bims-livmat Biomed News
on Living materials
Issue of 2025–12–28
six papers selected by
Sara Trujillo Muñoz, Leibniz-Institut für Neue Materialien
  1. Engineered Stable, Antibiotic-Free, High-Level Protein Expression in the Probiotic Chassis Escherichia coli Nissle 1917.
  2. Engineered probiotics platform for oral delivery of antibody as a high-compliance alternative for immune-mediated inflammatory diseases.
  3. Tunable light-focusing behavior of engineered bacterial microlenses with controllable shapes.
  4. Synthetic biology strategies for engineering probiotics and commensal bacteria for diagnostics and therapeutics.
  5. Engineering microbes to modulate innate immune signaling: strategies for host-microbe interactions.
  6. Manufacturing of Living Building Materials With Calcifying Cyanobacteria.
  1. Biotechnol Bioeng. 2025 Dec 24.
    Engineered Stable, Antibiotic-Free, High-Level Protein Expression in the Probiotic Chassis Escherichia coli Nissle 1917.
    Halimatun Sakdiah Zainuddin, Sanjeeva Kumar Murali, Thomas J Mansell.
      The application of engineered live biotherapeutic products (LBPs) to secrete small molecules, peptides, or proteins to benefit a human or animal host, relies on heterologous protein expression. Key challenges in this area include expressing protein in a targeted location, the use of antibiotic-free platforms, and expressing recombinant proteins at titers capable of the desired therapeutic effect. In this study, we sought to engineer the promising candidate probiotic chassis Escherichia coli Nissle 1917 (EcN) as an in situ drug delivery platform. Despite its long history of safe human use and general probiotic characteristics, wild-type EcN is not optimal for routine protein expression. In this work, we present several approaches to improve protein production in this host. First, we enable stable antibiotic-free protein expression system via native cryptic plasmids. Next, we integrate the T7 RNA polymerase for high level protein expression. Finally, we knock out OmpT protease activity, enabling expression levels comparable to the industry standard E. coli BL21 (DE3). To demonstrate its application, the above system was adapted to express antimicrobial peptide microcin L (MccL) from EcN, which can potentially reduce gut related pathogens and enhance fitness of the probiotic in the competitive niche of the gut. Overall, this study establishes an antibiotic free and high level protein expression platform in EcN, expandable for in situ delivery of therapeutic proteins.
    Keywords:  E. coli Nissle 1917; antibiotic free protein expression; anti‐microbial peptide; probiotics; protein expression; therapeutic protein
    DOI:  https://doi.org/10.1002/bit.70130
  2. Cell Rep Med. 2025 Dec 19. pii: S2666-3791(25)00596-8. [Epub ahead of print] 102523
    Engineered probiotics platform for oral delivery of antibody as a high-compliance alternative for immune-mediated inflammatory diseases.
    Jia Liu, Lexuan Wang, Bingyu Pang, Yichenxi Shi, Yang Chen, Ruili Zhang, Shuai Shao, Chaoqiang Qiao, Zhongliang Wang.
      Antibody-based therapies have transformed the management of immune-mediated inflammatory diseases (IMIDs), but the need for frequent injections often leads to inadequate patient adherence and suboptimal long-term disease control. To address this challenge, we develop AIDEN (aid for IMIDs: engineered EcN), an engineered probiotic platform that enables oral delivery of therapeutic antibodies using synthetic biology. In this study, we assess the efficacy of AIDEN-IL17, a variant designed to secrete single-chain variable fragments targeting interleukin-17A (IL-17A), in murine models of psoriasis and inflammatory bowel disease. AIDEN-IL17 exhibits stable gut colonization and sustained in situ antibody production, resulting in moderate reduction of systemic IL-17A levels and significant amelioration of disease symptoms. Notably, the AIDEN platform is modular and adaptable for delivering a broad range of antibody therapeutics, offering a promising, patient-friendly strategy for the treatment of IMIDs.
    Keywords:  engineered probiotics; immune-mediated inflammatory diseases; oral antibody delivery; psoriasis
    DOI:  https://doi.org/10.1016/j.xcrm.2025.102523
  3. bioRxiv. 2025 Dec 17. pii: 2025.12.17.694918. [Epub ahead of print]
    Tunable light-focusing behavior of engineered bacterial microlenses with controllable shapes.
    Lynn M Sidor, Kathren P Sage, Michelle M Beaulieu, Dylan F Wilson, Emerson Jenen, B Cansu Acarturk, Wil V Srubar, Greg R Schmidt, Elio A Abbondanzieri, Anne S Meyer.
