bims-livmat 2026-07-12 papers

Curr Opin Microbiol. 2026 Jul 10. pii: S1369-5274(26)00083-4. [Epub ahead of print]93 102789

Unleashing the potential of S-layer proteins for engineered living materials.

Chloe Ha Chau Nguyen, Olivia Suggs, Caroline M Ajo-Franklin.

The field of engineered living materials (ELMs) aims to create self-regenerative, self-assembled, and multifunctional materials that mimic natural biomaterials. Novel ELMs can be produced by engineering biomolecules that are naturally secreted and displayed on bacterial cell surfaces. Surface-layer (S-layer) proteins are a class of proteins that form a two-dimensional paracrystalline lattice on the surface of many prokaryotes. These proteins provide a secretion, surface-anchoring, and high-density display platform that can be exploited for material formation. In this review, we discuss two strategies to engineer S-layer proteins for ELMs by looking at their state of the art, analyzing their advantages and disadvantages, and discussing their challenges and opportunities.

DOI: https://doi.org/10.1016/j.mib.2026.102789

J Appl Microbiol. 2026 Jul 07. pii: lxag161. [Epub ahead of print]

Bioactive environments to combat antimicrobial resistance: artificial intelligence and model-driven microbial biocontrol for living materials.

Kathleen L Furtado, Jack A Gilbert, Maxwell Neal.

Antimicrobial resistance (AMR) continues to outpace development of new therapeutics. Many interventions focus on treating infection after it occurs, but resistant pathogens often emerge, persist, and spread within reservoirs, such as built environments. Microbial biocontrol offers a complementary, upstream strategy by reshaping ecological interactions to suppress the colonization, persistence, and transmission of AMR pathogens. Currently, biocontrol design relies upon the presumed functionality of probiotic genera across diverse environments despite limited experimental validation, alongside heuristic model predictions that prioritize efficiency over sensitivity. These approaches yield inconsistent outcomes, reflecting the context-dependent nature of microbial behavior. We review how advances in metabolic modeling and artificial intelligence (AI), in conjunction with experimental data, enable adaptable, context-aware biocontrol design with iterative design-test-learn cycles for optimization. We outline the ecological principles underlying microbial competition, highlighting Bacillus as a robust biocontrol chassis due to its biosynthetic capacity, stress tolerance, and genetic tractability. We then discuss how genome-scale, pan-genome-scale, and metabolism-and-expression models provide mechanistic insight into competitive fitness, metabolic trade-offs, and persistence. AI advances these approaches by extracting patterns from multi-omic datasets to build specific, yet versatile, foundation models (FMs) that guide strain and/or consortium selection for specific built environments. Moreover, these tools facilitate safe biocontrol deployment by enabling risk assessment of persistence, ecological displacement, and horizontal gene transfer (HGT), particularly for engineered living materials (ELMs) and bioactive building surfaces. Ultimately, AI-guided modeling and systems-level design provide scalable frameworks for developing durable, preventive strategies against AMR, shifting the focus from reactive treatment toward proactive control of pathogen ecology.

Keywords: artificial intelligence; engineered living materials; foundation models; genome-scale metabolic models; metabolism and expression models; probiotics

DOI: https://doi.org/10.1093/jambio/lxag161

J Hematol Oncol. 2026 Jul 07.

From tumor targeting to tumor accessibility: surface-engineered bacteria as precision living therapeutics for translational medicine.

Liyuan Qiao, Leyang Wu, Yihan Xiao, Jiahui Qiu, Xinyue Qiao, Xiao Dong, Chengxuan Lei, Wanru Wang, Yuzi Zhao, Zichun Hua.

The concept of bacterial therapy dates back over a century to clinical observations that incidental infections could induce tumor regression. Recent advances in genetic engineering and synthetic biology have since transformed bacteria into versatile living therapeutics with significant preclinical potential against diseases such as cancer, inflammatory disorders, and metabolic conditions. However, clinical translation faces considerable hurdles. Here, we provide a clinically oriented perspective on the translational gap in bacterial therapy. Drawing inspiration from the success of antibody-drug conjugates in achieving precise payload delivery, we highlight an emerging paradigm of "precision living therapeutics" enabled by bacterial surface engineering. we propose the concept of "Tumor accessibility" for the first time, and identify its insufficiency as a critical bottleneck in current therapeutic applications. We then systematically summarize recent advances in bacterial surface engineering, encompassing physical, chemical, and biological strategies, with a focus on their capacity to evade immune clearance, enhance tumor colonization, and improve therapeutic performance. Chemical approaches primarily involve covalent conjugation, including the SpyTag/SpyCatcher system and bioorthogonal click chemistry-based metabolic labeling. Physical strategies center on cell membrane encapsulation and surface coatings such as layer-by-layer encapsulation. Biological strategies include cell camouflage and genetic modulation of surface structures, display of functional biomolecules, and affinity-based systems such as biotin-streptavidin interactions. Finally, we discuss integrative strategies that combine surface-engineered bacteria with conventional treatment modalities, including physical therapy, chemotherapy, and immunotherapy. We propose that future clinical translation of bacterial therapy should shift from localized modification design to a holistic consideration of systemic accessibility.

