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Engineered probiotics

François P Douillard, Willem M de Vos
Over the last decade, there has been an increasing scientific and public interest in bacteria that may positively contribute to human gut health and well-being. This interest is reflected by the ever-increasing number of developed functional food products containing health-promoting bacteria and reaching the market place as well as by the growing revenue and profits of notably bacterial supplements worldwide. Traditionally, the origin of probiotic-marketed bacteria was limited to a rather small number of bacterial species that mostly belong to lactic acid bacteria and bifidobacteria...
March 12, 2019: Biotechnology Advances
Xin Fang, Puyuan Tian, Xiaoxiao Zhao, Chunling Jiang, Tingtao Chen
While glucagon-like peptide-1 (GLP-1) was reported to have a positive impact on Parkinson disease, its extremely short half-life greatly hindered its clinical use. In the present study, the mouse strain MG1363-pMG36e-GLP-1 was engineered to continuously express GLP-1 to treat Parkinson disease in a 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-treated Parkinson disease model. In our study, oral supplementation with MG1363-pMG36e-GLP-1 significantly (p < 0.05) reduced MPTP-induced locomotor impairments, increased tyrosine hydroxylase (T-OH)-positive neurons, suppressed microglia and astrocyte activation and downregulated expression of several inflammation-related molecules...
March 9, 2019: Journal of Neurochemistry
Meng-Xin Hu, Ji-Nian Li, Qian Guo, Ya-Qian Zhu, Hong-Mei Niu
Electrospun nanofiber membranes are widely investigated in the past few decades as candidates for tissue engineering, which can mimic natural extracellular matrix (ECM) and improve cell adhesion, proliferation, and expression on nanofiber membranes. However, the formation of bacterial biofilms on nanofiber membranes and application of the biofilm-integrated nanofiber membranes remain largely unknown. Here, electrospun cellulose acetate nanofiber membranes are first utilized as scaffold materials for Lactobacillus plantarum ( L...
March 6, 2019: Journal of Agricultural and Food Chemistry
Saša Simčič, Aleš Berlec, Sanja Stopinšek, Borut Štrukelj, Rok Orel
Dysbiosis of intestinal microbiota and aberrant inflammatory responses in gastrointestinal mucosa plays important roles in the development of inflammatory bowel disease (IBD). The purpose of this study was to demonstrate the probiotic activity of Lactococcus lactis and the ability of TNF-α-binding by recombinant L. lactis bearing TNF-α-binding affibodies. Various concentrations of recombinant L. lactis were exposed to TNF-α and its binding measured by ELISA. Mucosal biopsies of patients with active IBD were incubated with various L...
February 27, 2019: World Journal of Microbiology & Biotechnology
Xuwen Gao, Yingying Ma, Zhuo Wang, Jing Bai, Shuo Jia, Baohua Feng, Yanping Jiang, Wen Cui, Lijie Tang, Yijing Li, Li Wang, Yigang Xu
Clostridium perfringens α-toxin is one of the major virulence factors during C. perfringens infection, causing hemolysis of erythrocytes in various species. Here, genetically engineered Lactobacillus casei (pPG-α/L. casei 393) constitutively expressing the toxoid of C. perfringens α-toxin was generated and its immunogenicity in mice for induction of protective immunity against the α-toxin was evaluated via oral immunization. The α-toxoid was constitutively expressed by pPG-α/L. casei 393 without a specific inducer, as confirmed by western blotting, laser confocal microscopy, and flow cytometry...
February 26, 2019: Virulence
Hüseyin Sancar Bozkurt, Eamonn Mm Quigley, Banu Kara
Colorectal cancer is the third most common cancer and the third leading cause of cancer-related death. The pathogensesis of colorectal cancer involves a multi-step and multi-factorial process. Disruption of the gut microbiota has been associated with gastrointestinal diseases such as colorectal cancer. The genus Bifidobacterium is considered an important component of the commensal microbiota and plays important roles in several homeostatic functions: immune, neurohormonal, and metabolic. Bifidobacterium animalis subsp...
2019: SAGE Open Medicine
Scott N Dean, Dagmar H Leary, Claretta J Sullivan, Eunkeu Oh, Scott A Walper
Bacterial membrane vesicles have been implicated in a broad range of functions in microbial communities from pathogenesis to gene transfer. Though first thought to be a phenomenon associated with Gram-negative bacteria, vesicle production in Staphylococcus aureus, Lactobacillus plantarum, and other Gram-positives has recently been described. Given that many Lactobacillus species are Generally Regarded as Safe and often employed as probiotics, the engineering of Lactobacillus membrane vesicles presents a new avenue for the development of therapeutics and vaccines...
