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Engineered probiotics

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
Kandasamy Saravanakumar, Davoodbasha Mubarak Ali, Kandasamy Kathiresan, Myeong-Hyeon Wang
Biopolymers are ubiquitous in biomedical and healthcare application. Its nanocomposites have gained the more attention as antimicrobials, drug carrier, sensors, disease diagnosis, tissue engineering, wound healing and cancer therapy. These biopolymer composites are efficient in holding, protect and releasing the bioactive drugs such as pharmaceutics, nutraceuticals, enzymes and probiotics. Several studies are revealed that polymer based drug delivery system in cancer therapy and microbial treatments so on. However, this mini review emphasized the source, extraction, and characterizations of the biopolymers and their use in the fabrication of various drug or metals based nanocomposites followed by its utilization as drug carrier or drug to treat the various diseases such as antimicrobial infections and cancer...
November 20, 2018: Current Pharmaceutical Design
Ruijuan Li, Linda Helbig, Jun Fu, Xiaoying Bian, Jennifer Herrmann, Michael Baumann, A Francis Stewart, Rolf Müller, Aiying Li, Daniel Zips, Youming Zhang
Abnormal blood vessels and hypoxic and necrotic regions are common features of solid tumors and related to the malignant phenotype and therapy resistance. Certain obligate or facultative anaerobic bacteria exhibit inherent ability to colonize and proliferate within solid tumors in vivo. Escherichia coli Nissle 1917 (EcN), a non-pathogenic probiotic in European markets, has been known to proliferate selectively in the interface between the viable and necrotic regions of solid tumors. The objective of this study was to establish a tumor-targeting therapy system using the genetically engineered EcN for targeted delivery of cytotoxic compounds, including colibactin, glidobactin and luminmide...
November 14, 2018: Research in Microbiology
Mengfei Peng, Zajeba Tabashsum, Puja Patel, Cassandra Bernhardt, Debabrata Biswas
Probiotics, particularly lactic acid bacteria, are biologic agents which limit the growth, virulence, and survival/colonization of various enteric bacterial pathogens and serve as potential alternatives to antibiotics. Mechanisms that contribute to this antimicrobial effect include producing bioactive metabolites/acids, increasing nutrient and receptor-mediated competition, and modulating gut microbiome ecology. However, these functions of common probiotic strains are limited due to the finite quantity of metabolites they produce and their total number in the gut ecosystem...
2018: Frontiers in Microbiology
Wenye Xu, Peizhu Su, Lijun Zheng, Hongying Fan, Ye Wang, Yangyang Liu, Yuqing Lin, Fachao Zhi
Non-toxigenic Bacteroides fragilis is regarded as a potential candidate for probiotic owing to its various advantages. We previously isolated a new strain of B. fragilis (ZY-312) and verified its biosafety and capability of inhibiting the growth of pathogens in vivo . However, the colonization of ZY-312 in gastrointestinal (GI) tract remains to be determined. To track the colonization of ZY-312, mice were gavaged with ZY-312 labeled by means of metabolic oligosaccharide engineering and bioorthogonal click chemistry or given AF647-dibenzocyclooctyne (DIBO) directly...
2018: Frontiers in Microbiology
Svante Twetman
Today, dental caries is regarded as a preventable non-communicable disease (NCD) that affects a majority of the population across their lifespan. As such, it shares a number of behavioural, socio-economic, and lifestyle factors with other NCDs, such as overweight and diabetes, and should be subjected to a similar model of chronic disease management. Caries prevention has traditionally relied on fluoride exposure, diet control, thorough oral hygiene, and antibacterial measures. Prevention of caries as an NCD does certainly not disqualify these methods, but brings them into a new context...
October 2018: European Journal of Oral Sciences
Rajni Hatti-Kaul, Lu Chen, Tarek Dishisha, Hesham El Enshasy
Lactic acid bacteria constitute a diverse group of industrially significant, safe microorganisms that are primarily used as starter cultures and probiotics, and are also being developed as production systems in industrial biotechnology for biocatalysis and transformation of renewable feedstocks to commodity- and high value chemicals, and health products. Development of strains, which was initially based mainly on natural approaches, is also achieved by metabolic engineering that has been facilitated by the availability of genome sequences and genetic tools for transformation of some of the bacterial strains...
August 30, 2018: FEMS Microbiology Letters
Peter A Bron, Michiel Kleerebezem
Food-grade lactic acid bacteria (LAB) are considered suitable vehicles for the production and/or delivery of health promoting or therapeutic, bioactive molecules. The molecules considered for health-beneficial use include the endogenous effector molecules produced by probiotics (mostly lactobacilli), as well as heterologous bioactives that can be produced in LAB by genetic engineering (mostly using lactococci). Both strategies aim to deliver appropriate dosages of specific bioactive molecules to the site of action...
