bims-livmat 2026-03-08 papers

Cell Rep. 2026 Mar 05. pii: S2211-1247(26)00142-7. [Epub ahead of print] 117064

Genetically engineered eye-colonizing microbes that deliver the anti-inflammatory cytokine interleukin-10 enhance corneal tissue repair.

Jackie Shane, Matthew Evans, Yannis Rigas, Robert M Q Shanks, Anthony J St Leger.

Barrier surfaces harbor tissue-colonizing microbes that can shape local physiology and immunity. During corneal injury, inflammation can delay healing, resulting in loss of visual acuity. Standards of care include topical applications of therapies, which are quickly washed away, requiring a laborious treatment regimen to maintain efficacy. To address this problem, we engineered an eye-colonizing microbe, Corynebacterium mastitidis, to act as a long-term therapeutic delivery vehicle by secreting bioactive interleukin (IL)-10 using a native secretion signal that we identified using transposon mutagenesis. Engineered microbes stably colonize the eye and release mouse (mIL-10) or human IL-10 (hIL-10) that modulates local immunity and accelerates wound repair after an initial inoculation event. Further, hIL-10 producing C. mast can regulate inflammatory cytokine production in immune cells, highlighting the immune-regulatory capabilities of this live biotherapeutic product. These findings demonstrate that genetically engineered eye-colonizing bacteria can serve as a self-sustaining therapeutic platform to control inflammation and promote tissue repair.

Keywords: CP: immunology; CP: microbiology; anti-inflammatory; cornea; live biotherapeutic; microbiome; ocular microbiome; ocular surface; paratransgenesis; transgenic microbiota

DOI: https://doi.org/10.1016/j.celrep.2026.117064

Curr Opin Microbiol. 2026 Mar 03. pii: S1369-5274(26)00021-4. [Epub ahead of print]91 102727

Advances in biocontainment strategies of engineered microbes for use in humans.

Jay Fuerte-Stone, Mark Mimee.

Genetically engineered microorganisms have been designed for use in many aspects of medicine. Advances in synthetic biology allow for the design of these organisms for a wide number of uses in a variety of environments. However, these advances are accompanied by the need for robust biocontainment strategies to prevent unwanted colonization and dissemination of engineered microorganisms. In this review, we discuss the current state of biocontainment strategies for use in biomedical applications. Many biocontainment strategies exist, including toxin-antitoxin systems, kill switches, auxotrophy, CRISPR-based targeted DNA degradation, nonstandard amino acids, and physical barriers. We discuss the use and caveats of these strategies both alone and in combination with each other. Additionally, we discuss the use and efficacy of these strategies in clinical trials. Finally, we discuss the need for standardized testing of containment escape. As use of these engineered microorganisms progresses, it is paramount that containment strategies advance with them to ensure safety, minimize environmental impact, and maintain a positive public view of this important work.

DOI: https://doi.org/10.1016/j.mib.2026.102727

Curr Opin Microbiol. 2026 Mar 03. pii: S1369-5274(26)00020-2. [Epub ahead of print]91 102726

Repurposing bacterial secretion systems for the design of living therapeutics.

Stevens Robertin, Cammie F Lesser.

The targeted delivery of therapeutics to sites of disease remains a major challenge. Almost all drugs, whether administered orally or intravenously, can cause systemic side effects. To circumvent these issues, synthetic biology-based approaches are being used to engineer bacteria to secrete therapeutic protein payloads directly at sites of disease. In the case of Gram-positive bacteria, the most straightforward approach has been to expand the repertoire of proteins recognized by their native protein secretion systems, which enable secretion across their cell membrane. However, for Gram-negative bacteria, these same secretion systems deposit proteins into the periplasm, the space between the two lipid bilayers of their complex outer envelope. Here, we review the ways that commensal and probiotic Escherichia coli are being engineered with additional secretion systems, including some originating from pathogens, outfitted to secrete desired therapeutic protein payloads. We discuss the potential advantages and limitations of each secretion system and potential areas for further investigation. Using examples of variants developed for the treatment of inflammatory bowel diseases, we provide a case study focused on the secretion systems, payloads, and transcriptional regulatory pathways that have been introduced. These studies demonstrate how advances in understanding bacterial secretion systems and synthetic biology are addressing therapeutic payload delivery challenges.

DOI: https://doi.org/10.1016/j.mib.2026.102726

Front Immunol. 2026 ;17 1698243

Targeted expression of the immunomodulatory peptide Scy by engineered Escherichia coli Nissle 1917 for alleviating enterotoxigenic E. coli infection.

Jie Fu, Lutong Zhou, Xiao Jiang, Hong Zhang, Yanli Chen, Lei Qiao, Deguang Song, Zeqing Lu, Tenghao Wang, Mingliang Jin, Caiqiao Zhang, Yizhen Wang, Yuanzhi Cheng.

