, drug repurposing and combinations are the future of antifungal treatments.
“…They summarized this peptide's antibacterial, antifungal, and anti-yeast activity and its N-terminal domain of 15 amino acids called Cateslytin. The author reported the chemically modified isoform for this smaller peptide, with the total D-amino acids changing, and its increased antimicrobial effects against various bacterial and fungal strains [23]. Finally, they dealt with the human variants of Catestatin (Gly364Ser and Pro370Leu) and the evolutionary conservation of this peptide in mammals, pointing out the potential role of this peptide as a therapy for antibiotic-resistant superbugs and its role in innate immunity and the regulation of gut microbiota [23].…”
mentioning
confidence: 99%
“…The author reported the chemically modified isoform for this smaller peptide, with the total D-amino acids changing, and its increased antimicrobial effects against various bacterial and fungal strains [23]. Finally, they dealt with the human variants of Catestatin (Gly364Ser and Pro370Leu) and the evolutionary conservation of this peptide in mammals, pointing out the potential role of this peptide as a therapy for antibiotic-resistant superbugs and its role in innate immunity and the regulation of gut microbiota [23]. Also, Rizzetto and collaborators recapitulated the experience of their research group over 20 years in a narrative review describing the antibacterial and antifungal properties of several AMPs such as BMAP-28, Citropin 1.1, Temporin A, Distinctin, Magainin II, LL-37, Tritrpticin, Colistin, Distinctin, Magainin II, Cecropin A, and many others [24].…”
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