      Recently, engineered bacterial cells have been shown to behave as optically-active photonic devices comparable to industrially fabricated microlenses 1 . Bacterial cells can be encapsulated within a layer of polysilicate through surface display of the sea sponge enzyme silicatein, which mineralizes a polysilicate coating. The addition of this polysilicate layer significantly enhances the ability of these cells to guide, scatter, and focus light 1 . However, this previous technique was limited to creating rod-shaped microlenses, which are not ideal for all applications. Here we expand upon this technology by engineering the shapes of silicatein-displaying bacterial cells. Through the overexpression of the genes bolA 2-5 and sulA 6,7 or through the use of the drug A22 8,9 , we are able to alter Escherichia coli cells from their characteristic rod-like shape to either spherical or filamentous forms. Round cells encapsulated in polysilicate were shown to scatter light more intensely and symmetrically than rod-shaped cells, while encapsulated filamentous cells were shown to guide light similarly to an optical fiber. This control over the size and shape of optically-active cells is a major advancement towards developing bio-engineered photonic devices such as nanophotonic waveguides, spherical microlens arrays, and advanced biosensors.
    DOI:  https://doi.org/10.64898/2025.12.17.694918
  4. Biotechnol Adv. 2025 Dec 18. pii: S0734-9750(25)00268-X. [Epub ahead of print]87 108782
    Synthetic biology strategies for engineering probiotics and commensal bacteria for diagnostics and therapeutics.
    Jiwoo Nam, Yuna Lee, Sion Lee, Hyungjun Choi, Sang Yup Lee, Dongsoo Yang.
      Microorganisms inhabit diverse environments, including nearly every organ in the human body. The human microbiome-a complex community of microorganisms residing in the human body-has gained increasing attention as a key contributor to human health and disease, making it an important target for the development of diagnostic and therapeutic strategies. However, the inherent complexity of microbial communities and the challenges of engineering diverse non-model microorganisms present significant barriers. To address these challenges, synthetic biology has provided powerful tools and strategies to engineer microorganisms capable of sensing disease-specific environments and performing targeted therapeutic functions. In particular, the development of synthetic genetic circuits has significantly improved the precision and reliability of disease diagnosis and treatment, enabling real-time disease monitoring, therapeutic, and even preventive interventions. This review highlights state-of-the-art synthetic biology tools and strategies for engineering the probiotics and commensal bacteria aimed at the diagnosis and treatment of human diseases, with accompanying examples. Future challenges and prospects are also discussed.
    Keywords:  Diagnostics; Microbiome; Probiotics; Synthetic biology; Therapeutics
    DOI:  https://doi.org/10.1016/j.biotechadv.2025.108782
  5. Curr Opin Microbiol. 2025 Dec 22. pii: S1369-5274(25)00117-1. [Epub ahead of print]89 102695
    Engineering microbes to modulate innate immune signaling: strategies for host-microbe interactions.
    Shanna Bonanno, Neel S Joshi.
      The human gastrointestinal tract hosts a dense microbial community that closely interfaces with the mucosal immune system to preserve homeostasis. While dysregulation of this interaction contributes to certain disease states, through targeted microbial engineering, these interactions can be modulated for therapeutic benefit. Although engineered microbial therapeutics have shown encouraging preclinical results, few approaches have progressed into clinical pipelines. This gap highlights the need for engineered microbes with greater precision, reliability, and context-dependent control. The innate immune system is primed to rapidly sense microbial signals through pattern recognition receptors and provides accessible and tractable targets for such interventions. This review highlights four strategies that have used engineered probiotics to modulate innate immunity: (1) direct immune cell engagement through surface-display, (2) production of soluble immune effectors, (3) extracellular vesicles for delivery of immune modulators, and (4) environmentally responsive systems to enable spatial and temporal control over immune modulation. Bridging microbial engineering with mucosal immunology can enable engineered probiotics to function as dynamic, context-aware immunomodulators.
    DOI:  https://doi.org/10.1016/j.mib.2025.102695
  6. Bio Protoc. 2025 Dec 20. 15(24): e5543
    Manufacturing of Living Building Materials With Calcifying Cyanobacteria.
    Patrick Jung, Jan Friedek, Laura Briegel-Williams, Miriam Haage-Ott, Carina Neff.
      In recent years, the calcifying properties of some cyanobacteria have been used in the production of living building materials (LBMs), such as bio-concrete, as a CO2-friendly alternative for cement. This microbially induced calcium carbonate precipitation (MICP) technique can act as a novel platform technology for carbon capture strategies. Consequently, various research articles have been conducted based on a diverse set of workflows, including several modifications, to manufacture LBMs. However, such articles contain only fragmentary descriptions of the materials and methods used. This protocol is meant to act as a detailed, step-by-step operational manual for the production of LBMs using the cyanobacterial model strain Picosynechococcus sp. PCC 7002. The process is divided into several steps, such as the activation of the cyanobacterial-gel solution with CaCl2 × 2H2O and NaHCO3, casting standardized prisms (160 × 40 × 40 mm), and demolding LBMs. Subsequently, bending tensile and compressive strength tests are performed according to the procedures commonly used in concrete and material testing as proof of concept. Key features • A comprehensive workflow for the manufacturing of cement-free living building materials with cyanobacteria. • A cyanobacteria-gelatin-containing solution is activated, mixed with sand, casted, curated, and strength tested. • Adaptable for other cyanobacterial strains and substitute materials.
    Keywords:  Calcification; Cement; Concrete; Cyanobacteria; Living building material
    DOI:  https://doi.org/10.21769/BioProtoc.5543
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