Oral delivery of functional small peptides holds great promise for the prevention and treatment of intestinal diseases. However, their clinical application is limited by rapid degradation in the gastrointestinal tract, low bioavailability, and poor targeting capacity. To address these challenges, we engineered the probiotic Escherichia coli Nissle 1917 to express the immunomodulatory peptide Scy (EcN-Scy) under the control of the anaerobically responsive pNirB promoter, thereby enabling site-specific expression in the hypoxic intestinal environment. In vitro experiments demonstrated that EcN-Scy exhibited stable peptide expression and strong tolerance to heat, acid, bile salts, and simulated gastrointestinal fluids. In vivo, EcN-Scy administration caused no organ toxicity or metabolic abnormalities in mice, but significantly enhanced colonic antioxidant capacity, corrected the imbalance of Th1/Th2 cytokines, and maintained local immune homeostasis. 16S rDNA sequencing revealed that EcN-Scy reshaped the gut microbiota structure by increasing the abundance of beneficial genera such as Parabacteroides, while suppressing the proliferation of opportunistic pathogens including Alistipes and Muribaculaceae. In the enterotoxigenic Escherichia coli (ETEC) K88 infection model, EcN-Scy significantly alleviated diarrheal symptoms and colonic mucosal injury, enhanced the expression of barrier-associated proteins, and suppressed pro-inflammatory cytokine release in the gut. Compared with wild-type EcN, EcN-Scy exhibited markedly superior effects in anti-inflammatory, anti-infective, and barrier-protective functions. Collectively, EcN-Scy represents a novel peptide-producing engineered probiotic capable of targeted intestinal delivery and localized immune modulation, offering substantial potential as an oral microecological therapeutic for the management of intestinal inflammation and pathogen-induced infections.

Keywords: ETEC K88; Escherichia coli Nissle 1917; SCY; engineered probiotic; intestinal immunity; microbiota-based intervention; peptide delivery

DOI: https://doi.org/10.3389/fimmu.2026.1698243

Acta Biomater. 2026 Feb 28. pii: S1742-7061(26)00139-X. [Epub ahead of print]

White Light-Triggered Cascade NO/ROS-Releasing Platform with Synergistic Antibacterial and Angiogenic Effects for Infected Wound Healing.

Shanmin Tao, Miao Yang, Shijie Fu, Zhengwei Zhang, Ji Mu, Tianjiao Li, Xing Jiang, Yan Chen, Chengyuan Wang, Helin Niu, Peng Cao, Yali Liu.

Effective treatment of infected wounds requires concurrent control of microbes and restoration of vascular supply. Conventional therapies, including antibiotics and growth factors, suffer from limited efficacy and stability. Nitric oxide (NO) and reactive oxygen species (ROS) are promising alternatives that can eliminate bacteria and promote tissue regeneration. However, most current delivery systems use separate donors with simultaneous release, making control difficult and risking harmful peroxynitrite formation. Here, we report TPPF-NO, an organic small molecule based cascade NO/ROS donating platform activated by low-power white light (5 mW cm-2). Upon irradiation, TPPF-NO rapidly liberates NO, then converts into a photosensitizer (TPPF) that produces ROS in a controllable manner. Spectroscopy, Griess reaction analysis and electron paramagnetic resonance confirm the fast NO release and lightdriven ROS generation. Under mild illumination, TPPF-NO disrupt biofilms, enhance cell migration, and stimulate endothelial tube formation. Transcriptomic and validation studies confirm activation of IGF1-PI3K-AKT signaling and suppression of FoxO pathway. In infected mouse model, topical TPPF-NO with white light activation accelerates wound closure, reduces inflammation, and promotes neovascularization with favorable systemic safety. This controllable cascade NO/ROS releasing platform offers a promising and practical strategy for infected wound therapy and other situations requiring coordinated NO and ROS signaling. STATEMENT OF SIGNIFICANCE: Effective treatment of infected wounds remains a major clinical challenge due to bacterial resistance and delayed tissue regeneration. This work introduces a light-responsive molecule, TPPF-NO, which releases nitric oxide (NO) and reactive oxygen species (ROS) in a temporally separated manner. This cascade strategy enhances antibacterial efficacy while minimizing oxidative damage. Beyond disinfection, TPPF-NO promotes vascularized tissue regeneration by modulating immune response and activating the FOXO signaling pathway. These findings provide a novel paradigm for designing multifunctional wound therapies that couple infection control with tissue repair, offering broad relevance in biomaterials, phototherapy, and regenerative medicine.

Keywords: D-π-A scaffold; cascade releasing; infected wound healing; nitric oxide; reactive oxygen species

DOI: https://doi.org/10.1016/j.actbio.2026.02.054

Mater Today Bio. 2026 Apr;37 102938

Microalgal therapeutic peptides: From biomass to bone tissue engineering.

Diana Pacheco, Tatiana M F Patrício, Abílio J F N Sobral, Telma Encarnação.

Bone tissue engineering continues to face challenges in developing biomaterials that are both safe and biologically active, particularly in promoting integration with native tissue. Traditional synthetic materials often lack cellular compatibility, driving research toward natural and biomimetic alternatives. In this context, microalgae have a diverse metabolic profile, producing several biologically active compounds (i.e. lipids, carbohydrates, pigments) with therapeutic potential for bone regeneration. Among these, peptides gain relevance due to their high cellular compatibility, osteogenic activity and tunable properties. Herein, this review provides a comprehensive and critical overview of microalgae-derived peptides, covering their manufacturing process. It covers the entire workflow from protein extraction to peptide purification and characterization. It summarizes their biological properties and therapeutic applications in bone regeneration and examines their status in clinical studies alongside the main regulatory and translational challenges. Particular focus will be given to the combination of advanced delivery systems for using microalgae therapeutic peptides to develop patient-specific implants. Overall, this review emphasizes the significance of microalgae as a versatile and sustainable resource to extract therapeutic peptides and to develop the next generation of biomaterials in bone regenerative medicine.

Keywords: Advanced delivery systems; Bioactive compounds; Biomimetic; Bone regeneration; Therapeutic peptides

DOI: https://doi.org/10.1016/j.mtbio.2026.102938