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.

眼睛湿润的上皮表面在化学上、免疫学上是独特的，因此，在生态上是独特的 与周围附件的角质化表面有很大的不同。尽管直觉上很明显 这将对栖息并感染眼睛上这些不同部位的微生物产生重大影响 我们在初步数据中表明，这对甲氧西林耐药类型有深远的影响 感染湿性和角化性眼上皮组织的金黄色葡萄球菌(MRSA)。生物地理学的研究有 在动物学和植物学中已经建立了很长时间，然而直到基因组学给了我们高分辨率 观察不同解剖部位微生物之间的差异的能力，是否有可能研究 人体解剖的生物地理学，包括眼睛和周围组织-及其对传染性疾病的影响 疾病。我们使用这种新的生物地理透镜来观察眼表景观，并在初步数据中 首次表明，在所有解剖部位，耐多药眼部感染的主要原因之一， MRSA，专门感染眼部潮湿的上皮表面，而不是附件的角化上皮。 在理解为什么一种MRSA谱系CC5/USA100更适合感染 角膜和结膜。由于眼表感染是全球视力丧失的主要原因， CC5/USA100 MRSA代表了对抗生素耐药性最高的MRSA分支，迫切需要 了解眼部耐甲氧西林金黄色葡萄球菌生物地理的驱动因素。实现我们的目标将确定准确的东道主 选择一种MRSA谱系而不是另一种谱系的条件，将确定宿主因素 有助于这次选择，并将确定使CC5菌株具有不同能力的微生物因素 持续停留在湿润的眼表上皮细胞，作为感染的先兆。这件事的重要性 信息是，它将提供新的和关键的见解，使眼睛护理专业人员能够管理 通过发现生物标志物和关键眼部，减少感染的可能性 地面防御系统。此外，它将确定致病MRSA谱系的关键特征，现在可以作为靶点 从治疗上讲。填补这一关键的知识缺口将是推动该领域向前发展的重大进步 减轻全球视力丧失的一个重要原因。