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.