Iron-Sulfur Cluster Repair Contributes to Yersinia pseudotuberculosis Survival within Deep Tissues.

To successfully colonize host tissues, bacteria must respond to and detoxify many different host-derived antimicrobial compounds, such as nitric oxide (NO). NO has direct antimicrobial activity through attack on iron-sulfur (Fe-S) cluster-containing proteins. NO detoxification plays an important role in promoting bacterial survival, but it remains unclear if repair of Fe-S clusters is also important for bacterial survival within host tissues. Here we show that the Fe-S cluster repair protein YtfE contributes to the survival of within the spleen following nitrosative stress. forms clustered centers of replicating bacteria within deep tissues, where peripheral bacteria express the NO-detoxifying gene expression also occurred specifically within peripheral cells at the edges of microcolonies. In the absence of , the area of microcolonies was significantly smaller than that of the wild type (WT), consistent with contributing to the survival of peripheral cells. The loss of did not alter the ability of cells to detoxify NO, which occurred within peripheral cells in both WT and Δ microcolonies. In the absence of NO-detoxifying activity by , NO diffused across Δ microcolonies, and there was a significant decrease in the area of microcolonies lacking , indicating that also contributes to bacterial survival in the absence of NO detoxification. These results indicate a role for Fe-S cluster repair in the survival of within the spleen and suggest that extracellular bacteria may rely on this pathway for survival within host tissues.