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DiaComp Funded Abstracts

Program Application Abstract
The role of keratinocytes in MRSA infection during hyperglycemia
Patel, Shivani   (Columbia University in the City of New York)
Mentor: Parker, Dane (Columbia University)
Skin and soft tissue infections can have significantly different progressions and outcomes between non-diabetic and diabetic patients, particularly when caused by methicillin-resistant Staphylococcus aureus. In vivo experiments in streptozocin-treated mice showed both increased bacterial counts and larger areas of dermonecrosis compared to wild-type mice. Through our research, we hypothesized that hyperglycemia can cause dysfunction of keratinocytes leading to Staphylococcus aureus infection. Primary keratinocytes and immortalized human keratinocyte cell line (HaCaTs) were tested in vitro for their capacity to kill S.aureus intracellularly. This was tested by performing gentamicin protection assays on keratinocytes that had been cultured in the presence of euglycemic (6mM) and hyperglycemic (50mM) levels of glucose. Bacterial counts were also assessed in the supernatants. However, in primary keratinocytes nor HaCaTs no changes in killing were detected and no difference in bacterial uptake were noted. Rather in both live and heat-killed S. aureus infection, keratinocytes grown in a hyperglycemic environment produced decreased IL-1ß, a proinflammatory cytokine. We also observed keratinocytes grown in high glucose to possess decreased glycolytic function. Immortalized bone marrow-derived macrophages were also grown in vitro in euglycemic (5mM) and hyperglycemic (30mM) conditions. In high glucose conditions, a reduction of intracellular bacteria killing was observed, however, there was no difference in bacterial counts of the supernatants. Reactive oxygen species at basal levels were increased in hyperglycemic conditions and upon infection with S.aureus, those levels were exacerbated. Under condition of hyperglycemia both macrophages and keratinocytes are dysfunctional through different mechanisms.