BURA Collection:

Hydrogels Augmented With Artificial Sweeteners can Inhibit Multidrug‐Resistant Acinetobacter baumannii Growth and Biofilm Formation While Demonstrating Safety in Pre‐Clinical Pilot Human Trials

2026-08-26T00:00:00Z

Title: Hydrogels Augmented With Artificial Sweeteners can Inhibit Multidrug‐Resistant Acinetobacter baumannii Growth and Biofilm Formation While Demonstrating Safety in Pre‐Clinical Pilot Human Trials Authors: Han, Jie; Soliman, Mohamed; Zhang, Bin; Krawiel, Dominika; McCarthy, Ronan R Abstract: There is a critical need for novel therapeutic strategies to tackle multidrug‐resistant bacterial infections. Artificial sweeteners (AS) specifically acesulfame potassium, sodium saccharin, and sodium cyclamate, have recently demonstrated antimicrobial activity against multidrug‐resistant bacteria. In this study, polyvinyl alcohol (PVA)‐borate hydrogel is developed as a carrier for antimicrobial AS to combat wound infections. Through extensive optimization, we developed cytocompatible 8% AS‐loaded hydrogels with 3% PVA + 3% borax that reduced the viability of multidrug‐resistant Acinetobacter baumannii AB5075 by 99.9% colony‐forming unit enumeration following 1 h hydrogel treatment. Most currently available wound dressings have limited efficacy against bacterial biofilms, but we demonstrate that each of these sweeteners can attenuate A. baumannii and Pseudomonas aeruginosa dual‐microbial biofilms. Haemolysis and cell viability assays demonstrate excellent blood compatibility and non‐cytotoxic behavior of the sweetener‐loaded hydrogels. To further evaluate the clinical potential of these AS‐loaded hydrogels, we conducted a pilot Phase I clinical study with human volunteers focused on evaluating short‐term safety and irritancy. This study revealed that the dressings had no adverse effects on the volunteers. This research underscores the translational potential of hydrogels augmented with AS and their capacity to overcome many of the hurdles that typically lead to wound dressing failure. Description: Data Availability Statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.

Dysregulation of sphingolipid-metabolizing enzymes in Friedreich’s ataxia: In vitro and in vivo insights into therapeutic targeting

2026-06-22T00:00:00Z

Title: Dysregulation of sphingolipid-metabolizing enzymes in Friedreich’s ataxia: In vitro and in vivo insights into therapeutic targeting Authors: Ramchunder, Z; Kalef-Ezra, E; Suleman, S; Edzeamey, FJ; Szunyogh, S; Gittins, O; Mena, NC; Wade-Martins, R; Valle, A; Pourzand, C; Anjomani Virmouni, S Abstract: Friedreich’s ataxia (FRDA) is an inherited neurodegenerative disorder caused by a GAA repeat expansion within the FXN gene, leading to reduced frataxin levels. This deficiency results in mitochondrial dysregulation, oxidative stress, and progressive cell death. Currently, only one approved treatment exists for FRDA in the United States, Canada, and the European Union, which improves neurological outcomes but has not been fully evaluated for broader disease symptoms. Therefore, identifying new therapeutic targets remains essential. Sphingolipids are increasingly recognized for their roles in neurodegeneration with emerging evidence indicating their dysregulation in FRDA. Here, we investigate whether sphingolipid-metabolizing enzymes are similarly affected and assess the therapeutic potential of targeting them. Our findings demonstrate that these enzymes are dysregulated across multiple FRDA models. Importantly, their modulation in vitro and in vivo significantly reduces mitochondrial dysfunction, enhances frataxin expression, and improves key pathological features of the disease, highlighting sphingolipid metabolism as a promising therapeutic target for FRDA. Description: Data and code availability: • All data reported in this paper will be shared by the lead contact upon request. • This paper does not report original code. • Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Immune dysregulation in tuberculosis-diabetes comorbidity: mechanistic and translational insights