2018: Frontiers in Microbiology
Karla J F Satchell
Over 1.3 billion persons are at risk for cholera globally. Vaccination campaigns are growing, but intervention options providing nearly immediate protection are also needed. Two recent papers in Science Translational Medicine describe probiotic bacteria that reduce intestinal colonization in animal models and show promise for development as prophylaxis agents.
August 8, 2018: Cell Host & Microbe
Patrick H Bradley, Stephen Nayfach, Katherine S Pollard
The mechanisms by which different microbes colonize the healthy human gut versus other body sites, the gut in disease states, or other environments remain largely unknown. Identifying microbial genes influencing fitness in the gut could lead to new ways to engineer probiotics or disrupt pathogenesis. We approach this problem by measuring the statistical association between a species having a gene and the probability that the species is present in the gut microbiome. The challenge is that closely related species tend to be jointly present or absent in the microbiome and also share many genes, only a subset of which are involved in gut adaptation...
August 2018: PLoS Computational Biology
Sebastian Torres, Emanuel Fabersani, Antonela Marquez, Paola Gauffin-Cano
PURPOSE: The first part of this review focuses on the role of cells and molecules of adipose tissue involved in metabolic syndrome-induced inflammation and in the maintenance of this pathology. In the second part of the review, the potential role of probiotics-modulating metabolic syndrome-related inflammatory components is summarized and discussed. METHODS: The search for the current scientific literature was carried out using ScienceDirect, PubMed, and Google Scholar search engines...
July 24, 2018: European Journal of Nutrition
Mariya I Petrova, Marianne F L van den Broek, Irina Spacova, Tine L A Verhoeven, Jan Balzarini, Jos Vanderleyden, Dominique Schols, Sarah Lebeer
Probiotic bacteria are being explored for the in situ delivery of various therapeutic agents. In this study, we aimed to express two HIV-inhibiting lectins, actinohivin (AH) and griffithsin (GRFT), in the probiotic strains Lactobacillus rhamnosus GG and L. rhamnosus GR-1 for gastrointestinal and vaginal mucosal delivery, respectively. Constructs were generated for the intracellular and extracellular production of AH and GRFT under the control of the promoter of their Major Secreted Protein Msp1. Also, intracellular expression of GRFT was investigated under the control of the nisA promoter from the inducible nisin-controlled expression (NICE) system...
July 21, 2018: International Journal of Antimicrobial Agents
Han Zhou, Xuechun Li, Zongying Wang, Jiyuan Yin, Hongchao Tan, Li Wang, Xinyuan Qiao, Yanping Jiang, Wen Cui, Min Liu, Yijing Li, Yigang Xu, Lijie Tang
BACKGROUND: Lactobacillus casei (L. casei) is well known for its probiotic property in human and animals. Lactoferricin (Lfcin) polypeptide can effectively modulate host immune responses and have antimicrobial activity in vivo and in vitro. In order to develop a food-grade L. casei system constitutively expressing bovine Lfcin, this study constructed a thymidine auxotrophy (ΔthyA) recombinant L. casei. RESULTS: Based on the thymidylate synthase gene (thyA) insert site, LFEC(Lfcin expression cassette)was inserted into L...
June 27, 2018: BMC Veterinary Research
Ning Mao, Andres Cubillos-Ruiz, D Ewen Cameron, James J Collins
Microbiota-modulating interventions are an emerging strategy to promote gastrointestinal homeostasis. Yet, their use in the detection, prevention, and treatment of acute infections remains underexplored. We report the basis of a probiotic-based strategy to promote colonization resistance and point-of-need diagnosis of cholera, an acute diarrheal disease caused by the pathogen Vibrio cholerae Oral administration of Lactococcus lactis , a common dietary fermentative bacterium, reduced intestinal V. cholerae burden and improved survival in infected infant mice through the production of lactic acid...
June 13, 2018: Science Translational Medicine
N G Kapse, A S Engineer, V Gowdaman, S Wagh, P K Dhakephalkar
Spore forming Bacillus species are widely used as probiotics for human dietary supplements and in animal feeds. However, information on genetic basis of their probiotic action is obscure. Therefore, the present investigation was undertaken to elucidate probiotic traits of B. coagulans HS243 through its genome analysis. Genome mining revealed the presence of an arsenal of marker genes attributed to genuine probiotic traits. In silico analysis of HS243 genome revealed the presence of multi subunit ATPases, ADI pathway genes, chologlycine hydrolase, adhesion proteins for surviving and colonizing harsh gastric transit...
May 30, 2018: Genomics
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