Bacterial fermentation in skin microbiome as probiotics (Bfismp) against S. aureu

皮肤微生物组中的细菌发酵作为对抗金黄色葡萄球菌的益生菌 (Bfismp)

基本信息

批准号：
8452574
负责人：
CHUN-MING HUANG
金额：
$ 15万
依托单位：
SURFACE BIOADVANCES, INC.
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-05 至 2015-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8452574
关键词：
Abscess Accounting Acetates Adverse effects Antibiotic Resistance Antibiotics Back Bacteria Bacterial Infections Bacterial Interference Businesses California Carbohydrates Cells Centers for Disease Control and Prevention (U.S.)Cessation of life Clinic Collaborations Communicable Diseases Communities Community-Acquired Infections Consumption Dermatologist Development Ecosystem Equilibrium Family Fermentation Fruit Gland Gram-Positive Bacteria Growth HIV Health Hospitalization Hospitals Human Human body In Vitro Individual Industry Infection Infectious Skin Diseases Intestines Invaded Medicine Microbe Milk Modality Molecular Names Organ Organ failure Outpatients Patients Phase Play Prevention Probiotics Propionibacterium acnes Propionic Acids Pus Recurrence Reporting Research Resistance Role Sales Skin Skin Care Skin Tissue Small Business Technology Transfer Research Soft Tissue Infections Solid Staphylococcal Infections Staphylococcus aureus Staphylococcus epidermidis Starch Surface Sweat Sweating Systemic infection Testing Therapeutic Time Topical application United States Universities Visit Volatile Fatty Acids Yogurt bactericide base commensal microbes density fighting gastrointestinal system in vivo methicillin resistant Staphylococcus aureus microbial microbiome microorganism novel pathogen prevent public health relevance residence response skin abscess skin lesion sugar wound

项目摘要

DESCRIPTION (provided by applicant): Bacterial interference creates an ecological competition between commensal bacteria and pathogenic species. Like microbial competition via fermentation in a ripening fruit, bacterial interference via fermentation has been found in the deep-seated skin abscesses where is an anaerobic microenvironment, allowing bacteria to ferment carbohydrates to short-chain fatty acids (SCFA). Fermentation of milk with gut- friendly bacteria, yogurt is an excellent aid to balance the bacteriological ecosystem in the human intestine. Previous studies indicated that SCFAs in skin played a curial role in influencing the predominant residence of bacteria on normal human skin. Thus, we hypothesize that fermentation products of human skin commensal bacteria, like yogurt made by fermentation with friendly gut bacteria, can function as skin probiotics for treatment of skin infections by pathogens. In this proposal, we will use the bacterial fermentation in skin microbiome as probiotics (Bfismp) against methicillin-resistant Staphylococcus aureus (MRSA). It remains as an unmet challenge to develop effective therapeutics for MRSA treatment because of its formidable resistance against multiple traditional antibiotics. Everyone carried Propionibacterium acnes (P. acnes), a Gram-positive and skin commensal bacterium accounting for more than 50% of the total skin microbiome. P. acnes was named for its ability to ferment carbohydrates to propionic acid. Our preliminary results have demonstrated that propionic acid effectively suppressed the growth of USA300, a community-acquired MRSA, both in vitro and in vivo. More intriguingly, we also demonstrated that fermented media (acted as Bfismp) of P. acnes exerted an inhibitory effect on the growth of USA300. Three Specific Aims we proposed are to 1) Use the Bfismp against S. aureus/MRSA infection, establish the profiles of SCFA in Bfismp, and examine the anti-S. aureus/MRSA activity of Bfismp in vitro; 2) Explore the action mechanism of Bfismp on decreasing the intracellular pH of S. aureus/MRSA, and validate the in vivo potency of Bfismp in inhibiting skin infection of S. aureus/MRSA; and 3) Determine the response of skin cells to Bfismp, and test the possible side effects caused by topical application of Bfismp. The STTR Phase I project will be conducted based on collaboration between University of California, San Diego and Surface Bioadvances Inc., a San Diego company with a business aim to develop therapeutics against infectious diseases. We have formed a solid research team consisting of a skin bacteriologist (Dr. Huang; PI at UCSD), a molecular biologist (Dr. Jiang at Surface Bioadvances Inc.), a dermatologist (Dr. Gallo), and microbiologist (Dr. Nizet). When successful, bactericides derived from fermentation of skin commensal bacteria will benefit the entire community of patients with MRSA infections consisting of over 126,000 patients per year in United States. The impact of this proposal includes opening a novel skin-care industry of using Bfismp for treating skin infection and/or promoting skin health.