2026-04-23T00:00:00Z

Title: Immune dysregulation in tuberculosis-diabetes comorbidity: mechanistic and translational insights Authors: Saula, AY; Cevik, M; Cliff, JM; Ronacher, K; Bowness, R Abstract: Background: Tuberculosis (TB) remains a leading cause of infectious disease mortality worldwide, and the rising prevalence of diabetes mellitus (DM) represents a major obstacle to TB control. DM increases susceptibility to TB, worsens disease severity, delays treatment response, and is associated with poorer outcomes, largely through disruption of host immunity. Methods: We conducted a systematic review of studies published between 1974 and May 31, 2023 that examined immunological mechanisms through which DM alters TB pathogenesis. In total, 81 eligible studies involving animal models, human participants, or combined approaches were identified and synthesised across different stages of TB. Results: Across studies, DM was associated with broad dysregulation of innate and adaptive immune responses, altered cytokine signalling, impaired granuloma structure and function, and reduced control of Mycobacterium tuberculosis (Mtb). Distinct immune profiles emerged between TB disease with DM and latent TB infection with DM, with heterogeneity partly explained by differences in study design, metabolic status, and disease stage. Importantly, emerging evidence indicates that pre-diabetes and intermediate hyperglycaemia may also compromise TB immunity and contribute to disease progression. Conclusion: Our findings highlight DM as a key immunometabolic modifier of TB pathogenesis. They also suggest that earlier metabolic optimisation and hostdirected therapeutic strategies could be explored as potential approaches to improve outcomes in this growing high-risk TB-DM population. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023431040. Description: Data availability statement: The data analyzed in this study is subject to the following licenses/restrictions: The datasets can be shared with researchers upon request. Requests to access these datasets should be directed to Aminat Y. Saula, ays27@bath.ac.uk.; Supplementary material: The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fimmu.2026.1803046/full#supplementary-material .

CAR-mediated release of IL-10 increases the function of regulatory T cells: relevance for future clinical application

2026-02-06T00:00:00Z

Title: CAR-mediated release of IL-10 increases the function of regulatory T cells: relevance for future clinical application Authors: Saleem, A; Peng, Q; Tang, Z; Mohseni, YR; Scottà, C; Shangaris, P; Smit, K; Vermeij, WP; Issa, F; Lombardi, G; Fruhwirth, GO Abstract: Regulatory T cell (Treg) therapy emerges for various indications associated with a breakdown of immune tolerance. Antigen-specific chimeric antigen receptor (CAR) Tregs are frontrunners for transplantation and autoimmune diseases and are currently being clinically evaluated. We aimed to link CAR-antigen engagement with immunosuppressive cargo release into the local microenvironment to boost efficacy and reduce side effects. We used our HLA-A∗02 CAR and immunosuppressive interleukin-10 (IL-10) as model components to generate human CAR Tregs that release IL-10 upon CAR engagement. These were compared to CAR Tregs with constitutive or no IL-10 expression by evaluating phenotypes, antigen-specific IL-10 release, and suppression of effector cell proliferation in vitro and performance in vivo in a humanized xenogeneic graft-versus-host disease (xeno-GvHD) model. We demonstrated successful multi-construct engineering of CAR Tregs, which released upon CAR engagement 2.5-fold more IL-10 than CAR Tregs lacking the corresponding antigen-specific IL-10 secretion module. Neither phenotype nor function was affected by expressing this module. In the xeno-GvHD model, we showed the beneficial effect of IL-10 release, particularly evident when compared to constitutive IL-10 expression that impaired CAR-Treg efficacy. We provide first proof-of-principle for engineering human CAR Tregs to release an immunosuppressive cytokine upon CAR engagement. This approach will both enhance the potency of CAR Tregs at the intended target sites and limit their off-target effects. Description: Data and code availability: The data presented here are available on request from the corresponding authors.; Supplemental information is available online at: https://www.sciencedirect.com/science/article/pii/S1525001626000870#appsec2 .