January 29, 2019: Scientific Reports
Laura M Alexander, Jee-Hwan Oh, Donald S Stapleton, Kathryn L Schueler, Mark P Keller, Alan D Attie, Jan-Peter van Pijkeren
Lactobacillus reuteri has the potential to be developed as a microbial therapeutic delivery platform because of an established safety profile, health-promoting properties, and available genome editing tools. Here, we showed that L. reuteri VPL1014 exhibits a low mutation rate compared to other gram-positive bacteria, which we expect will contribute to the stability of genetically modified strains. VPL1014 encodes two biologically active prophages, which are induced during GI transit. We hypothesized that intracellular accumulated recombinant protein can be delivered in situ following bacteriophage-mediated lysis...
January 25, 2019: Applied and Environmental Microbiology
Chandradhish Ghosh, Paramita Sarkar, Rahaf Issa, Jayanta Haldar
As more antibiotics are rendered ineffective by drug-resistant bacteria, focus must be shifted towards alternative therapies for treating infections. Although several alternatives already exist in nature, the challenge is to implement them in clinical use. Advancements within biotechnology, genetic engineering, and synthetic chemistry have opened up new avenues towards the search for therapies that can substitute for antibiotics. This review provides an introduction to the various promising approaches that have been adopted in this regard...
January 22, 2019: Trends in Microbiology
Eun Ju Yun, Jingjing Liu, Jaewon Lee, Suryang Kwak, Sora Yu, Kyoung Heon Kim, Yong-Su Jin
Fucosyl-oligosaccharides (FOSs) play physiologically important roles as prebiotics, neuronal growth factors, and inhibitors of enteropathogens. However, challenges in designed synthesis and mass production of FOSs hamper their industrial applications. Here, we report flexible biosynthetic routes to produce various FOSs, including unnatural ones, through in vitro enzymatic reactions of various sugar acceptors, such as glucose, cellobiose, and agarobiose, and GDP-L-fucose as the fucose donor by using α1,2-fucosyltransferase (FucT2)...
January 22, 2019: ACS Synthetic Biology
Chelsea Virgile, Pricila Hauk, Hsuan-Chen Wu, William E Bentley
In addition to engineering new pathways for synthesis, synthetic biologists rewire cells to carry out 'programmable' functions, an example being the creation of wound-healing probiotics. Engineering regulatory circuits and synthetic machinery, however, can be deleterious to cell function, particularly if the 'metabolic burden' is significant. Here, a synthetic regulatory circuit previously constructed to direct E. coli to swim towards hydrogen peroxide, a signal of wound generation, was shown to work even with co-expression of antibiotic resistance genes and genes associated with lactose utilization...
January 21, 2019: Biotechnology Progress
Caroline B Kurtz, Yves A Millet, Marja K Puurunen, Mylène Perreault, Mark R Charbonneau, Vincent M Isabella, Jonathan W Kotula, Eugene Antipov, Yossi Dagon, William S Denney, David A Wagner, Kip A West, Andrew J Degar, Aoife M Brennan, Paul F Miller
The intestine is a major source of systemic ammonia (NH3 ); thus, capturing part of gut NH3 may mitigate disease symptoms in conditions of hyperammonemia such as urea cycle disorders and hepatic encephalopathy. As an approach to the lowering of blood ammonia arising from the intestine, we engineered the orally delivered probiotic Escherichia coli Nissle 1917 to create strain SYNB1020 that converts NH3 to l-arginine (l-arg). We up-regulated arginine biosynthesis in SYNB1020 by deleting a negative regulator of l-arg biosynthesis and inserting a feedback-resistant l-arg biosynthetic enzyme...
January 16, 2019: Science Translational Medicine
Prakash M Halami
Probiotic bacteria with antibacterial activity is of desirable trait since they can check the growth of pathogenic bacteria besides exhibiting health benefits to host. Aim of this study was to characterize Bacillus licheniformis MCC 2512T (MCC 2512), a potential probiotic culture for its ability to produce subtilin-like antibiotics. The anti-microbial compound produced by MCC 2512 was identified and characterized using subtilin-specific cell reporter, Bacillus subtilis 168:BS2 (BS2). Induction of β-gal by the test culture suggested the ability of B...
