The Antimicrobial Peptide MK58911-NH 2 Acts on Planktonic, Biofilm, and Intramacrophage Cells of Cryptococcus neoformans
| Autor: | Nathália Ferreira Fregonezi, Junya de Lacorte Singulani, Mario Sergio Palma, Marina Dorisse Ramos, Ana Marisa Fusco Almeida, Paulo César Gomes, Maria José Soares Mendes Giannini, Mariana Cristina Galeane, Lariane Teodoro Oliveira |
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| Přispěvatelé: | Universidade Estadual Paulista (UNESP) |
| Rok vydání: | 2021 |
| Předmět: |
Antifungal Agents
antimicrobial peptide cryptococcosis Antimicrobial peptides Cryptococcus Peptide Microbial Sensitivity Tests Nonconventional animal models Intramacrophage activity biofilm Microbiology Flucytosine systemic fungi Mechanisms of action systemic mycoses medicine Animals Humans Experimental Therapeutics Pharmacology (medical) Antifungal activity Antifungal agents Zebrafish Pharmacology chemistry.chemical_classification Cryptococcus neoformans biology Macrophages Biofilm antifungal activity Systemic mycoses Cryptococcosis nonconventional animal models biology.organism_classification Antimicrobial medicine.disease mechanisms of action Infectious Diseases chemistry Systemic fungi Biofilms intramacrophage activity Antimicrobial peptide Antimicrobial Peptides medicine.drug |
| Zdroj: | Scopus Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP Antimicrobial Agents and Chemotherapy |
| ISSN: | 1098-6596 0066-4804 |
| DOI: | 10.1128/aac.00904-21 |
| Popis: | Made available in DSpace on 2022-04-29T08:36:37Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-12-01 Cryptococcosis is associated with high rates of morbidity and mortality, especially in AIDS patients. Its treatment is carried out by combining amphotericin B and azoles or flucytosine, which causes unavoidable toxicity issues in the host. Thus, the urgency in obtaining new antifungals drives the search for antimicrobial peptides (AMPs). This study aimed to extend the understanding of the mechanism of action of an AMP analog from wasp peptide toxins, MK58911-NH2, on Cryptococcus neoformans. We also evaluated if MK58911-NH2 can act on cryptococcal cells in macrophages, biofilms, and an immersion zebrafish model of infection. Finally, we investigated the structure-antifungal action and the toxicity relationship of MK58911-NH2 fragments and a derivative of this peptide (MH58911-NH2). The results demonstrated that MK58911-NH2 did not alter the fluorescence intensity of the cell wall-binding dye calcofluor white or the capsule-binding dye 18b7 antibody-fluorescein isothiocyanate (FITC) in C. neoformans but rather reduced the number and size of fungal cells. This activity reduced the fungal burden of C. neoformans in both macrophages and zebrafish embryos as well as within biofilms. Three fragments of the MK58911-NH2 peptide showed no activity against Cryptococcus and not toxicity in lung cells. The derivative peptide MH58911-NH2, in which the lysine residues of MK58911-NH2 were replaced by histidines, reduced the activity against extracellular and intracellular C. neoformans. On the other hand, it was active against biofilms and showed reduced toxicity. In summary, these results showed that peptide MK58911-NH2 could be a promising agent against cryptococcosis. This work also opens a perspective for the verification of the antifungal activity of other derivatives. Department of Clinical Analysis School of Pharmaceutical Sciences São Paulo State University-UNESP Department of Basic and Applied Biology Institute of Biosciences São Paulo State University-UNESP Department of Clinical Analysis School of Pharmaceutical Sciences São Paulo State University-UNESP Department of Basic and Applied Biology Institute of Biosciences São Paulo State University-UNESP |
| Databáze: | OpenAIRE |
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