Antimicrobial resistance is an expanding public health concern, with methicillin-resistant S. aureus (MRSA) as a prominent example. Increasing evidence is pointing to domestic animals, including those of agricultural importance, as reservoirs and shedders of MRSA, and animal-human interspecies transmission has been reported worldwide. Consequently, there is a need for additional approaches to control MRSA. Our long-term goal is to evaluate the efficacy of non-antibiotic biotherapeutics to control antibiotic-resistant bacteria.

Our team recently published on the ability of the mesenchymal stromal cell (MSC) secretome, consisting of various secreted biomolecules, to effectively control the growth of bacteria, including MRSA. Specifically, our findings were made with equine MSCs in the context of cutaneous MRSA infection. Our specific hypothesis is that the equine MSC secretome is an effective novel biotherapeutic to control MRSA. To test this, we will define the macromolecular nature of the MSC secretome that exhibits the anti-MRSA activity in vitro (Aim 1), analyze MSC secretome delivery systems using a 3D skin MRSA explant model ex vivo (Aim 2), and determine the efficacy of the MSC secretome to control MRSA in vivo (Aim 3).

The proposed work is innovative, because this is the first study to focus on the anti-MRSA activities of the MSC secretome. With respect to potential impact and expected outcomes, the results from this study will allow for the optimization of novel, evidence-based treatments that can be used as non-antibiotic biotherapeutics to control antibiotic-resistant bacteria in veterinary practice, including equines but other veterinary species as well.