An Immunomodulatory Peptide Confers Protection in an Experimental Candidemia Murine Model

Freitas, Camila Guimarães de; Lima, Stella M. F.; Freire, Mirna S.; Cantuária, Ana Paula de Castro; Oliveira-Júnior, Nelson G.; Santos, Tatiane S.; Folha, Jéssica S.; Ribeiro, Suzana Meira; Dias, Simoni Campos; Rezende, Taia Maria Berto; Albuquerque, Patrícia; Nicola, André Moraes; Fuente-Núñez, César de la; Hancock, Robert E. W.; Franco, Octávio L.; Felipe, Maria Sueli Soares

doi:10.1128/aac.02518-16

Cited by 24 publications

(19 citation statements)

References 46 publications

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“…Unlike conventional antibiotics, these compounds have been shown to interfere with secondary messenger molecules such as ppGpp [15] and can have multiple mechanisms of action, which may decrease the possibility of resistance development in future therapies. More recently there is evidence that such peptides can also target fungal biofilms [20], but the basis for this activity is currently unknown.…”

Section: Mechanisms Of Anti-biofilm Peptides: Not Only Membrane Disrumentioning

confidence: 99%

Design and Assessment of Anti-Biofilm Peptides: Steps Toward Clinical Application

Dostert¹,

Belanger²,

Hancock³

2018

J Innate Immun

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Highly antibiotic resistant, microbial communities, referred to as biofilms, cause various life-threatening infections in humans. At least two-thirds of all clinical infections are biofilm associated, and antibiotic therapy regularly fails to cure patients. Anti-biofilm peptides represent a promising approach to treat these infections by targeting biofilm-specific characteristics such as highly conserved regulatory mechanisms. They are being considered for clinical application and we discuss here key factors in discovery, design, and application, particularly the implementation of host-mimicking conditions, that are required to enable the successful advancement of potent anti-biofilm peptides from the bench to the clinic.

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Section: Mechanisms Of Anti-biofilm Peptides: Not Only Membrane Disrumentioning

confidence: 99%

Design and Assessment of Anti-Biofilm Peptides: Steps Toward Clinical Application

Dostert¹,

Belanger²,

Hancock³

2018

J Innate Immun

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“…Nevertheless, whether the regenerative effect of IDR‐1018 is only an indirect product of its influence over immune cells or if it is a direct consequence of its effects over skin cells (i.e., hFibs and Kcs) had never been shown in the absence of immune cells and infection or by using human primary cells. Our group previously investigated IDR‐1018 by analyzing its role against murine experimental candidemia (Freitas et al, ). In the present work, we focused on a more translational evaluation of the regenerative potential of IDR‐1018 in a human scenario.…”

Section: Discussionmentioning

confidence: 99%

IDR‐1018 induces cell proliferation, migration, and reparative gene expression in 2D culture and 3D human skin equivalents

Alencar‐Silva

Zonari²,

Foyt³

et al. 2019

J Tissue Eng Regen Med

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Skin lesions are associated with functional/cosmetic problems for those afflicted. Scarless regeneration is a challenge, not limited to the skin, and focus of active investigation. Recently, the host defense peptide innate defense regulatory peptide 1018 (IDR‐1018) has shown exciting regenerative properties. Nevertheless, literature regarding IDR‐1018 regenerative potential is scarce and limited to animal models. Here, we evaluated the regenerative potential of IDR‐1018 using human 2D and 3D human skin equivalents. First, we investigated IDR‐1018 using human cells found in skin—primary fibroblasts, primary keratinocytes, and the MeWo melanocytes cell line. IDR‐1018 promoted cell proliferation and expression of marker of proliferation Ki‐67, matrix metalloproteinase 1, and hyaluronan synthase 2 by fibroblasts. In keratinocytes, a drastic increase in expression was observed for Ki‐67, matrix metalloproteinase 1, C‐X‐C motif chemokine receptor type 4, C‐X‐C motif chemokine receptor type 7, fibroblast growth factor 2, hyaluronan synthase 2, vascular endothelial growth factor, and elastin, reflecting an intense stimulation of these cells. In melanocytes, increased migration and proliferation were observed following IDR‐1018 treatment. The capacity of IDR‐1018 to promote dermal contraction was verified using a dermal model. Finally, using a 3D human skin equivalent lesion model, we revealed that the regenerative potential of IDR1018, previously tested in mice and pigs, is valid for human skin tissue. Lesions closed faster in IDR‐1018‐treated samples, and the gene expression signature observed in 2D was reproduced in the 3D human skin equivalents. Overall, the present data show the regenerative potential of IDR‐1018 in an experimental system comprising human cells, underscoring the potential application for clinical investigation.

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“…2,6-Bis[(E)-(4-pyridyl)methylidene]cyclohexanone, an antiparasitic compound, was also found to exhibit antifungal properties including the inhibition of Candida filamentation, crucial in biofilm formation (de Sá et al, 2018). Antifungal peptide derivatives of H-5 are also being explored (Sultan et al, 2019), and other host defense peptides such as innate defense regulator 1018 and porcine cathelicidins have recently been shown to possess antifungal and antibiofilm properties against Candida (Lyu et al, 2016;Freitas et al, 2017). These compounds are potential candidates for incorporation into antifungal biomaterials.…”

Section: Preventing Candida Biofilms Using Surface Modification With mentioning

confidence: 99%

Advances in Biomaterials for the Prevention and Disruption of Candida Biofilms

Vera‐González

Shukla

2020

Front. Microbiol.

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Candida species can readily colonize a multitude of indwelling devices, leading to biofilm formation. These three-dimensional, surface-associated Candida communities employ a multitude of sophisticated mechanisms to evade treatment, leading to persistent and recurrent infections with high mortality rates. Further complicating matters, the current arsenal of antifungal therapeutics that are effective against biofilms is extremely limited. Antifungal biomaterials are gaining interest as an effective strategy for combating Candida biofilm infections. In this review, we explore biomaterials developed to prevent Candida biofilm formation and those that treat existing biofilms. Surface functionalization of devices employing clinically utilized antifungals, other antifungal molecules, and antifungal polymers has been extremely effective at preventing fungi attachment, which is the first step of biofilm formation. Several mechanisms can lead to this attachment inhibition, including contact killing and release-based killing of surrounding planktonic cells. Eliminating mature biofilms is arguably much more difficult than prevention. Nanoparticles have shown the most promise in disrupting existing biofilms, with the potential to penetrate the dense fungal biofilm matrix and locally target fungal cells. We will describe recent advances in both surface functionalization and nanoparticle therapeutics for the treatment of Candida biofilms.

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An Immunomodulatory Peptide Confers Protection in an Experimental Candidemia Murine Model

Cited by 24 publications

References 46 publications

Design and Assessment of Anti-Biofilm Peptides: Steps Toward Clinical Application

Design and Assessment of Anti-Biofilm Peptides: Steps Toward Clinical Application

IDR‐1018 induces cell proliferation, migration, and reparative gene expression in 2D culture and 3D human skin equivalents

Advances in Biomaterials for the Prevention and Disruption of Candida Biofilms

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