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

Caroline Dal Mas,Pedro I Da Silva Junior,Arnaldo Lopes Colombo,Eduardo B Oliveira,Jacques F Meis,Thaís Shimizu,Mirian A F Hayashi,Luana Rossato

doi:10.3390/biom9060205

Abstract

Invasive Candida 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 Candida auris 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 Candida 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 Candida isolates evaluated here showed resistance to amphotericin B and fluconazole, crotamine (40–80 µM) exhibited in vitro activity against most isolates tested. We suggest that this native polypeptide from the South American rattlesnake Crotalus durissus terrificus has potential as a structural model for the generation of a new class of antimicrobial compounds with the power to fight against multiresistant Candida spp.

Highlights

Infections caused by Candida spp. have progressively increased over the last decades, and this phenomenon is mainly associated with the increasing number of critically ill patients exposed to invasiveBiomolecules 2019, 9, 205; doi:10.3390/biom9060205 www.mdpi.com/journal/biomoleculesBiomolecules 2019, 9, 205 medical procedures, extensive use of broad-spectrum antibiotics, and treatment with immunosuppressants, which notably increase the risk in patients with neoplastic and/or degenerative diseases [1]
Candida auris infection has emerged as a serious problem in intensive care units (ICUs) of many countries, due to its reported emerging antifungal resistance, its easy transmission among patients in ICUs, because it is not identified by the most widely used phenotypic identification procedures employed in most clinical laboratories, and because it causes severe infection [3,4,5]
C. auris CBS 10913 reference strain was susceptible to all three antifungal drugs tested here

Summary

Introduction

Biomolecules 2019, 9, 205 medical procedures, extensive use of broad-spectrum antibiotics, and treatment with immunosuppressants, which notably increase the risk in patients with neoplastic and/or degenerative diseases [1]. All this had contributed to the promotion of Candida spp. infections as a public health concern in Europe, the Americas, and Asia [2,3,4]. Up to 90% of isolates are resistant to fluconazole (FLC), and 50% have reduced susceptibility to voriconazole, as demonstrated by elevated minimum inhibitory concentrations (MICs) [7]

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Discussion

Conclusion