Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Giving a Hand: Synthetic Peptides Boost the Antifungal Activity of Itraconazole against Cryptococcus Neoformans

Tawanny K. B. Aguiar
ORCID logo ,
Ricardo M. Feitosa
,
Nilton A. S. Neto
,
Ellen A. Malveira
,
Francisco I. R. Gomes
,
Ana C. M. Costa
,
Cleverson D. T. Freitas
ORCID logo ,
Felipe Pantoja Mesquita
,
Pedro Filho Noronha Souza
* ORCID logo
Version 1 : Received: 22 December 2022 / Approved: 26 December 2022 / Online: 26 December 2022 (03:44:06 CET)

A peer-reviewed article of this Preprint also exists.

Aguiar, T.K.B.; Feitosa, R.M.; Neto, N.A.S.; Malveira, E.A.; Gomes, F.I.R.; Costa, A.C.M.; Freitas, C.D.T.; Mesquita, F.P.; Souza, P.F.N. Giving a Hand: Synthetic Peptides Boost the Antifungal Activity of Itraconazole against Cryptococcus neoformans. Antibiotics 2023, 12, 256. Aguiar, T.K.B.; Feitosa, R.M.; Neto, N.A.S.; Malveira, E.A.; Gomes, F.I.R.; Costa, A.C.M.; Freitas, C.D.T.; Mesquita, F.P.; Souza, P.F.N. Giving a Hand: Synthetic Peptides Boost the Antifungal Activity of Itraconazole against Cryptococcus neoformans. Antibiotics 2023, 12, 256.

Abstract

Cryptococcus neoformans is a multidrug-resistant human pathogenic yeast responsible for infections in immunocompromised patients. Here, Itraconazole (ITR), a commercial antifungal drug with low effectiveness against C. neoformans, was combined with different synthetic peptides Mo-CBP3-PepII, RcAlb-PepII, RcAlb-PepIII, PepGAT, and PepKAA. The mechanisms of action responsible for the synergistic effect were evaluated for the best combinations by Fluorescence Microscopy (FM). The synthetic peptides enhanced the activity of ITR by 10-fold against C. neoformans. Our results demonstrated that the combinations could induce pore formation in the membrane and overaccumulation of ROS on C. neoformans cells. Our findings indicate that our peptides successfully potentialize the activity of ITR by reducing it by 10-fold to reach antifungal activity against C. neoformans. Therefore, synthetic peptides are potential molecules to act as co-adjuvant agents in treating Cryptococcal infections.

Keywords

azole drugs; cryptococcal meningitis; resistance; synergism; synthetic antifungal peptides

Subject

Biology and Life Sciences, Immunology and Microbiology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Download PDF Download Supplementary

Comments (0)

We encourage comments and feedback from a broad range of readers. See criteria for comments and our Diversity statement.

Leave a public comment
Send a private comment to the author(s)
* All users must log in before leaving a comment
Views 0
Downloads 0
Comments 0
Metrics 0
Get PDF Supplementary Files Cite Share 0
Bookmark BibSonomy Mendeley Reddit Delicious
×
Alerts
Notify me about updates to this article or when a peer-reviewed version is published.
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here.