Patients with type II diabetes (T2D) are vulnerable to many medical complications including periodontal disease (PD) and diabetic foot ulcers (DFUs), the latter of which frequently become infected with staphylococci. Diabetic foot ulcer infections (DFUIs) lead to substantial healthcare costs and significantly increase the risk of lower limb amputations which are lifechanging. We previously showed that periodontal pockets (formed as PD progresses) are a microbial reservoir of Staphylococcus epidermidis and can act as a gateway to the bloodstream, potentially leading to metastatic infections in immunocompromised individuals like those with diabetes. The hypothesis for the proposed research is that the oro-nasal cavity is a reservoir for DFUI via periodontal pockets and the bloodstream and/or by direct skin contact. This study utilises DNA microarray profiling and whole genome sequencing to comprehensively compare the genomes and molecular characteristics of staphylococci from multiple anatomical sites in patients with T2D to determine if oronasal and DFU-recovered staphylococci are genetically identical. A pilot investigation has revealed identical oro-nasal and DFU-recovered Staphylococcus aureus strains in multiple patients by WGS, providing very convincing evidence for a transmission pathway between these distinct sites. If so, DFUIs could be prevented using oronasal intervention and decolonisation measures. These treatments would also improve the periodontal and systemic health of patients with T2D. Electrochemically activated anolyte will be assessed as a topical alternative to antibiotic therapy for DFUI treatment, against the background of the current global antimicrobial resistance crisis. Anolyte (generated from brine), is environmentally friendly, inexpensive, non-toxic and highly microbiocidal. It has been shown to reduce bacterial load in wounds and promote tissue healing. The study outcomes will positively direct approaches towards DFUI prevention and develop a successful method of DFUI treatment if required. Improved patient outcomes will be benchmarked as a reduction of DFUI incidences and lower limb amputations.