Antifungal Potential of Synthetic Peptides against <i>Cryptococcus neoformans</i>: Mechanism of Action Studies Reveal Synthetic Peptides Induce Membrane–Pore Formation, DNA Degradation, and Apoptosis
Tawanny K. B. Aguiar,
Nilton A. S. Neto,
Cleverson D. T. Freitas,
Ayrles F. B. Silva,
Leandro P. Bezerra,
Ellen A. Malveira,
Levi A. C. Branco,
Felipe P. Mesquita,
Gustavo H. Goldman,
Luciana M. R. Alencar,
Jose T. A. Oliveira,
Ralph Santos-Oliveira,
Pedro F. N. Souza
Affiliations
Tawanny K. B. Aguiar
Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza 60451-970, CE, Brazil
Nilton A. S. Neto
Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza 60451-970, CE, Brazil
Cleverson D. T. Freitas
Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza 60451-970, CE, Brazil
Ayrles F. B. Silva
Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza 60451-970, CE, Brazil
Leandro P. Bezerra
Department of Fisheries Engineering, Federal University of Ceará, Fortaleza 60455-970, CE, Brazil
Ellen A. Malveira
Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza 60451-970, CE, Brazil
Levi A. C. Branco
Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza 60451-970, CE, Brazil
Felipe P. Mesquita
Drug Research and Development Center, Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza 60430-275, CE, Brazil
Gustavo H. Goldman
Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, São Paulo 14040-903, SP, Brazil
Luciana M. R. Alencar
Department of Physics, Laboratory of Biophysics and Nanosystems, Federal University of Maranhão, São Luís 65080-805, MA, Brazil
Jose T. A. Oliveira
Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza 60451-970, CE, Brazil
Ralph Santos-Oliveira
Laboratory of Nanoradiopharmaceuticals and Radiopharmacy, Zona Oeste State University, Rio de Janeiro 23070-200, RJ, Brazil
Pedro F. N. Souza
Department of Biochemistry and Molecular Biology, Federal University of Ceará, Fortaleza 60451-970, CE, Brazil
Cryptococcus neoformans is a human-pathogenic yeast responsible for pneumonia and meningitis, mainly in patients immunocompromised. Infections caused by C. neoformans are a global health concern. Synthetic antimicrobial peptides (SAMPs) have emerged as alternative molecules to cope with fungal infections, including C. neoformans. Here, eight SAMPs were tested regarding their antifungal potential against C. neoformans and had their mechanisms of action elucidated by fluorescence and scanning electron microscopies. Five SAMPs showed an inhibitory effect (MIC50) on C. neoformans growth at low concentrations. Fluorescence microscope (FM) revealed that SAMPs induced 6-kDa pores in the C. neoformans membrane. Inhibitory assays in the presence of ergosterol revealed that some peptides lost their activity, suggesting interaction with it. Furthermore, FM analysis revealed that SAMPs induced caspase 3/7-mediated apoptosis and DNA degradation in C. neoformans cells. Scanning Electron Microscopy (SEM) analysis revealed that peptides induced many morphological alterations such as cell membrane, wall damage, and loss of internal content on C. neoformans cells. Our results strongly suggest synthetic peptides are potential alternative molecules to control C. neoformans growth and treat the cryptococcal infection.
