Articular Microbiome for Prediction and Potential Therapy of Periprosthetic Joint Infections

Project Summary Abstract The objective of the proposed research is to better understand how the native joint microbiome/phageome may contribute to the risk of subsequent periprosthetic joint infection (PJI) following joint replacement for primary knee osteoarthritis (OA). Our laboratory has previously examined the microbial DNA content of human and mouse cartilage and found that microbial DNA is present in normal and diseased cartilage. Furthermore, microbial species from which the DNA arose are altered during progression from healthy cartilage to intact sections of OA joints to eroded sections of OA joints. Our first (K99) Aim will generate a broad atlas of (bacterial) microbial DNA patterns within joint tissues and systemic microbiome samples among OA patients who subsequently developed PJI following joint replacement compared to those who did not. Our second (K99) Aim will perform a similar analysis of the virome with particular focus on bacteriophages. Our third (R00) Aim will leverage data generated in Aims 1 and 2 to identify phages and phage targets that may be useful for future, highly directed phage therapy to treat PJI. The proposed work is important, as we do not have a full understanding of how various microbiome niches influence the risk for PJI, which is a burdensome, disabling, and common complication of OA joint replacement. Our study uses innovative high-throughput sequencing in both low and high-biomass microbiome samples, building upon our previous custom protocols, and implements new and novel statistical analysis methods to identify viral and bacteriophage sequences within microbiome shotgun sequencing. Success in our proposal may open a new avenue for PJI prediction and potential phage- based PJI therapy.