描述（由申请人提供）：细菌干扰造成共生细菌和病原菌之间的生态竞争。就像成熟水果中通过发酵进行的微生物竞争一样，在水果中也发现了通过发酵进行的细菌干扰。深层皮肤脓肿存在厌氧微环境，允许细菌将碳水化合物发酵为短链脂肪酸 (SCFA)。酸奶用肠道友好的细菌发酵牛奶，是平衡人体肠道细菌生态系统的极好帮助。先前的研究表明，皮肤中的 SCFA 在影响细菌在正常人体皮肤上的主要驻留方面发挥着重要作用。因此，我们假设人类皮肤共生细菌的发酵产物，例如用友好的肠道细菌发酵制成的酸奶，可以作为皮肤益生菌来治疗病原体引起的皮肤感染。在该提案中，我们将利用皮肤微生物群中的细菌发酵作为益生菌（Bfismp）来对抗耐甲氧西林金黄色葡萄球菌（MRSA）。由于 MRSA 对多种传统抗生素具有强大的耐药性，开发有效的 MRSA 治疗方法仍然是一个尚未解决的挑战。每个人都携带痤疮丙酸杆菌 (P. acnes)，这是一种革兰氏阳性皮肤共生细菌，占皮肤微生物群总数的 50% 以上。痤疮丙酸杆菌因其能够将碳水化合物发酵成丙酸而得名。我们的初步结果表明，丙酸在体外和体内均有效抑制了 USA300（一种社区获得性 MRSA）的生长。更有趣的是，我们还证明了痤疮丙酸杆菌的发酵培养基（Bfismp）对 USA300 的生长具有抑制作用。我们提出的三个具体目标是 1) 使用 Bfismp 对抗金黄色葡萄球菌/MRSA 感染，在 Bfismp 中建立 SCFA 谱，并检查抗金黄色葡萄球菌。 Bfismp 体外金黄色葡萄球菌/MRSA 活性； 2）探索Bfismp降低金黄色葡萄球菌/MRSA细胞内pH的作用机制，验证Bfismp体内抑制金黄色葡萄球菌/MRSA皮肤感染的功效； 3）测定皮肤细胞对Bfismp的反应，并测试局部应用Bfismp可能引起的副作用。 STTR 第一阶段项目将基于加州大学圣地亚哥分校和 Surface Bioadvances Inc. 之间的合作进行，Surface Bioadvances Inc. 是一家圣地亚哥公司，其业务目标是开发针对传染病的治疗方法。我们已经组建了一支坚实的研究团队，由皮肤细菌学家（UCSD PI 黄博士）、分子生物学家（Surface Bioadvances Inc. 姜博士）、皮肤科医生（Gallo 博士）和微生物学家（Nizet 博士）组成。）。一旦成功，源自皮肤共生细菌发酵的杀菌剂将使整个 MRSA 感染患者群体受益，美国每年有超过 126,000 名患者。该提案的影响包括开辟一个使用 Bfismp 治疗皮肤感染和/或促进皮肤健康的新型皮肤护理行业。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（2）

5-methyl Furfural Reduces the Production of Malodors by Inhibiting Sodium l-lactate Fermentation of Staphylococcus epidermidis: Implication for Deodorants Targeting the Fermenting Skin Microbiome.

5-甲基糠醛通过抑制表皮葡萄球菌的 L-乳酸钠发酵来减少恶臭的产生：对针对发酵皮肤微生物组的除臭剂的影响。

DOI：
发表时间：
2019-08-05
期刊：
影响因子：
4.5
作者：
Kumar, Manish;Myagmardoloonjin, Binderiya;Keshari, Sunita;Negari, Indira Putri;Huang, Chun
通讯作者：
Huang, Chun

Commensal Staphylococcus aureus Provokes Immunity to Protect against Skin Infection of Methicillin-Resistant Staphylococcus aureus.

共生金黄色葡萄球菌激发免疫力，防止耐甲氧西林金黄色葡萄球菌的皮肤感染。

DOI：
发表时间：
2018-04-25
期刊：
影响因子：
5.6
作者：
Yang, John;Chang, Ting;Jiang, Yong;Kao, Hsin;Chiou, Bin;Kao, Ming;Huang, Chun
通讯作者：
Huang, Chun

A Derivative of Butyric Acid, the Fermentation Metabolite of Staphylococcus epidermidis, Inhibits the Growth of a Staphylococcus aureus Strain Isolated from Atopic Dermatitis Patients.

丁酸衍生物（表皮葡萄球菌的发酵代谢物）可抑制从特应性皮炎患者体内分离出的金黄色葡萄球菌菌株的生长。

DOI：
发表时间：
2019
期刊：
影响因子：
4.2
作者：
Traisaeng, Supitchaya;Herr, Deron Raymond;Kao, Hsin;Chuang, Tsung;Huang, Chun
通讯作者：
Huang, Chun

A Co-Drug of Butyric Acid Derived from Fermentation Metabolites of the Human Skin Microbiome Stimulates Adipogenic Differentiation of Adipose-Derived Stem Cells: Implications in Tissue Augmentation.

源自人类皮肤微生物组发酵代谢物的丁酸联合药物刺激脂肪干细胞的成脂分化：对组织增强的影响。

DOI：
10.1016/j.jid.2016.07.030
发表时间：
2024-09-13
期刊：
The Journal of investigative dermatology
影响因子：
0
作者：
Yanhan Wang;Ling;Jinghua Yu;Stephen Huang;Zhenping Wang;K. Chun;T. L. Lee;Ying
通讯作者：
Ying