Discovery of (meth)acrylate polymers that resist colonization by fungi associated with pathogenesis and biodeterioration

Vallières, Cindy; Hook, Andrew L.; He, Yinfeng; Crucitti, Valentina Cuzzucoli; Figueredo, Grazziela P.; Davies, Catheryn R.; Burroughs, Laurence; Winkler, David A.; Wildman, Ricky; Irvine, Derek J.; Alexander, Morgan R.; Avery, Simon V.

doi:10.1126/sciadv.aba6574

Cited by 34 publications

(36 citation statements)

References 44 publications

(53 reference statements)

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“…Alginate is a natural polymer that has been explored in antifungal and fungicide delivery systems, including with the carbamate thiram, due to its low toxicity, biodegradability, and low cost (Singh et al 2009a ; Singh et al 2009b ; Spadari et al 2017 ). Recently, polymeric materials that prevent fungal attachment and colonisation passively (i.e., without killing the organism), including by A. brasiliensis , have been discovered (Vallieres et al 2020a ). Incorporation of the combinations to those polymers could potentially offer added protection from harmful fungi.…”

Section: Discussionmentioning

confidence: 99%

Potentiated inhibition of Trichoderma virens and other environmental fungi by new biocide combinations

Vallières

Alexander

Avery

2021

Appl Microbiol Biotechnol

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Fungi cause diverse, serious socio-economic problems, including biodeterioration of valuable products and materials that spawns a biocides industry worth ~$11 billion globally. To help combat environmental fungi that commonly colonise material products, this study tested the hypothesis that combination of an approved fungicide with diverse agents approved by the FDA (Food and Drug Administration) could reveal potent combinatorial activities with promise for fungicidal applications. The strategy to use approved compounds lowers potential development risks for any effective combinations. A high-throughput assay of 1280 FDA-approved compounds was conducted to find those that potentiate the effect of iodopropynyl-butyl-carbamate (IPBC) on the growth of Trichoderma virens; IPBC is one of the two most widely used Biocidal Products Regulations–approved fungicides. From this library, 34 compounds in combination with IPBC strongly inhibited fungal growth. Low-cost compounds that gave the most effective growth inhibition were tested against other environmental fungi that are standard biomarkers for resistance of synthetic materials to fungal colonisation. Trifluoperazine (TFZ) in combination with IPBC enhanced growth inhibition of three of the five test fungi. The antifungal hexetidine (HEX) potentiated IPBC action against two of the test organisms. Testable hypotheses on the mechanisms of these combinatorial actions are discussed. Neither IPBC + TFZ nor IPBC + HEX exhibited a combinatorial effect against mammalian cells. These combinations retained strong fungal growth inhibition properties after incorporation to a polymer matrix (alginate) with potential for fungicide delivery. The study reveals the potential of such approved compounds for novel combinatorial applications in the control of fungal environmental opportunists. Key points • Search with an approved fungicide to find new fungicidal synergies in drug libraries. • New combinations inhibit growth of key environmental fungi on different matrices. • The approach enables a more rapid response to demand for new biocides.

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Section: Discussionmentioning

confidence: 99%

Potentiated inhibition of Trichoderma virens and other environmental fungi by new biocide combinations

Vallières

Alexander

Avery

2021

Appl Microbiol Biotechnol

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“…This work has uncovered a series of findings that point towards the reliable manufacturing of cellinstructive structures via IJ3DP. With the advances in high throughput technologies, materials libraries offering diverse functions are becoming widely available [21][22][23]37] . It is not trivial, however, to go from an idealized screening approach to materials usable within a manufacturing setting.…”

Section: Discussionmentioning

confidence: 99%

Inkjet based 3D Printing of bespoke medical devices that resist bacterial biofilm formation

Begines

Dubern

et al. 2020

Preprint

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AbstractWe demonstrate the formulation of advanced functional 3D printing inks that prevent the formation of bacterial biofilms in vivo. Starting from polymer libraries, we show that a biofilm resistant object can be 3D printed with the potential for shape and cell instructive function to be selected independently. When tested in vivo, the candidate materials not only resisted bacterial attachment but drove the recruitment of host defences in order to clear infection. To exemplify our approach, we manufacture a finger prosthetic and demonstrate that it resists biofilm formation – a cell instructive function that can prevent the development of infection during surgical implantation. More widely, cell instructive behaviours can be ‘dialled up’ from available libraries and may include in the future such diverse functions as the modulation of immune response and the direction of stem cell fate.

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“…Resistance to chemical fungicides is already well reported and several of the above strategies could also be undermined by emergence of resistance, as they impose a selective pressure on the fungi to adapt (or be inhibited/killed). Recently, a small group of (meth-)acrylate polymers were characterised which effectively block the attachment of B. cinerea spores to spray-coated leaf surfaces ( Vallieres et al. , 2020 ).…”

Section: Pre-harvest Fungal Controlmentioning

confidence: 99%

Evolving challenges and strategies for fungal control in the food supply chain

Davies

Wohlgemuth

Young

et al. 2021

Fungal Biology Reviews

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Fungi that spoil foods or infect crops can have major socioeconomic impacts, posing threats to food security. The strategies needed to manage these fungi are evolving, given the growing incidence of fungicide resistance, tightening regulations of chemicals use and market trends imposing new food-preservation challenges. For example, alternative methods for crop protection such as RNA-based fungicides, biocontrol, or stimulation of natural plant defences may lessen concerns like environmental toxicity of chemical fungicides. There is renewed focus on natural product preservatives and fungicides, which can bypass regulations for ‘clean label’ food products. These require investment to find effective, safe activities within complex mixtures such as plant extracts. Alternatively, physical measures may be one key for fungal control, such as polymer materials which passively resist attachment and colonization by fungi. Reducing or replacing traditional chlorine treatments ( e.g. of post-harvest produce) is desirable to limit formation of disinfection by-products. In addition, the current growth in lower sugar food products can alter metabolic routing of carbon utilization in spoilage yeasts, with implications for efficacy of food preservatives acting via metabolism. The use of preservative or fungicide combinations, while involving more than one chemical, can reduce total chemicals usage where these act synergistically. Such approaches might also help target different subpopulations within heteroresistant fungal populations. These approaches are discussed in the context of current challenges for food preservation, focussing on pre-harvest fungal control, fresh produce and stored food preservation. Several strategies show growing potential for mitigating or reversing the risks posed by fungi in the food supply chain.

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Discovery of (meth)acrylate polymers that resist colonization by fungi associated with pathogenesis and biodeterioration

Cited by 34 publications

References 44 publications

Potentiated inhibition of Trichoderma virens and other environmental fungi by new biocide combinations

Potentiated inhibition of Trichoderma virens and other environmental fungi by new biocide combinations

Inkjet based 3D Printing of bespoke medical devices that resist bacterial biofilm formation

Evolving challenges and strategies for fungal control in the food supply chain

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