Comparative genomics of the skin microbiome and associated isolates of patients undergoing mastectomy with immediate breast reconstruction

Mastectomy with immediate breast implant reconstruction (IBIR) is an increasingly common component of breast cancer treatment; however, these procedures carry a substantial risk of surgical site infections (SSIs) and noninfectious wound complications (NIWCs). We hypothesized that the local skin microbiota may contribute to the development of post-operative complications, in part by serving as a reservoir for pathobionts, such as Staphylococcus epidermidis and Cutibacterium acnes . We collected skin and intraoperative samples from 60 patients undergoing mastectomy with IBIR. To evaluate longitudinal shifts in community composition, we performed 16S rRNA gene sequencing of 151 breast and axilla skin swabs collected at pre- and post-operative time points. Using a comprehensive culture approach, we recovered diverse cultivable organisms and selected 232 S. epidermidis and 130 C. acne s isolates from skin swabs, implant swabs, and seroma fluid for whole-genome sequencing and comparative genomic analysis. We observed perturbations to community structure in the breast and axilla following mastectomy. These shifts were characterized by a significant and persistent depletion of Corynebacterium spp . , which did not resolve in patients who subsequently developed an SSI. We also uncovered outcome-specific genomic signatures in S. epidermidis isolates, which may offer mechanistic insight into the role of this species in SSI and NIWC development. Importantly, we also identified genomic signatures detectable prior to mastectomy and infection diagnosis that may offer clinical utility toward predicting post-operative complications. Together, these findings illustrate the importance of the skin microbiome in SSI and NIWC development following mastectomy with IBIR. IMPORTANCE An improved understanding of the relationship between surgical sites and adjacent resident skin microbiota can help identify which patients are at increased risk for developing surgical site infections and noninfectious wound complications. By characterizing bacterial communities before mastectomy with immediate breast reconstruction and during subsequent healing, we sought to evaluate how changes in community composition may contribute to the development of post-operative complications. We also performed in-depth genomic analyses of Staphylococcus epidermidis and Cutibacterium acnes isolates recovered from patients to identify genetic components that may determine whether an isolate protects or predisposes patients toward development of post-operative complications. Last, we identified genomic signatures detectable prior to surgery and infection diagnosis that are correlated with patient outcome, which may serve as informative biomarkers to inform patient care.