4 research outputs found
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Selenium-silk microgels as antifungal and antibacterial agents â€
Acknowledgements: We would like to acknowledge the UKRI World Class Laboratories (WCL) fund for funding the Leica TCS SP8 inverted confocal microscope used for imaging in this paper. E. G. W. is funded by the Gates Cambridge Trust. Z. T. acknowledges funding from the Ron Thomson Research Fellowship in Alzheimer's Disease, Pembroke College Cambridge. A. K. J acknowledges funding from the Cambridge Trust, the EPSRC grant EP/L015978/1 for the Centre for Doctoral Training for Nanoscience and Nanotechnology (NanoDTC), Queens' College. T. P. J. K. acknowledges funding from the European Research Council under the European Unions Seventh Framework Programme (FP7/2007-2013) through the ERC grants PhysProt (agreement no. 337969), the Biotechnology and Biological Sciences Research Council (BBSRC), the Frances and Augustus Newman Foundation, and the Centre for Misfolding Diseases.Funder: FP7 Ideas: European Research Council; doi: https://doi.org/10.13039/100011199; Grant(s): UnassignedAntimicrobial resistance is a leading threat to global health. Alternative therapeutics to combat the rise in drug-resistant strains of bacteria and fungi are thus needed, but the development of new classes of small molecule therapeutics has remained challenging. Here, we explore an orthogonal approach and address this issue by synthesising micro-scale, protein colloidal particles that possess potent antimicrobial properties. We describe an approach for forming silk-based microgels that contain selenium nanoparticles embedded within the protein scaffold. We demonstrate that these materials have both antibacterial and antifungal properties while, crucially, also remaining highly biocompatible with mammalian cell lines. By combing the nanoparticles with silk, the protein microgel is able to fulfill two critical functions; it protects the mammalian cells from the cytotoxic effects of the bare nanoparticles, while simultaneously serving as a carrier for microbial eradication. Furthermore, since the antimicrobial activity originates from physical contact, bacteria and fungi are unlikely to develop resistance to our hybrid biomaterials, which remains a critical issue with current antibiotic and antifungal treatments. Therefore, taken together, these results provide the basis for innovative antimicrobial materials that can target drug-resistant microbial infections
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Selenium Silk Nanostructured Films with Antifungal and Antibacterial Activity.
Funder: Gates Cambridge TrustFunder: Biotechnology and Biological Sciences Research CouncilFunder: Centre for Misfolding Diseases, University of CambridgeFunder: Frances and Augustus Newman FoundationThe rapid emergence of drug-resistant bacteria and fungi poses a threat for healthcare worldwide. The development of novel effective small molecule therapeutic strategies in this space has remained challenging. Therefore, one orthogonal approach is to explore biomaterials with physical modes of action that have the potential to generate antimicrobial activity and, in some cases, even prevent antimicrobial resistance. Here, to this effect, we describe an approach for forming silk-based films that contain embedded selenium nanoparticles. We show that these materials exhibit both antibacterial and antifungal properties while crucially also remaining highly biocompatible and noncytotoxic toward mammalian cells. By incorporating the nanoparticles into silk films, the protein scaffold acts in a 2-fold manner; it protects the mammalian cells from the cytotoxic effects of the bare nanoparticles, while also providing a template for bacterial and fungal eradication. A range of hybrid inorganic/organic films were produced and an optimum concentration was found, which allowed for both high bacterial and fungal death while also exhibiting low mammalian cell cytotoxicity. Such films can thus pave the way for next-generation antimicrobial materials for applications such as wound healing and as agents against topical infections, with the added benefit that bacteria and fungi are unlikely to develop antimicrobial resistance to these hybrid materials
Recommended from our members
Selenium Silk Nanostructured Films with Antifungal and Antibacterial Activity.
Funder: FP7 Ideas: European Research Council; doi: 10.13039/100011199; Grant(s): 337969The rapid emergence of drug-resistant bacteria and fungi poses a threat for healthcare worldwide. The development of novel effective small molecule therapeutic strategies in this space has remained challenging. Therefore, one orthogonal approach is to explore biomaterials with physical modes of action that have the potential to generate antimicrobial activity and, in some cases, even prevent antimicrobial resistance. Here, to this effect, we describe an approach for forming silk-based films that contain embedded selenium nanoparticles. We show that these materials exhibit both antibacterial and antifungal properties while crucially also remaining highly biocompatible and noncytotoxic toward mammalian cells. By incorporating the nanoparticles into silk films, the protein scaffold acts in a 2-fold manner; it protects the mammalian cells from the cytotoxic effects of the bare nanoparticles, while also providing a template for bacterial and fungal eradication. A range of hybrid inorganic/organic films were produced and an optimum concentration was found, which allowed for both high bacterial and fungal death while also exhibiting low mammalian cell cytotoxicity. Such films can thus pave the way for next-generation antimicrobial materials for applications such as wound healing and as agents against topical infections, with the added benefit that bacteria and fungi are unlikely to develop antimicrobial resistance to these hybrid materials
Targeted peptide measurements in biology and medicine: best practices for mass spectrometry-based assay development using a fit-for-purpose approach.
Adoption of targeted mass spectrometry (MS) approaches such as multiple reaction monitoring (MRM) to study biological and biomedical questions is well underway in the proteomics community. Successful application depends on the ability to generate reliable assays that uniquely and confidently identify target peptides in a sample. Unfortunately, there is a wide range of criteria being applied to say that an assay has been successfully developed. There is no consensus on what criteria are acceptable and little understanding of the impact of variable criteria on the quality of the results generated. Publications describing targeted MS assays for peptides frequently do not contain sufficient information for readers to establish confidence that the tests work as intended or to be able to apply the tests described in their own labs. Guidance must be developed so that targeted MS assays with established performance can be made widely distributed and applied by many labs worldwide. To begin to address the problems and their solutions, a workshop was held at the National Institutes of Health with representatives from the multiple communities developing and employing targeted MS assays. Participants discussed the analytical goals of their experiments and the experimental evidence needed to establish that the assays they develop work as intended and are achieving the required levels of performance. Using this "fit-for-purpose" approach, the group defined three tiers of assays distinguished by their performance and extent of analytical characterization. Computational and statistical tools useful for the analysis of targeted MS results were described. Participants also detailed the information that authors need to provide in their manuscripts to enable reviewers and readers to clearly understand what procedures were performed and to evaluate the reliability of the peptide or protein quantification measurements reported. This paper presents a summary of the meeting and recommendations