Determinants of Ocular Surface Biogeography

眼表生物地理学的决定因素

• 批准号: 10396467
• 负责人: Michael S Gilmore
• 金额: $ 41.23万
• 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 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10396467
• 关键词: Anatomy; Antibiotic Resistance; Automobile Driving; Biological Markers; Blindness; Botany; Caring; Chemicals; Communicable Diseases; Cornea; Data; Development; Epithelial; 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; 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.

眼睛的湿上皮表面在化学，免疫学上是在生态上独特的，并且 尽管从周围的Adnexa的角化表面上可以明显看出它。 这将对影响和感染这些不同位点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产生了深远的影响 金黄色葡萄球菌（MRSA）感染了湿与角质化的眼上皮组织。生物地理学的研究 长期以来一直在动物学和植物学中建立，但是仅由于基因组学给我们高分辨率 在各种解剖位点查看微生物之间的区别的能力，是否有可能研究 人类解剖学的生物地理学，包括眼睛和周围的组织，及其对感染性的影响 疾病。我们使用这种新的生物地理镜头来查看眼表面景观，并在初步数据中查看 首次表明，在所有解剖部位，多药抗眼感染的主要原因， MRSA专门感染了Adnexa的角质上皮表面与角化上皮的感染。 理解为什么一个MRSA谱系CC5/USA100的差距有一个危险的差距 角膜和结膜。由于眼表感染是全球视力丧失的主要原因，并且 CC5/USA100 MRSA代表了最高度抗生素的MRSA进化枝，迫切需要 了解MRSA生物地理学的驱动因素。实现我们的目标将确定确切的主机 在另一个MRSA谱系中选择另一个谱系的条件将确定宿主因素 为此选择做出贡献，并将确定将CC5菌株差异化的微生物因素 坚持在眼表面的湿上皮，作为感染的森林人。这一点的重要性 信息是，它将提供新的至关重要的见解，以使眼保健专业人员能够管理 通过发现生物标志物和钥匙眼，可以减少感染的可能性，以减少感染的可能性 表面防御。此外，它将确定病原MRSA谱系的关键特征，现在可以针对目标 在治疗上。填补这一关键知识差距将是使该领域向前迈进的重大进步 减轻重要的全球视力丧失原因。