A strategy to overcome multispecies vascular catheter-related infections

Funding Information: The authors thank Fundação para a Ciência e Tecnologia (FCT) Portugal, for the financial support under the Project PTDC/BTM-SAL/29335/2017 . Portugal 2020 for the Portuguese Mass Spectrometry Network (Rede Nacional de Espectrometria de Massa RNEM ) is also acknowledged. The authors also acknowledge the Designer Nuno Monge for the artwork, Isabel Dias Nogueira (Microlab, Instituto Superior Técnico, Lisbon University) for the technical assistance with the SEM analysis, Andreia Bento for the assistance with the UHPLC-MS equipment (iMed.Ulisboa) and Professor Maria José Ferreira (FFULisboa) for allowing the use of the automatic flash chromatography equipment. Funding Information: The authors thank Fundação para a Ciência e Tecnologia (FCT) Portugal, for the financial support under the Project PTDC/BTM-SAL/29335/2017. Portugal 2020 for the Portuguese Mass Spectrometry Network (Rede Nacional de Espectrometria de Massa RNEM) is also acknowledged. The authors also acknowledge the Designer Nuno Monge for the artwork, Isabel Dias Nogueira (Microlab, Instituto Superior Técnico, Lisbon University) for the technical assistance with the SEM analysis, Andreia Bento for the assistance with the UHPLC-MS equipment (iMed.Ulisboa) and Professor Maria José Ferreira (FFULisboa) for allowing the use of the automatic flash chromatography equipment. Publisher Copyright: © 2022In clinic there is a demand to solve the drawback of medical devices multispecies related infections. Consequently, different biomaterial surfaces, such as vascular catheters, urgently need improvement regarding their antifouling/antimicrobial properties. In this work, we covalently functionalized medical grade polydimethylsiloxane (PDMS) with antimicrobial rhamnolipids to investigate the biomaterial surface activity towards mono and dual species biofilms. Preparation of surfaces with “piranha” oxidation, followed by APTES bonding and carbodiimide reaction with rhamnolipids effectively bonded these compounds to PDMS surface as confirmed by FTIR-ATR and XPS analysis. Generated surfaces were active towards S. aureus biofilm formation showing a 4.2 log reduction while with S. epidermidis and C. albicans biofilms a reduction of 1.2 and 1.0 log reduction, respectively, was observed. Regarding dual-species testing the higher biofilm log reduction observed was 1.9. Additionally, biocompatibility was assessed by cytocompatibility towards human fibroblastic cells, low platelet activation and absence of vascular irritation. Our work not only sheds light on using covalently bonded rhamnolipids towards dual species biofilms but also highlights the biocompatibility of the obtained PDMS surfaces.publishersversionpublishe

Fighting S. aureus catheter-related infections with sophorolipids: Electing an antiadhesive strategy or a release one?

Staphylococcus aureus medical devices related-infections, such as blood stream catheter are of major concern. Their prevention is compulsory and strategies, not prone to the development of resistance, to prevent S. aureus biofilms on catheter surfaces (e.g. silicone) are needed. In this work two different approaches using sophorolipids were studied to prevent S. aureus biofilm formation on medical grade silicone: i) an antiadhesive strategy through covalent bond of sophorolipids to the surface; ii) and a release strategy using isolated most active sophorolipids. Sophorolipids produced by Starmerella bombicola, were characterized by UHPLC-MS and RMN, purified by automatic flash chromatography and tested for their antimicrobial activity towards S. aureus. Highest antimicrobial activity was observed for C18:0 and C18:1 diacetylated lactonic sophorolipids showing a MIC of 50 μg mL−1. Surface modification with acidic or lactonic sophorolipids when evaluating the anti-adhesive or release strategy, respectively, was confirmed by contact angle, FTIR-ATR and AFM analysis. When using a mixture of acidic sophorolipids covalently bonded to silicone surface as antiadhesive strategy cytocompatible surfaces were obtained and a reduction of 90 % on biofilm formation was observed. Nevertheless, if a release strategy is adopted with purified lactonic sophorolipids a higher effect is achieved. Most promising compound was C18:1 diacateylated lactonic sophorolipid that showed no cellular viability reduction when a concentration of 1.5 mg mL−1 was selected and a reduction on biofilm around 5 log units. Results reinforce the applicability of these antimicrobial biosurfactants on preventing biofilms and disclose that their antimicrobial effect is imperative when comparing to their antiadhesive properties.The authors thank Fundação para a Ciência e Tecnologia (FCT) for the financial support under Projects PTDC/BTM-SAL/29335/2017, UIDB/04138/2020, UIDP/04138/2020 (iMed.ULisboa) and Portugal 2020 for the Portuguese Mass Spectrometry Network (Rede Nacional de Espectrometria de Massa RNEM; LISBOA 01 0145 FEDER 402 022125). The authors also acknowledge the Designer Nuno Monge for the artwork, Isabel Dias Nogueira (Microlab, Instituto Superior Técnico, Lisbon University) for the technical assistance with the SEM analysis, Joana Carola for the assistance with the UHPLC-MS equipment (iMed.Ulisboa) and Professor Rui Moreira (FFULisboa) for allowing the use of the automatic flash chromatography equipment. Moreover, this publication is partially based upon networking originated from COST Action "European Network of Multidisciplinary Research to Improve the Urinary Stents- CA16217", supported by COST (European Cooperation in Science and Technology). In memory of our Dear colleague and friend Judite.info:eu-repo/semantics/publishedVersio

Assuring the Biofunctionalization of Silicone Covalently Bonded to Rhamnolipids : Antibiofilm Activity and Biocompatibility

Silicone-based medical devices composed of polydimethylsiloxane (PDMS) are widely used all over the human body (e.g., urinary stents and catheters, central venous catheters stents) with extreme clinical success. Nevertheless, their abiotic surfaces, being prone to microorganism colonization, are often involved in infection occurrence. Improving PDMS antimicrobial properties by surface functionalization with biosurfactants to prevent related infections has been the goal of different works, but studies that mimic the clinical use of these novel surfaces are missing. This work aims at the biofunctional assessment of PDMS functionalized with rhamnolipids (RLs), using translational tests that more closely mimic the clinical microenvironment. Rhamnolipids were covalently bonded to PDMS, and the obtained surfaces were characterized by contact angle modification assessment, ATR-FTIR analysis and atomic force microscopy imaging. Moreover, a parallel flow chamber was used to assess the Staphylococcus aureus antibiofilm activity of the obtained surfaces under dynamic conditions, and an in vitro characterization with human dermal fibroblast cells in both direct and indirect characterization assays, along with an in vivo subcutaneous implantation assay in the translational rabbit model, was performed. A 1.2 log reduction in S. aureus biofilm was observed after 24 h under flow dynamic conditions. Additionally, functionalized PDMS lessened cell adhesion upon direct contact, while supporting a cytocompatible profile, within an indirect assay. The adequacy of the biological response was further validated upon in vivo subcutaneous tissue implantation. An important step was taken towards biofunctional assessment of RLs-functionalized PDMS, reinforcing their suitability for medical device usage and infection prevention