Determinants of Ocular Surface Biogeography

眼表生物地理学的决定因素

• 批准号: 10596574
• 负责人: Michael S Gilmore
• 金额: $ 42.5万
• 依托单位: MASSACHUSETTS EYE AND EAR INFIRMARY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10596574
• 关键词: Anatomy; Antibiotic Resistance; Automobile Driving; Biological Markers; Blindness; Botany; Caring; Chemicals; Communicable Diseases; Cornea; Data; Development; Epithelium; Eye; Eye Infections; Genomics; Human; Immunologics; In Vitro; Infection; Infectious Skin Diseases; Integration Host Factors; Intuition; Knowledge; Life; Microbe; Modeling; Molecular; Mucous Membrane; Multi-Drug Resistance; Mus; Pathogenicity; Positioning Attribute; Property; Research; Resolution; Site; Skin Tissue; Soft Tissue Infections; Surface; Time; Tissues; Zoology; antimicrobial; conjunctiva; empowerment; insight; keratinization; lens; methicillin resistant Staphylococcus aureus; microbial; ocular surface; residence; senescence; soft tissue; targeted treatment; transposon sequencing

The wet epithelial surface of the eye is chemically, immunologically and as a result, ecologically unique and profoundly different from the keratinized surfaces of the surrounding adnexa. Although it is intuitively obvious that this would have a substantial impact on the microbes that inhabit and infect these distinct sites on the ocular landscape, we show in preliminary data that this has profound consequences for the types of methicillin resistant S. aureus (MRSA) that infect wet versus keratinized ocular epithelial tissues. The study of biogeography has been long established in zoology and botany, however only since genomics has given us the high‐resolution power to view distinctions between microbes at various anatomical sites, has it been possible to study the biogeography of the human anatomy, including the eye and surrounding tissues – and its impact on infectious diseases. We used this new biogeographical lens to view the ocular surface landscape, and in preliminary data showed for the first time, that a leading cause of multidrug resistant ocular infections at all anatomical sites, MRSA, specializes in infecting the ocular wet epithelial surface versus the keratinized epithelium of the adnexa. There is a critical gap in understanding why one MRSA lineage, CC5/USA100, is better positioned to infect the cornea and conjunctiva. As ocular surface infections are leading causes of vision loss worldwide, and CC5/USA100 MRSA represent the most highly antibiotic resistant MRSA clade, there is an urgency to understanding the drivers of MRSA biogeography for the eye. Achieving our aims will identify the precise host conditions under which selection for one MRSA lineage over another occurs, will identify the host factors contributing to this selection, and will identify the microbial factors that differentially empower CC5 strains to persist on the wet epithelium of the ocular surface as a forerunner to infection. The importance of this information is that it will provide new and critical insights that will allow eye care professionals to manage the ocular surface in a way that will reduce the likelihood of infection, by discovering biomarkers and key ocular surface defenses. Further, it will identify critical features of pathogenic MRSA lineages that now can be targeted therapeutically. Filling this critical knowledge gap will be a major advance for driving the field forward to mitigate an important global cause of vision loss.

眼睛的湿润上皮表面在化学上、免疫学上以及因此在生态学上是独特的， 与周围附件的角质化表面有很大不同。虽然直觉上很明显 这将对栖息和感染眼部这些不同部位的微生物产生重大影响， 景观，我们在初步数据中表明，这对耐甲氧西林的类型有深远的影响， S.金黄色葡萄球菌（MRSA），其感染湿的与角化的眼上皮组织。历史学的研究 早在动物学和植物学中就已经建立，然而，只是因为基因组学给了我们高分辨率的 在不同的解剖部位观察微生物之间的区别，是否有可能研究 人体解剖学的血管造影，包括眼睛和周围组织-及其对感染的影响 疾病我们使用这种新的地理透镜来观察眼表景观，在初步数据中， 首次表明，在所有解剖部位， MRSA，专门感染眼部湿润上皮表面，而不是附件的角化上皮。 在理解为什么一个MRSA谱系CC 5/USA 100更好地感染 角膜和结膜由于眼表感染是全球视力丧失的主要原因， CC 5/USA 100 MRSA代表最高度抗生素耐药的MRSA分支，迫切需要 了解眼睛MRSA细菌谱的驱动因素。实现我们的目标将确定准确的主机 一种MRSA谱系相对于另一种的选择发生的条件，将识别宿主因素 有助于这种选择，并将确定微生物因素，差异授权CC 5菌株， 持续存在于眼表面的湿润上皮上，作为感染的先导。这一点的重要性 信息是，它将提供新的和关键的见解，将允许眼科护理专业人员管理 通过发现生物标志物和关键的眼表， 地面防御此外，它将确定致病性MRSA谱系的关键特征，现在可以针对 治疗上填补这一关键的知识空白将是推动该领域向前发展的一个重大进步， 减轻全球视力丧失的重要原因。