PUBLICATION
The antimicrobial peptide MK58911-NH2 acts on planktonic, biofilm and intramacrophage cells of Cryptococcus neoformans
- Authors
- Singulani, J.L., Oliveira, L.T., Ramos, M.D., Fregonezi, N.F., Gomes, P.C., Galeane, M.C., Palma, M.S., Fusco Almeida, A.M., Mendes Giannini, M.J.S.
- ID
- ZDB-PUB-210914-12
- Date
- 2021
- Source
- Antimicrobial Agents and Chemotherapy 65(12): e0090421 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Antifungal Agents/pharmacology*
- Antimicrobial Peptides/pharmacology*
- Biofilms
- Cryptococcosis/drug therapy
- Cryptococcus neoformans*/drug effects
- Humans
- Macrophages/microbiology
- Microbial Sensitivity Tests
- Zebrafish
- PubMed
- 34516241 Full text @ Antimicrob. Agents Chemother.
Citation
Singulani, J.L., Oliveira, L.T., Ramos, M.D., Fregonezi, N.F., Gomes, P.C., Galeane, M.C., Palma, M.S., Fusco Almeida, A.M., Mendes Giannini, M.J.S. (2021) The antimicrobial peptide MK58911-NH2 acts on planktonic, biofilm and intramacrophage cells of Cryptococcus neoformans. Antimicrobial Agents and Chemotherapy. 65(12):e0090421.
Abstract
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 cause unavoidable toxicity issues to 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 wasps peptide toxins, MK58911-NH2, on Cryptococcus neoformans. It was 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 relation 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 cell wall - binding dye calcofluor or capsule- binding dye 18b7 antibody-FITC of C. neoformans, but rather reduced the number and size of fungal cells. This activity reduced the fungal burden of C. neoformans both in macrophages and in zebrafish embryos as well as within biofilms. Three fragments of the MK58911-NH2 peptide showed no activity against Cryptococcus or toxicity in lung cells. The derivative peptide MH58911-NH2, in which the lysine residues of MK58911-NH2 were replaced by histidine, reduced the activity against extracellular and intracellular C. neoformans. On the other hand, it was active against biofilm, and reducing toxicity. In summary, the results showed that peptide MK58911-NH2 could be a promising agent against cryptococcosis. The work also opens a perspective for the verification of the antifungal activity of other derivatives.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping