Antibiotic Tolerance and Therapeutic Failure in Diabetic Infections

An important health problem affecting veterans and Americans with type 2 diabetes is the high rate of diabetic foot infection (DFI) and is most often caused by the bacterium Staphylococcus aureus. For people with diabetes, these infections are harder to treat and often result in antibiotic therapeutic failure, which can lead to antibiotic resistance. We hypothesize that the metabolic state of the host can impact bacterial metabolism and contribute to altered antibiotic susceptibility in the microbiome and in diabetic foot infections (DFI). The goal of this project is to define the antibiotic response of the total microbiome in the gut as well as S. aureus in the hindfoot infection in hyperglycemic mice. Over the past year, we have made progress in writing up the results of Aim 2 of the proposal. This manuscript was submitted to Cell Reports, and we are in the process of conducting experiments and revisions requested by the reviewers and editor. This work outlines our data on the impact of hyperglycemia on the murine microbiome with and without antibiotic exposure. Our new data indicate that hyperglycemia predisposes the microbiome to antibiotic-induced perturbation as well as post-antibiotic colonization with enteric pathogens. During the remaining time of the NCE we aim to finalize revisions to the Cell Reports manuscript and resubmit. During the past year, we have also published a related article in MSystems.