Vissagan Gopalakrishnan1, Moses Kim2, Gary An2. 1. Department of Biology, Johns Hopkins University , Baltimore, Maryland. 2. Department of Surgery, University of Chicago , Chicago, Illinois.
Abstract
OBJECTIVE: Despite clinical advances, surgical site infections (SSIs) remain a problem. The development of SSIs involves a complex interplay between the cellular and molecular mechanisms of wound healing and contaminating bacteria, and here, we utilize an agent-based model (ABM) to investigate the role of bacterial virulence potential in the pathogenesis of SSI. APPROACH: The Muscle Wound ABM (MWABM) incorporates muscle cells, neutrophils, macrophages, myoblasts, abstracted blood vessels, and avirulent/virulent bacteria to simulate the pathogenesis of SSIs. Simulated bacteria with virulence potential can mutate to possess resistance to reactive oxygen species and increased invasiveness. Simulated experiments (t=7 days) involved parameter sweeps of initial wound size to identify transition zones between healed and nonhealed wounds/SSIs, and to evaluate the effect of avirulent/virulent bacteria. RESULTS: The MWABM reproduced the dynamics of normal successful healing, including a transition zone in initial wound size beyond which healing was significantly impaired. Parameter sweeps with avirulent bacteria demonstrated that smaller wound sizes were associated with healing failure. This effect was even more pronounced with the addition of virulence potential to the contaminating bacteria. INNOVATION: The MWABM integrates the myriad factors involved in the healing of a normal wound and the pathogenesis of SSIs. This type of model can serve as a useful framework into which more detailed mechanistic knowledge can be embedded. CONCLUSION: Future work will involve more comprehensive representation of host factors, and especially the ability of those host factors to activate virulence potential in the microbes involved.
OBJECTIVE: Despite clinical advances, surgical site infections (SSIs) remain a problem. The development of SSIs involves a complex interplay between the cellular and molecular mechanisms of wound healing and contaminating bacteria, and here, we utilize an agent-based model (ABM) to investigate the role of bacterial virulence potential in the pathogenesis of SSI. APPROACH: The Muscle Wound ABM (MWABM) incorporates muscle cells, neutrophils, macrophages, myoblasts, abstracted blood vessels, and avirulent/virulent bacteria to simulate the pathogenesis of SSIs. Simulated bacteria with virulence potential can mutate to possess resistance to reactive oxygen species and increased invasiveness. Simulated experiments (t=7 days) involved parameter sweeps of initial wound size to identify transition zones between healed and nonhealed wounds/SSIs, and to evaluate the effect of avirulent/virulent bacteria. RESULTS: The MWABM reproduced the dynamics of normal successful healing, including a transition zone in initial wound size beyond which healing was significantly impaired. Parameter sweeps with avirulent bacteria demonstrated that smaller wound sizes were associated with healing failure. This effect was even more pronounced with the addition of virulence potential to the contaminating bacteria. INNOVATION: The MWABM integrates the myriad factors involved in the healing of a normal wound and the pathogenesis of SSIs. This type of model can serve as a useful framework into which more detailed mechanistic knowledge can be embedded. CONCLUSION: Future work will involve more comprehensive representation of host factors, and especially the ability of those host factors to activate virulence potential in the microbes involved.
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