Bioengineering a non-pathogenic bacteria to produce medically-relevant biopolymers

对非致病性细菌进行生物工程以生产医学相关的生物聚合物

• 批准号: 8977656
• 负责人: Richard M. Niles
• 金额: $ 14.4万
• 依托单位: PROGENESIS TECHNOLOGIES, LLC
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-07 至 2017-02-06
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8977656
• 关键词: Acetylation; Aerobic Bacteria; Alginates; Animal Experimentation; Azotobacter; Bacteria; Biomedical Engineering; Biopolymers; Caring; Characteristics; Chemicals; Consultations; Data; Delayed-Action Preparations; Development; Drug Delivery Systems; Endotoxins; Engineering; Environment; Escherichia coli; Excipients; Exotoxins; Fermentation; Food; Food Additives; Genes; Genetic Engineering; Goals; Grant; Growth; Harvest; Lead; Legal patent; Letters; Licensing; Lipopolysaccharides; Marketing; Medical; Methods; Modeling; Mus; Nutritional Requirements; O Antigens; Pathogenicity; Patients; Performance; Pharmaceutical Cares; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phospholipase C; Plants; Process; Production; Property; Pseudomonas; Pseudomonas aeruginosa; Public Health; Pyocyanine; Recombinants; Recovery; Relative (related person); Research; Seaweed; Side; Small Business Innovation Research Grant; Structure; Technology; Textiles; United States; United States Food and Drug Administration; Virulence Factors; Waste Products; Water; West Virginia; Work; absorption; antimicrobial; care delivery; commercialization; cost; design; expression vector; interest; large scale production; manufacturing facility; mouse model; product development; public health relevance; remediation; scale up; wasting; wound

 DESCRIPTION (provided by applicant): Alginate is a commercially-viable anionic biopolymer consisting of two monomeric subunits, ß-D-mannuronate and a-L-guluronate. Alginate is used in a variety of applications including textile manufacturing, waste water remediation food production, and a variety of medical applications such as wound care and drug delivery. Currently, commercial alginate is harvested from various genera of brown seaweeds. However, seaweed- derived alginate has several limitations including: seasonal growth, inconsistencies in yield, composition and quality between harvests, supply-side instability and the use of economically and environmentally costly processing methods. These limitations impact seaweed-derived alginate's use for biomedical and pharmaceutical application. Alginate is also produced by bacteria in the genera Azotobacter and Pseudomonas. Moreover, bacteria-derived alginate has several advantages; specifically, it is relatively easy, inexpensive, and environmentally-friendly to cultivate and harvest. Additionally, the bacteria can be easily manipulated to produce large amounts of alginate with specific customized properties for biomedical and pharmaceutical applications. However, there is little ongoing research to develop bacterial strains for commercial alginate production. Progenesis Technologies, LLC has patented a stable high alginate producing strain of Pseudomonas aeruginosa for use in recombinant alginate production. At a pre-petition consultation, the United States Federal Drug Administration (FDA) suggested abrogating the function of the secreted virulence factors exotoxin A and pyocyanin to decrease the relative pathogenicity of VE2. The FDA also suggested using the currently approved bacterial strains for alginate production. To date, we have abrogated the function of the virulence factors exotoxin A, pyocyanin, phospholipase C and endotoxin. In this proposal, we intended to design and evaluate a non- pathogenic bacterial strain for the production of the biopolymer alginate. We propose to accomplish this through the completion of two Specific Aims. In Aim 1, we will evaluate the pathogenicity of our recently modified P. aeruginosa strain PGN4 using a murine model. In Aim 2, we will determine the feasibility of producing alginate using currently approved E. coli strains. At the conclusion of ths project, we will seek the appropriate federal approval to use our newly-acquired, non-pathogenic bacterial strain as a platform for the production of biomedical and pharmaceutical grade alginate for use in various medical applications.

 描述（通过应用程序提供）：藻酸盐是一种在商业上可行的阴离子生物聚合物，由两个单体亚基组成，ß-d-甘露酸酯和a-l-guluronate。藻酸盐用于多种应用，包括纺织品制造，废水补救食品生产以及各种医疗应用，例如伤口护理和药物输送。目前，商业藻酸盐是从各种棕色海藻属收获的。但是，海藻衍生的藻酸盐具有多个局限性，包括：季节性增长，收益率不一致，收获之间的成分和质量，供应方不稳定性以及经济和环境上昂贵的加工方法的使用。这些限制会影响海藻衍生的藻酸盐用于生物医学和药物应用。藻酸盐也由抗二杆菌和假单胞菌属中的细菌产生。此外，细菌衍生的藻酸盐具有多个优点。具体而言，耕种和收获相对容易，便宜且环保。此外，可以轻松地操纵细菌，以产生大量算法，并具有特定的定制特性用于生物医学和药物应用。但是，几乎没有正在进行的研究来开发用于商业藻酸盐生产的细菌菌株。祖发技术有限责任公司已为铜绿假单胞菌的稳定高藻酸盐生产菌株提供专利，用于重组藻酸盐生产。在请愿前咨询中，美国联邦药物管理局（FDA）提出分泌病毒因子Exotoxin A和pyocyanin的功能，以降低VE2的相对致病性。 FDA还建议使用当前批准的细菌菌株进行藻酸盐产生。迄今为止，我们已经催化了病毒因子Exotoxin A，增值苷，磷脂酶C和内毒素的功能。在此提案中，我们打算设计和评估非致病细菌菌株以生产生物聚合物藻酸盐。我们建议通过完成两个具体目标来实现这一目标。在AIM 1中，我们将使用鼠模型评估我们最近修饰的铜绿假单胞菌菌株PGN4的致病性。在AIM 2中，我们将使用当前批准的大肠杆菌菌株确定生产算法的可行性。在THS项目结束时，我们将寻求适当的联邦批准，以使用我们新获得的非致病细菌菌株作为生产生物医学和药品级算法的平台，用于在各种医疗应用中使用。

项目成果

Presence of Segmented Filamentous Bacteria in Human Children and Its Potential Role in the Modulation of Human Gut Immunity.

• DOI: 10.3389/fmicb.2018.01403
• 发表时间: 2018
• 期刊: Frontiers in microbiology
• 影响因子: 5.2
• 作者: Chen B;Chen H;Shu X;Yin Y;Li J;Qin J;Chen L;Peng K;Xu F;Gu W;Zhao H;Jiang L;Li L;Song J;Elitsur Y;Yu HD;Jiang M;Wang X;Xiang C
• 通讯作者: Xiang C