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)

• 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
• 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

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（由申请方提供）：细菌干扰在肠道细菌和致病菌种之间产生生态竞争。与成熟果实中通过发酵的微生物竞争一样，在成熟果实中已经发现了通过发酵的细菌干扰。 深层的皮肤吸收了厌氧微环境，允许细菌将碳水化合物发酵成短链脂肪酸（SCFA）。酸奶是用对肠道友好的细菌发酵的牛奶，是平衡人体肠道细菌生态系统的极好辅助物。先前的研究表明，皮肤中的SCFAs在影响细菌在正常人皮肤上的主要居住方面起着重要作用。因此，我们假设人类皮肤细菌的发酵产物，如通过友好肠道细菌发酵制成的酸奶，可以作为皮肤益生菌用于治疗病原体引起的皮肤感染。在这项提案中，我们将使用皮肤微生物组中的细菌发酵作为益生菌（Bfismp）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，因此开发有效的MRSA治疗药物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细菌，占皮肤微生物总数的50%以上。痤疮丙酸杆菌因其将碳水化合物发酵成丙酸的能力而得名。我们的初步结果表明，丙酸有效地抑制生长的USA 300，社区获得性MRSA，在体外和体内。更有趣的是，我们还证明了痤疮丙酸杆菌的发酵培养基（作为Bfismp）对USA 300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对付S。金黄色葡萄球菌/MRSA感染，建立Bfismp中SCFA谱，并检测抗-S. 2）探讨Bfismp降低S. aureus/MRSA细胞内pH的作用机制。金黄色葡萄球菌/MRSA的皮肤感染，并验证Bfismp在体内抑制S.金黄色葡萄球菌/MRSA;和3）确定皮肤细胞对Bfismp的反应，并测试由局部应用Bfismp引起的可能的副作用。STTR第一阶段项目将在加州大学圣地亚哥分校和Surface Bioadvances Inc.合作的基础上进行，一家圣地亚哥公司，其商业目标是开发针对传染病的疗法。我们已经形成了一个坚实的研究团队，包括皮肤细菌学家（黄博士; PI在加州大学圣地亚哥分校），分子生物学家（蒋博士在表面生物进步公司），皮肤科医生（Gallo博士）和微生物学家（Nizet博士）。如果成功，来自皮肤真菌发酵的杀菌剂将使美国每年超过126，000名MRSA感染患者的整个社区受益。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

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: 10.3390/ijms19051290
• 发表时间: 2018
• 期刊: International journal of molecular sciences
• 影响因子: 5.6
• 作者: Yang,John-Jackson;Chang,Ting-Wei;Jiang,Yong;Kao,Hsin-Jou;Chiou,Bin-Hao;Kao,Ming-Shan;Huang,Chun-Ming
• 通讯作者: Huang,Chun-Ming