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.

眼睛湿润的上皮表面具有化学、免疫学特征，因此具有独特的生态学特征。 尽管直观上很明显，但与周围附件的角化表面有很大不同。 这将对居住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，这对甲氧西林耐药性类型具有深远的影响 生物地理学研究表明，金黄色葡萄球菌（MRSA）感染湿眼上皮组织和角化眼上皮组织。 动物学和植物学早已建立，但直到基因组学为我们提供了高分辨率 能够观察不同解剖部位微生物之间的差异，是否有可能研究 人体解剖学的生物地理学，包括眼睛和周围组织 - 及其对传染性的影响 我们使用这种新的生物地理透镜来观察眼表景观并获得初步数据。 首次表明，这是所有解剖部位多重耐药性眼部感染的主要原因， MRSA 专门感染眼湿上皮表面和附件角化上皮。 在理解为何 MRSA 谱系 CC5/USA100 更适合感染 角膜和结膜感染是全世界视力丧失的主要原因，并且 CC5/USA100 MRSA 代表了抗生素耐药性最高的 MRSA 分支，迫切需要 了解 MRSA 眼睛生物地理学的驱动因素将确定精确的宿主。 一种 MRSA 谱系相对于另一种谱系的选择发生的条件，将确定宿主因素 有助于这种选择，并将确定使 CC5 菌株差异化的微生物因素 持续存在于眼表的湿润上皮上，是感染的先兆。 信息是，它将提供新的、重要的见解，使眼保健专业人员能够管理 通过发现生物标志物和关键的眼部疾病，以降低感染可能性的方式对眼表进行检测 此外，它将识别现在可以针对的致病性 MRSA 谱系的关键特征。 填补这一关键的知识空白将是推动该领域向前发展的重大进步。 减轻视力丧失的一个重要全球原因。