THE IMPACT OF LIPID METABOLISM ON STAPHYLOCOCCAL MASTITIS

脂质代谢对葡萄球菌性乳腺炎的影响

• 批准号: 7381183
• 负责人: MARK Adam MCGUIRE
• 金额: $ 28.62万
• 依托单位: UNIVERSITY OF IDAHO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7381183
• 关键词: IMPACT; LIPID; METABOLISM; STAPHYLOCOCCAL; MASTITIS

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Staphylococcus aureus causes a wide variety of diseases in both humans and animals. Although largely unreported, staphylococcal infection of the mammary gland, or mastitis, affects millions of women each year - nearly 33% of nursing mothers. Unfortunately, studies have determined that mastitis in women is a significant cause for the cessation of breast-feeding. This is particularly significant given that the benefits of breast-feeding have now been well documented. For example, these benefits include protection of the infant against diarrheal and respiratory diseases, ultimately leading to a lower risk of postneonatal death. In addition, breast-fed infants exhibit a reduced risk of obesity and cardiovascular disease in adulthood. Perhaps more alarming are studies showing that mastitis in HIV-infected women is a major risk factor in the transmission of this virus from mother to infant. Despite the impact of mastitis on human health, little is known about the host-pathogen interactions that occur with mastitis. Recent studies have demonstrated that the lipids found in milk have profound effects on pathogens such as S. aureus. For example, glycerol monolaurate (GML) has an inhibitory effect on the growth of S. aureus and inhibits the expression of virulence factors in S. aureus at subinhibitory concentrations. The active agent in GML as indicated by our preliminary studies appears to be the free fatty acid, lauric acid. In addition, our studies indicate that other fatty acids commonly found in milk possess antimicrobial activity. Thus, lipids may not just be an energy source for the nursing infant; many fatty acids made available by the action of both bacterial and mammalian lipases may also play a role in minimizing the impact of pathogens on the host through inhibition of bacterial growth and virulence. Therefore, the overall objective of this proposal is to test the hypothesis that specific fatty acids and lipases impact the progression of staphylococcal mastitis. This hypothesis will be tested in three specific aims including: 1) To determine the fatty acids and form of lipid that regulate the growth and expression of virulence factors in S. aureus. In this aim we will determine the range of fatty acids present in milk that affect growth and virulence factor production in S. aureus. 2) To examine the regulation and significance of lipase activity in S. aureus and the mammary gland as a mechanism to provide benefits to the pathogen and/or host. Here, we will study the role of both pathogen- and host-encoded lipases on milk lipid metabolism and determine their potential roles in the progression of disease within mammary tissue. 3) To compare the effects of altered milk lipid composition on the host-pathogen response to an infection with S. aureus. This aim will address the impact of altering the lipid composition of milk, through dietary supplementation, on the resistance and severity of staphylococcal mastitis. The results of these studies will have a major impact on our understanding of the host-pathogen interactions that occur within the mammary gland and could lead to novel strategies to reduce these types of infections in women.

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。金黄色葡萄球菌在人类和动物中都会引起多种疾病。尽管在很大程度上没有报告，但乳腺葡萄球菌感染或乳房炎每年影响数百万妇女--近33%的哺乳母亲。不幸的是，研究已经确定，女性乳房炎是导致停止母乳喂养的重要原因。考虑到母乳喂养的好处现在已经有了很好的记录，这一点尤其重要。例如，这些好处包括保护婴儿免受腹泻和呼吸系统疾病的影响，最终降低新生儿死亡的风险。此外，母乳喂养的婴儿成年后患肥胖症和心血管疾病的风险较低。也许更令人担忧的是，研究表明，艾滋病毒感染妇女的乳房炎是这种病毒从母亲传播给婴儿的主要风险因素。尽管乳房炎对人类健康有影响，但人们对乳房炎发生的宿主-病原体相互作用知之甚少。最近的研究表明，牛奶中发现的脂类对金黄色葡萄球菌等病原体有深远的影响。例如，单月桂酸甘油(GML)对金黄色葡萄球菌的生长有抑制作用，并在亚抑制浓度下抑制金黄色葡萄球菌毒力因子的表达。我们的初步研究表明，GML中的活性物质似乎是游离脂肪酸月桂酸。此外，我们的研究表明，牛奶中常见的其他脂肪酸具有抗菌活性。因此，脂类可能不仅仅是哺乳婴儿的能量来源；通过细菌和哺乳动物脂肪酶的作用而获得的许多脂肪酸也可能通过抑制细菌生长和毒力来最大限度地减少病原体对宿主的影响。因此，这项建议的总体目标是检验特定脂肪酸和脂肪酶影响葡萄球菌性乳房炎进展的假设。这一假说将在三个具体目标上进行检验，包括：1)确定调节金黄色葡萄球菌生长和毒力因子表达的脂肪酸和脂质形式。在这个目标中，我们将确定牛奶中存在的影响金黄色葡萄球菌生长和毒力因子产生的脂肪酸的范围。2)研究金黄色葡萄球菌和乳腺中脂肪酶活性的调节及其意义，以期为病原体和(或)宿主提供帮助。在这里，我们将研究病原体和宿主编码的脂肪酶在乳脂代谢中的作用，并确定它们在乳腺组织内疾病进展中的潜在作用。3)比较乳脂成分改变对金黄色葡萄球菌感染宿主病原菌反应的影响。这一目标将解决通过饮食补充改变牛奶的脂肪成分对葡萄球菌性乳房炎的抵抗力和严重性的影响。这些研究的结果将对我们理解发生在乳腺内的宿主-病原体相互作用产生重大影响，并可能导致减少女性这些类型感染的新策略。