bims-livmat 2025-07-06 papers

J Nanobiotechnology. 2025 Jul 01. 23(1): 463

Alternating magnetic field-responsive engineered probiotics for anxiety therapy via gut-brain axis modulation.

Xuejun Wang, Yuhan Zhang, Yuling Chang, Yuhao Zhu, Guo Xiang, Kehua Chen, Chuanxing Feng, Zhaofang Hang, Xingang Li, Di Zhang.

The discovery of the gut-brain axis demonstrated bidirectional regulation between the gut and the brain. The gastrointestinal branches of the vagal nerve have been proven to directly modulate multiple functions of the central nervous system (CNS), providing great opportunities to develop novel tools to remotely regulate CNS function from the gut. Engineered bacteria, acting as oral live biotherapeutics, offer a durable and controllable way of modulating neuronal function non-invasively and with low side effects. Here, we constructed an engineered bacterium by genetically modifying Escherichia coli Nissle 1917 (EcN) with Fe3O4 nanoparticles to release gamma-aminobutyric acid (GABA) under the control of the alternating magnetic fields (AMF). Bioavailability, assessed by survival rate in artificial gastric fluid, was further enhanced by encapsulating EcN with a poly-norepinephrine (NE) layer, which protected the probiotics from environmental stress and improved their viability during oral delivery. The oral administration of the EcN-GadABC@Fe-NE/AMF in restraint mice exhibited significant anxiolytic efficacy, which was attenuated by the chemogenetic counteraction of vagal sensory inhibition. Immunohistochemistry staining against c-fos showed reduced neuronal activation in both the nucleus of the solitary tract (NTS) and locus coeruleus (LC) area in the restraint mice treated by the EcN-GadABC@Fe-NE/AMF. Furthermore, acting as a probiotic, the EcN-GadABC@Fe-NE modulated gut microbiota homeostasis, additionally contributing to the alleviation of anxiety-like behaviors. This approach opens up a novel revenue for developing remote and non-invasive methods to modulate CNS function from the gut, and enhancing bacteriotherapy for mental disorders.

Keywords: Anxiety therapy; Engineered bacteria; Gastrointestinal vagal afferents; Gut-brain axis; Nanomaterials

DOI: https://doi.org/10.1186/s12951-025-03551-3

ACS Synth Biol. 2025 Jul 03.

Engineered Lactiplantibacillus plantarum WCFS1 as a Biosensor Probe for Lung Cancer.

Michael Brasino, Eli Wagnell, Elise C Manalo, Samuel Drennan, Jared M Fischer, Justin Merritt.

Lung cancer is exceedingly difficult and costly to detect early, leading to delayed diagnosis, limited treatment options, and high patient mortality. Tumor-secreted molecules are useful in identifying early disease but are difficult to detect when diluted in accessible bodily fluids. Here, we demonstrate a low-cost, minimally invasive method to probe the lungs for disease using genetically engineered Lactiplantibacillus plantarum bacteria as living biosensors. When delivered to the lungs of mice, the engineered bacteria remained transcriptionally active for several hours and were cleared without colonization. Nanoluciferase secreted by bacteria from within the lungs was subsequently detected in mouse urine. Bacteria were engineered to secrete nanoluciferase in response to a model peptide excreted by a mouse lung cancer cell line, allowing the bacteria to detect tumors formed from these cells in the lungs of mice. Finally, biosensor bacteria were also able to detect a secreted protease overexpressed in adenocarcinoma using a probe protein that is cleaved to release a bacterial pheromone peptide. These results indicate that genetically engineered commensal bacteria yield tremendous promise as living biosensors for early detection screens of lung cancer.

Keywords: Lactiplantibacillus plantarum; MMP13; biosensor; lung cancer; nanoluciferase; synthetic biomarker

DOI: https://doi.org/10.1021/acssynbio.5c00186

Protein Pept Lett. 2025 Jul 02.

Engineered Bacteriophages: Advances in Phage Genome Redesign Strategies for Therapeutic and Environmental Applications.

Marzieh Rezaei, Amir Jalali, Dheyaa Hussein Sadah Al-Azzawi.

Bacteriophages, or phages, have emerged as powerful platforms in synthetic biology, offering innovative solutions for therapeutic and environmental challenges through advanced genome redesign strategies. This review explores a wide range of phage engineering techniques, including CRISPR (clustered regularly-interspaced short palindromic repeats)-Cas systems, phage display, random and site-directed mutagenesis, retrons, and rebooting approaches, highlighting their potential to create phages with tailored functionalities. CRISPR-Cas systems enable precise genome editing, allowing the development of phages with expanded host ranges, biofilm degradation capabilities, and targeted antimicrobial activity. Phage display facilitates the presentation of peptides on phage surfaces, enabling applications in targeted drug delivery, tumor imaging, and bioremediation. Beyond these, techniques like retron-mediated recombination and homologous recombination offer additional avenues for precise phage genome modification. In the therapeutic realm, engineered phages show promise in combating drug-resistant infections, modulating the microbiome, and delivering targeted therapies for cancer and other diseases. Environmentally, phage-based strategies, such as the use of phage-displayed metal-binding peptides, provide innovative solutions for bioremediation and reducing exposure to toxic heavy metals. This review also addresses challenges, such as phage resistance, immune responses, and the limitations of current engineering methods, while exploring future directions, including the development of improved CRISPR systems, phage-based biosensors, and high-throughput screening platforms. By integrating cutting-edge genome redesign strategies with diverse applications, this review underscores the transformative potential of engineered bacteriophages in addressing global healthcare and environmental sustainability challenges.

Keywords: Engineering; bacteriophage genome; environmental safety.; peptide display; redesigning; therapeutic applications

DOI: https://doi.org/10.2174/0109298665372719250616085616

Science. 2025 Jul 03. 389(6755): 37-38

The vaccine we all wear: Skin microbiota can be engineered into topical vaccines.

Djenet Bousbaine.

Skin microbiota can be engineered into topical vaccines.

DOI: https://doi.org/10.1126/science.adz0485