STUDIES OF RESISTANCE TO 600 DA BPEI AND DRUG DELIVERY STRATEGIES FOR SKIN AND SOFT TISSUE INFECTIONS

Abstract

AbstractSkin and soft tissue infections (SSTIs) are a global health threat that affects almost 15 million patients annually. 1 These infections are most often caused by Methicillin-resistant Staphylococcus aureus (MRSA). Staphylococcus aureus is dangerous due to the virulence factors it secretes and its ability to remain in a quiescent biofilm state, MRSA is especailly dangerous because it has multidrug resistance, on top of the typical Stapylococcus aureus characteristic. Novel drugs are elusive due to the propensity of MRSA to develop resistance against new compounds. Therefore, there is a need for compounds that either A) bacteria cannot develop resistance to or B) can more effectively help the host clear resistant infections. In this regard, we envision our compound of interest (COI), 600 Da BPEI. BPEI has been shown to turn off pathogen resistance factors, disrupt biofilms, and modulate the host immune system in vitro. In this study, we showed that MRSA could develop resistance to BPEI, but when this resistance occurred, the MRSA appeared to be more susceptible to clearance by the host and had a decrease in virulence factors. Consistent with the phenotypical observations, WGS evealed data in genes related to virulence. Interestingly, the BPEI-resistant MRSA was susceptible to the model β- Lactam antibiotic oxacillin. These data, taken together, suggest that BPEI resistance may not appear in a clinical context as the host could potentially clear any resistant populations. Additionally, we have developed a biocompatible drug delivery system to release our COI in a designated area. This drug delivery system allows for the controlled delivery of our COI versus other methods that rely on specialized bandages. Our drug delivery system is composed of a non- immunogenic biologic with wound-healing characteristics. Lastly, we have developed a simple in vitro biofilm model that allows for the concomitant culturing of MRSA and Pseudomonas xvi aeruginosa, allowing for upstream drug discovery of potential treatments for polymicrobial infections. Keywords: SSTIs, BPEI, MRSA, Pseudomonas aeruginosa, Co-culture, polymicrobial, PEG- BPEI.