The antimicrobial peptide MK58911-NH2 acts on planktonic, biofilm, and intramacrophage cells of cryptococcus neoformans

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dc.contributor.authorde Lacorte Singulani, Junya [UNESP]
dc.contributor.authorOliveira, Lariane Teodoro [UNESP]
dc.contributor.authorRamos, Marina Dorisse [UNESP]
dc.contributor.authorFregonezi, Nathália Ferreira [UNESP]
dc.contributor.authorGomes, Paulo César [UNESP]
dc.contributor.authorGaleane, Mariana Cristina [UNESP]
dc.contributor.authorPalma, Mario Sergio [UNESP]
dc.contributor.authorFusco Almeida, Ana Marisa [UNESP]
dc.contributor.authorMendes Giannini, Maria José Soares [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (UNESP)
dc.date.accessioned2022-04-29T08:36:37Z
dc.date.available2022-04-29T08:36:37Z
dc.date.issued2021-12-01
dc.description.abstractCryptococcosis 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.en
dc.description.affiliationDepartment of Clinical Analysis School of Pharmaceutical Sciences São Paulo State University-UNESP
dc.description.affiliationDepartment of Basic and Applied Biology Institute of Biosciences São Paulo State University-UNESP
dc.description.affiliationUnespDepartment of Clinical Analysis School of Pharmaceutical Sciences São Paulo State University-UNESP
dc.description.affiliationUnespDepartment of Basic and Applied Biology Institute of Biosciences São Paulo State University-UNESP
dc.identifierhttp://dx.doi.org/10.1128/AAC.00904-21
dc.identifier.citationAntimicrobial Agents and Chemotherapy, v. 65, n. 12, 2021.
dc.identifier.doi10.1128/AAC.00904-21
dc.identifier.issn1098-6596
dc.identifier.issn0066-4804
dc.identifier.scopus2-s2.0-85119352942
dc.identifier.urihttp://hdl.handle.net/11449/229909
dc.language.isoeng
dc.relation.ispartofAntimicrobial Agents and Chemotherapy
dc.sourceScopus
dc.subjectAntifungal activity
dc.subjectAntifungal agents
dc.subjectAntimicrobial peptide
dc.subjectBiofilm
dc.subjectCryptococcosis
dc.subjectCryptococcus neoformans
dc.subjectIntramacrophage activity
dc.subjectMechanisms of action
dc.subjectNonconventional animal models
dc.subjectSystemic fungi
dc.subjectSystemic mycoses
dc.titleThe antimicrobial peptide MK58911-NH2 acts on planktonic, biofilm, and intramacrophage cells of cryptococcus neoformansen
dc.typeArtigo

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