December 27, 2018: Microbial Pathogenesis
Maryam Eshrati, Federico Amadei, Simone Staffer, Wolfgang Stremmel, Motomu Tanaka
The oral uptake of probiotic microorganisms as food additives is one widely taken strategy to sustain and improve the homeostasis of intestinal microbiota that protect the intestinal epithelia from the attack of pathogenic bacteria. Once delivered to ileum and colon, probiotics must adhere and form colonies on mucus that coats the surface of intestinal epithelial cells. Although an increasing amount of knowledge about the genetic and molecular level mechanisms of probiotics-mucus interactions has been accumulated, little is known about the physicochemical aspects of probiotics-mucus interactions under physiological shear in intestines...
December 19, 2018: Langmuir: the ACS Journal of Surfaces and Colloids
Yong Jun Goh, Rodolphe Barrangou
Our evolving understanding on the mechanisms underlying the health-promoting attributes of probiotic lactobacilli, together with an expanding genome editing toolbox have made this genus an ideal chassis for the development of living therapeutics. The rising adoption of CRISPR-based technologies for prokaryotic engineering has demonstrated precise, efficient and scalable genome editing and tunable transcriptional regulation that can be translated into next-generation development of probiotic lactobacilli with enhanced robustness and designer functionalities...
December 6, 2018: Current Opinion in Biotechnology
Min Ju Park, Myeong Soo Park, Geun Eog Ji
Bifidobacteria are representative probiotics which are defined as live microorganisms that confer a health benefit on the host. Because of their safety and healthfulness when applied to humans, bifidobacteria are suitable as genetically engineered bacteria for applications to benefit human physiology and pathology. However, molecular biological studies of bifidobacteria have been limited due to insufficient genetic tools including effective transformation methods. The aim of this study is to improve the electroporation-mediated transformation efficiency of bifidobacteria to a reproducibly high level...
December 4, 2018: Journal of Microbiological Methods
C Panebianco, F Bou Nasser Eddine, G Forlani, G Palmieri, L Tatangelo, A Villani, L Xu, R Accolla, V Pazienza
The incidence of asthma and allergic diseases of the airways is constantly increasing, both in the industrialised and developing countries, due to harmful and excessive quantities of air pollution. Although some studies have shown an effect of dietary supplementation of specific nutrients (especially with anti-oxidant and anti-inflammatory properties) in reducing airways inflammatory response, the results are not yet conclusive and the science is still at its infancy. Our hypothesis is that combining such nutrients could provide more benefits than using them alone...
December 10, 2018: Beneficial Microbes
Massimo Maddaloni, Irina Kochetkova, Carol Hoffman, David W Pascual
IL-35, a relatively newly discovered cytokine belonging to the larger IL-12 family, shows unique anti-inflammatory properties, believed to be associated with dedicated receptors and signaling pathways. IL-35 plays a pivotal role in the development and the function of both regulatory B (Bregs) and T cells (Tregs). In order to further its therapeutic potential, a dairy Lactococcus lactis strain was engineered to express murine IL-35 (LL-IL35), and this recombinant strain was applied to suppress collagen-induced arthritis (CIA)...
2018: Frontiers in Immunology
Amir Sheikhi, Joel Hayashi, James Eichenbaum, Mark Gutin, Nicole Kuntjoro, Danial Khorsandi, Ali Khademhosseini
The recent decade has witnessed a growing demand to substitute synthetic materials with naturally-derived platforms for minimizing their undesirable footprints in biomedicine, environment, and ecosystems. Among the natural materials, cellulose, the most abundant biopolymer in the world with key properties, such as biocompatibility, biorenewability, and sustainability has drawn significant attention. The hierarchical structure of cellulose fibers, one of the main constituents of plant cell walls, has been nanoengineered and broken down to nanoscale building blocks, providing an infrastructure for nanomedicine...
November 27, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Cédric M Vogt, Monika Hilbe, Mathias Ackermann, Claudio Aguilar, Catherine Eichwald
BACKGROUND: We previously engineered Bacillus subtilis to express an antigen of interest fused to TasA in a biofilm. B. subtilis has several properties such as sporulation, biofilm formation and probiotic ability that were used for the oral application of recombinant spores harboring Echinococcus granulosus paramyosin and tropomyosin immunogenic peptides that resulted in the elicitation of a specific humoral immune response in a dog model. RESULTS: In order to advance our understanding of the research in oral immunization practices using recombinant B...
November 26, 2018: Microbial Cell Factories
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