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Antifungal activity of peptide MSI-1 against Cryptococcus neoformans infection in vitro and in murine cryptococcal meningoencephalitis.
- Source :
-
Peptides [Peptides] 2020 Aug; Vol. 130, pp. 170334. Date of Electronic Publication: 2020 Jun 03. - Publication Year :
- 2020
-
Abstract
- The development of novel antifungal agents with high efficacy, low drug tolerance and few side effects is urgent. MSI-1 (GIWKFLKKAKKFWK-NH <subscript>2</subscript> ), a cationic antimicrobial peptide, may be an attractive antifungal agent because of its structural characteristics, perfect stability against pH and high-temperature/salt, low toxicity towards mammalian cells and low potential for emergence of drug tolerance. In this study, the antifungal activity of MSI-1 in vitro and in a murine model of cryptococcal meningoencephalitis was evaluated. Zeta potential assay, flow cytometry, fluorescence microscope, transmission electron microscopy and microscale thermophoresis were performed to clarify the mechanisms underlying MSI-1 against C. neoformans. The results showed that MSI-1 exerted effective anti-cryptococcal activity in vitro, with MICs of 8-16 μg/mL and MFCs of 8-32 μg/mL, and in a C neoformans-infected mouse model, with significantly improved animal survival, decreased production of pro-inflammatory cytokines and alleviated lung injury, because the potent and rapid fungicidal activity of MSI-1 could effectively eliminate fungal counts in mouse organs. We confirmed that the positively charged peptide bound to C. neoformans by electrostatic attraction after interacting with glucuronoxylomannan (the primary component of C. neoformans capsule). Subsequently, MSI-1 increased the membrane fluidity of fungal cells and the cell membrane permeability, causing destabilized membrane integrity and leading to the final death of fungi. Collectively, MSI-1 possessed potent anti-cryptococcal activity via its notable membrane disruption effect and may be a potential candidate for use in antifungal infection induced by C. neoformans, especially azole-resistant cryptococcus.<br />Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest.<br /> (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Antifungal Agents metabolism
Antimicrobial Cationic Peptides chemistry
Antimicrobial Cationic Peptides pharmacology
Candida albicans drug effects
Cell Membrane drug effects
Cryptococcosis microbiology
Cytokines metabolism
Disease Models, Animal
Meningoencephalitis microbiology
Mice, Inbred BALB C
Microbial Sensitivity Tests
Peptides chemistry
Peptides metabolism
Polysaccharides metabolism
Antifungal Agents pharmacology
Cryptococcosis drug therapy
Cryptococcus neoformans drug effects
Meningoencephalitis drug therapy
Peptides pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-5169
- Volume :
- 130
- Database :
- MEDLINE
- Journal :
- Peptides
- Publication Type :
- Academic Journal
- Accession number :
- 32504765
- Full Text :
- https://doi.org/10.1016/j.peptides.2020.170334