Crotamine: Function Diversity and Potential Applications

Marinovic, Marcelo Paradiso; Mas, Caroline Dal; Monte, Gabriela Guilherme; Felix, Daniel A.; Campeiro, Joana D’Arc; Hayashi, Mirian A. F.

doi:10.1007/978-94-007-6648-8_28-1

Cited by 3 publications

(1 citation statement)

References 81 publications

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“…Crotamine is a well-characterized polypeptide with multiple biological activities [37], including the in vitro activity against a selected panel of Candida species [23]. Crotamine is also a recognized member of the antimicrobial peptide (AMPs) class whose members are efficient in killing most microbes, and for which the development of resistance is rare, mainly due to the characteristic mechanism(s) of action based on the rapid interaction with and disruption of lipid cell membranes [15,19,38].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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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.

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Section: Discussionmentioning

confidence: 99%

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

et al. 2019

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Crotamine induces browning of adipose tissue and increases energy expenditure in mice

Marinovic

Campeiro

Lima

et al. 2018

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Crotamine, originally isolated from rattlesnake venom, has been extensively studied due to its pleiotropic biological properties, and special attention has been paid to its antitumor activity. However, long-term treatment with crotamine was accompanied by a reduction in animal body weight gain and by increases in glucose tolerance. As cancer is commonly associated with cachexia, to preclude the possible cancer cachexia-like effect of crotamine, herein this polypeptide was administered in healthy wild-type C57/BL6 mice by the oral route daily, for 21 days. Reduced body weight gain, in addition to decreased white adipose tissue (WAT) and increased brown adipose tissue (BAT) mass were observed in healthy animals in the absence of tumor. In addition, we observed improved glucose tolerance and increased insulin sensitivity, accompanied by a reduction of plasma lipid levels and decreased levels of biomarkers of liver damage and kidney disfunctions. Importantly, long-term treatment with crotamine increased the basal metabolic rate in vivo, which was consistent with the increased expression of thermogenic markers in BAT and WAT. Interestingly, cultured brown adipocyte cells induced to differentiation in the presence of crotamine also showed increases in some of these markers and in lipid droplets number and size, indicating increased brown adipocyte maturation.

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Long term safety of targeted internalization of cell penetrating peptide crotamine into renal proximal tubular epithelial cells in vivo

Campeiro

Dam

Monte

et al. 2019

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Activated proximal tubular epithelial cells (PTECs) play a crucial role in progressive tubulo-interstitial fibrosis in native and transplanted kidneys. Targeting PTECs by non-viral delivery vectors might be useful to influence the expression of important genes and/or proteins in order to slow down renal function loss. However, no clinical therapies that specifically target PTECs are available at present. We earlier showed that a cationic cell penetrating peptide isolated from South American rattlesnake venom, named crotamine, recognizes cell surface heparan sulfate proteoglycans and accumulates in cells. In healthy mice, crotamine accumulates mainly in kidneys after intraperitoneal ( ip ) injection. Herein we demonstrate for the first time, the overall safety of acute or long-term treatment with daily ip administrated crotamine for kidneys functions. Accumulation of ip injected crotamine in the kidney brush border zone of PTECs, and its presence inside these cells were observed. In addition, significant lower in vitro crotamine binding, uptake and reporter gene transport and expression could be observed in syndecan-1 deficient HK-2 PTECs compared to wild-type cells, indicating that the absence of syndecan-1 impairs crotamine uptake into PTECs. Taken together, our present data show the safety of in vivo long-term treatment with crotamine, and its preferential uptake into PTECs, which are especially rich in HSPGs such as syndecan-1. In addition to the demonstrated in vitro gene delivery mediated by crotamine in HK-2 cells, the potential applicability of crotamine as prototypic non-viral (gene) delivery nanocarrier to modulate PTEC gene and/or protein expression was confirmed.

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Crotamine: Function Diversity and Potential Applications

Cited by 3 publications

References 81 publications

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

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

Crotamine induces browning of adipose tissue and increases energy expenditure in mice

Long term safety of targeted internalization of cell penetrating peptide crotamine into renal proximal tubular epithelial cells in vivo

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