Effects of the Natural Peptide Crotamine from a South American Rattlesnake on <i>Candida auris</i>, an Emergent Multidrug Antifungal Resistant Human Pathogen

Invasive <i>Candida</i> infections are an important growing medical concern and treatment options are limited to a few antifungal drug classes, with limited efficacies depending on the infecting organism. In this scenario, invasive infections caused by multiresistant <i>Candida aur...

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Main Authors: Caroline Dal Mas, Luana Rossato, Thaís Shimizu, Eduardo B. Oliveira, Pedro I. da Silva Junior, Jacques F. Meis, Arnaldo Lopes Colombo, Mirian A. F. Hayashi
Format: Article
Language:English
Published: MDPI AG 2019-05-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/9/6/205
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spelling doaj-8782926f4880455b98fcfb0679dd6eb82020-11-25T02:10:47ZengMDPI AGBiomolecules2218-273X2019-05-019620510.3390/biom9060205biom9060205Effects of the Natural Peptide Crotamine from a South American Rattlesnake on <i>Candida auris</i>, an Emergent Multidrug Antifungal Resistant Human PathogenCaroline Dal Mas0Luana Rossato1Thaís Shimizu2Eduardo B. Oliveira3Pedro I. da Silva Junior4Jacques F. Meis5Arnaldo Lopes Colombo6Mirian A. F. Hayashi7Departamento de Farmacologia, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), São Paulo SP 04038-032, BrazilDepartamento de Medicina, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), São Paulo SP 04038-032, BrazilDepartamento de Farmacologia, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), São Paulo SP 04038-032, BrazilDepartamento de Bioquímica e Imunologia, Universidade de São Paulo (USP-RP), Ribeirão Preto SP 14049-900, BrazilSpecial Laboratory for Applied Toxinology (LETA), Center of Toxins, Immune-Response and Cell Signaling (CeTICS), Butantan Institute, São Paulo SP 05503-900, BrazilCenter of Expertise in Mycology Radboudumc/CWZ, Department of Medical Microbiology and Infectious Diseases, Canisius-Wilhelmina Hospital (CWZ), 6532 Nijmegen, The NetherlandsDepartamento de Medicina, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), São Paulo SP 04038-032, BrazilDepartamento de Farmacologia, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), São Paulo SP 04038-032, BrazilInvasive <i>Candida</i> infections are an important growing medical concern and treatment options are limited to a few antifungal drug classes, with limited efficacies depending on the infecting organism. In this scenario, invasive infections caused by multiresistant <i>Candida auris</i> are emerging in several places around the world as important healthcare-associated infections. As antimicrobial peptides (AMPs) exert their activities primarily through mechanisms involving membrane disruption, they have a lower chance of inducing drug resistance than general chemical antimicrobials. Interestingly, we previously described the potent candicidal effect of a rattlesnake AMP, crotamine, against standard and treatment-resistant clinical isolates, with no hemolytic activity. We evaluated the antifungal susceptibility of several <i>Candida</i> spp. strains cultured from different patients by using the Clinical and Laboratory Standards Institute (CLSI) microdilution assay, and the antifungal activity of native crotamine was evaluated by a microbial growth inhibition microdilution assay. Although all <i>Candida</i> isolates evaluated here showed resistance to amphotericin B and fluconazole, crotamine (40&#8722;80 &#181;M) exhibited in vitro activity against most isolates tested. We suggest that this native polypeptide from the South American rattlesnake <i>Crotalus durissus terrificus</i> has potential as a structural model for the generation of a new class of antimicrobial compounds with the power to fight against multiresistant <i>Candida</i> spp.https://www.mdpi.com/2218-273X/9/6/205rattlesnake venom toxincrotamineantimicrobial peptidemultiresistant strainfungus<i>Candida</i> spp.
collection DOAJ
language English
format Article
sources DOAJ
author Caroline Dal Mas
Luana Rossato
Thaís Shimizu
Eduardo B. Oliveira
Pedro I. da Silva Junior
Jacques F. Meis
Arnaldo Lopes Colombo
Mirian A. F. Hayashi
spellingShingle Caroline Dal Mas
Luana Rossato
Thaís Shimizu
Eduardo B. Oliveira
Pedro I. da Silva Junior
Jacques F. Meis
Arnaldo Lopes Colombo
Mirian A. F. Hayashi
Effects of the Natural Peptide Crotamine from a South American Rattlesnake on <i>Candida auris</i>, an Emergent Multidrug Antifungal Resistant Human Pathogen
Biomolecules
rattlesnake venom toxin
crotamine
antimicrobial peptide
multiresistant strain
fungus
<i>Candida</i> spp.
author_facet Caroline Dal Mas
Luana Rossato
Thaís Shimizu
Eduardo B. Oliveira
Pedro I. da Silva Junior
Jacques F. Meis
Arnaldo Lopes Colombo
Mirian A. F. Hayashi
author_sort Caroline Dal Mas
title Effects of the Natural Peptide Crotamine from a South American Rattlesnake on <i>Candida auris</i>, an Emergent Multidrug Antifungal Resistant Human Pathogen
title_short Effects of the Natural Peptide Crotamine from a South American Rattlesnake on <i>Candida auris</i>, an Emergent Multidrug Antifungal Resistant Human Pathogen
title_full Effects of the Natural Peptide Crotamine from a South American Rattlesnake on <i>Candida auris</i>, an Emergent Multidrug Antifungal Resistant Human Pathogen
title_fullStr Effects of the Natural Peptide Crotamine from a South American Rattlesnake on <i>Candida auris</i>, an Emergent Multidrug Antifungal Resistant Human Pathogen
title_full_unstemmed Effects of the Natural Peptide Crotamine from a South American Rattlesnake on <i>Candida auris</i>, an Emergent Multidrug Antifungal Resistant Human Pathogen
title_sort effects of the natural peptide crotamine from a south american rattlesnake on <i>candida auris</i>, an emergent multidrug antifungal resistant human pathogen
publisher MDPI AG
series Biomolecules
issn 2218-273X
publishDate 2019-05-01
description Invasive <i>Candida</i> infections are an important growing medical concern and treatment options are limited to a few antifungal drug classes, with limited efficacies depending on the infecting organism. In this scenario, invasive infections caused by multiresistant <i>Candida auris</i> are emerging in several places around the world as important healthcare-associated infections. As antimicrobial peptides (AMPs) exert their activities primarily through mechanisms involving membrane disruption, they have a lower chance of inducing drug resistance than general chemical antimicrobials. Interestingly, we previously described the potent candicidal effect of a rattlesnake AMP, crotamine, against standard and treatment-resistant clinical isolates, with no hemolytic activity. We evaluated the antifungal susceptibility of several <i>Candida</i> spp. strains cultured from different patients by using the Clinical and Laboratory Standards Institute (CLSI) microdilution assay, and the antifungal activity of native crotamine was evaluated by a microbial growth inhibition microdilution assay. Although all <i>Candida</i> isolates evaluated here showed resistance to amphotericin B and fluconazole, crotamine (40&#8722;80 &#181;M) exhibited in vitro activity against most isolates tested. We suggest that this native polypeptide from the South American rattlesnake <i>Crotalus durissus terrificus</i> has potential as a structural model for the generation of a new class of antimicrobial compounds with the power to fight against multiresistant <i>Candida</i> spp.
topic rattlesnake venom toxin
crotamine
antimicrobial peptide
multiresistant strain
fungus
<i>Candida</i> spp.
url https://www.mdpi.com/2218-273X/9/6/205
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