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Engineered probiotics

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 L. rhamnosus GG and L. rhamnosus GR-1 for gastrointestinal and vaginal mucosal delivery, respectively. Hereto, 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 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
Mark Mimee, Phillip Nadeau, Alison Hayward, Sean Carim, Sarah Flanagan, Logan Jerger, Joy Collins, Shane McDonnell, Richard Swartwout, Robert J Citorik, Vladimir Bulović, Robert Langer, Giovanni Traverso, Anantha P Chandrakasan, Timothy K Lu
Biomolecular monitoring in the gastrointestinal tract could offer rapid, precise disease detection and management but is impeded by access to the remote and complex environment. Here, we present an ingestible micro-bio-electronic device (IMBED) for in situ biomolecular detection based on environmentally resilient biosensor bacteria and miniaturized luminescence readout electronics that wirelessly communicate with an external device. As a proof of concept, we engineer heme-sensitive probiotic biosensors and demonstrate accurate diagnosis of gastrointestinal bleeding in swine...
May 25, 2018: Science
Chelsea Virgile, Pricila Hauk, Hsuan-Chen Wu, Wu Shang, Chen-Yu Tsao, Gregory F Payne, William E Bentley
Synthetic biologists construct innovative genetic/biological systems to treat environmental, energy, and health problems. Many systems employ rewired cells for non-native product synthesis, while a few have employed the rewired cells as 'smart' devices with programmable function. Building on the latter, we developed a genetic construct to control and direct bacterial motility towards hydrogen peroxide, one of the body's immune response signaling molecules. A motivation for this work is the creation of cells that can target and autonomously treat disease, the latter signaled by hydrogen peroxide release...
2018: PloS One
Ming-Hsuan Lee, Jinn-Jy Lin, Yu-Ju Lin, Jui-Jen Chang, Huei-Mien Ke, Wen-Lang Fan, Tzi-Yuan Wang, Wen-Hsiung Li
Kluyveromyces marxianus, a probiotic yeast, is important in industrial applications because it has a broad substrate spectrum, a rapid growth rate and high thermotolerance. To date, however, there has been little effort in its genetic engineering by the CRISPR/Cas9 system. Therefore, we aimed at establishing the CRISPR/Cas9 system in K. marxianus and creating stable haploid strains, which will make genome engineering simpler. First, we predicted the genome-wide target sites of CRISPR/Cas9 that have been conserved among the eight sequenced genomes of K...
May 9, 2018: Scientific Reports
T Gupalova, G Leontieva, T Kramskaya, K Grabovskaya, E Bormotova, D Korjevski, A Suvorov
Streptococcus agalactiae, or group B streptococcus (GBS), is an important pathogen as it is the leading cause of neonatal deaths due to sepsis, meningitis or bacterial pneumonia. Although the development of an effective and safe GBS vaccine is on the agenda of many research labs, there is no GBS vaccine on the market yet. In the present study we attempted to engineer a live vaccine strain based on Bac, a surface protein of GBS, incorporated into a surface fimbrial protein of probiotic Enterococcus. The resulting strain induced specific systemic and local immune responses in mice and provided protection against GBS when administered via the intranasal, oral or intravaginal immunization routes...
2018: PloS One
Katrine L Whiteson
I imagine a future in which children grow up with healthy microbial communities. Engineering human microbiomes might actually be achievable in the near future, as we enter an era of hunting for human-adapted bacterial strains and phages. Furthermore, breath metabolites could allow us to track whether a probiotic colonizes persistently or a phage has knocked down a microbe of interest. Recent successes with probiotics, such as bifidobacteria that can break down human milk oligosaccharides, are making a future in which infants are intentionally colonized with health-promoting strains seem less unlikely...
March 2018: MSystems
David Lubkowicz, Chun Loong Ho, In Young Hwang, Wen Shan Yew, Yung Seng Lee, Matthew Wook Chang
Gram-positive Staphylococcus aureus infection that results in pneumonia, urinary tract infection, and in severe cases, sepsis, has recently been classified as a serious threat to public health. Rapid and cost-effective detection of these infections are costly and time-consuming. Here, we present probiotic lactic acid bacteria engineered to detect autoinducer peptide-I (AIP-I), a quorum sensing molecule produced by Staphylococcus sp. during pathogenesis. We achieved this by adapting the well-characterized agr quorum sensing ( agrQS) from Staphylococcus aureus into Lactobacillus reuteri...
May 18, 2018: ACS Synthetic Biology
Cheng-En Dai, Hai-Long Li, Xiao-Ping He, Fen-Fen Zheng, Hua-Liu Zhu, Liang-Feng Liu, Wei Du
The pharmacological activity of active ingredients from Chinese medicine depends greatly on the microecological environment of probiotics in the human body. After effective ingredients from traditional Chinese medicines are metabolized or biotransformed by probiotics, their metabolites can increase pharmacological activity, and can be absorbed more easily to improve the bioavailability. Therefore, the combination of Chinese medicines with probiotics is the innovation point in R&D of functional food and Chinese medicines, and also a new thinking for the modernization of Chinese medicine...
January 2018: Zhongguo Zhong Yao za Zhi, Zhongguo Zhongyao Zazhi, China Journal of Chinese Materia Medica
Zachary Js Mays, Nikhil U Nair
The trillions of microbes hosted by humans can dictate health or illness depending on a multitude of genetic, environmental, and lifestyle factors that help define the human ecosystem. As the human microbiota is characterized, so can the interconnectivity of microbe-host-disease be realized and manipulated. Designing microbes as therapeutic agents can not only enable targeted drug delivery but also restore homeostasis within a perturbed microbial community. Used for centuries in fermentation and preservation of food, lactic acid bacteria (LAB) have a long history of safe, and occasionally health promoting, interactions with the human gut, making them ideal candidates for engineered functionality...
October 2018: Current Opinion in Biotechnology
Chengchao Ding, Junfei Ma, Qingli Dong, Qing Liu
Live bacteria, including attenuated bacteria and probiotics, can be engineered to deliver target antigen to excite the host immune system. The preponderance of these live bacterial vaccine vectors is that they can stimulate durable humoral and cellular immunity. Moreover, delivery strategies of heterologous antigen in live bacterial promote the applications of new vaccine development. Genetic technologies are evolving, which potentiate the developing of heterologous antigen delivery systems, including bacterial surface display system, bacterial secretion system and balanced lethal vector system...
May 2018: Immunology Letters
Josef R Bober, Chase L Beisel, Nikhil U Nair
An increasing number of studies have strongly correlated the composition of the human microbiota with many human health conditions and, in several cases, have shown that manipulating the microbiota directly affects health. These insights have generated significant interest in engineering indigenous microbiota community members and nonresident probiotic bacteria as biotic diagnostics and therapeutics that can probe and improve human health. In this review, we discuss recent advances in synthetic biology to engineer commensal and probiotic lactic acid bacteria, bifidobacteria, and Bacteroides for these purposes, and we provide our perspective on the future potential of these technologies...
June 4, 2018: Annual Review of Biomedical Engineering
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