Keywords: Bacterial clinical translation; Bacterial therapeutics; Cancer immunotherapy; Cellular camouflage; Surface modification

DOI: https://doi.org/10.1186/s13045-026-01827-1

Cell Host Microbe. 2026 Jul 08. pii: S1931-3128(26)00218-0. [Epub ahead of print]34(7): 1241-1261

Engineering commensal microbes for host health.

Elizabeth A Brown, Arianna Brevi, David M Zong, Amir Zarrinpar.

Engineered live biotherapeutic products (eLBPs) represent an emerging class of programmable microbial therapies capable of sensing and responding to host physiology. Advances in microbiome science and synthetic biology have driven the development of engineered bacteria that deliver therapeutic molecules, modulate host metabolism, or detect disease-associated signals. In this review, we summarize recent progress in the development of eLBPs across diverse disease indications, including inflammatory diseases, metabolic disorders, cancer, and infectious diseases. We highlight key factors that drive successful eLBP design, including chassis selection, methods for DNA delivery, approaches for tuning therapeutic expression, and genetic systems for biocontainment. Although early clinical studies demonstrate promising safety profiles, challenges remain in achieving predictable colonization, durable therapeutic activity, and robust biocontainment in vivo. By synthesizing advances across these areas, we propose a framework for the rational design of next-generation eLBPs that can more reliably translate from experimental systems to clinical application.

Keywords: CRISPR-associated transposases; Engraftment; Escherichia coli Nissle 1917; Quorum sensing; auxotrophy; calprotectin; curli fibers; horizontal gene transfer; kill switches; memory circuits; mucosal delivery; porphyrin

DOI: https://doi.org/10.1016/j.chom.2026.05.025

Front Biosci (Elite Ed). 2026 Jun 01. 18(2): 44545

Biotechnologically Derived Materials as Drug Delivery Systems for Tissue Regeneration.

Sorur Yazdanpanah, Silvia Romano, Umberto Galderisi, Fabrizia Sepe, Gianfranco Peluso, Raffaele Conte, Anna Calarco.

Regenerative medicine is an evolving field that seeks to restore or replace damaged tissues and organs through the activation of endogenous repair pathways or the application of engineered therapeutic strategies. Within this paradigm, drug delivery systems (DDSs) serve as essential mediators for localized, sustained, and controlled release of bioactive agents that stimulate and support tissue regeneration. The advent of biotechnology has catalyzed the development of innovative DDSs based on biologically derived materials, offering improved biocompatibility, biodegradability, and functional versatility. This review presents a critical analysis of recent advances in the design and application of biotechnologically derived materials, such as recombinant collagen, elastin, and silk, as well as microbial biosynthesized polysaccharides, including bacterial cellulose, hyaluronic acid, and alginate, as drug delivery platforms in regenerative medicine. Thus, a systematic approach was adopted based on recent peer-reviewed studies to evaluate the physicochemical properties and biofunctional characteristics of these materials. The results indicate that recombinant proteins offer tunable mechanical and biochemical properties, exhibit tunable mechanical moduli ranging from ~0.5 to 50 kPa, mimicking native extracellular matrix components; meanwhile, microbial polysaccharides demonstrate high water retention (above 90%), structural flexibility, and bioadhesive potential, making these polysaccharides highly suitable for soft tissue engineering. These materials also enable encapsulation of growth factors, nucleic acids, and small-molecule drugs, facilitating spatiotemporal release and degradation half-lives between 1 and 6 weeks, aligned with tissue-specific repair processes. Therefore, biotechnologically derived DDSs represent a promising frontier for regenerative medicine, merging the precision of recombinant engineering with the scalability of microbial fermentation.

Keywords: biopolymers; controlled release; drug delivery systems; microbial biosynthesis; recombinant proteins; regenerative medicine; scaffold integration; tissue engineering

DOI: https://doi.org/10.31083/FBE44545