Role of Staphylococcus aureus Formate Metabolism during Prosthetic Joint Infection

Biofilms are bacterial communities characterized by antibiotic tolerance. Staphylococcus aureus is a leading cause of biofilm infections on medical devices, including prosthetic joints, which represent a significant health care burden. The major leukocyte infiltrate associated with S. aureus prosthetic joint infection (PJI) is granulocytic myeloid-derived suppressor cells (G-MDSCs), which produce IL-10 to promote biofilm persistence by inhibiting monocyte and macrophage proinflammatory activity. To determine how S. aureus biofilm responds to G-MDSCs and macrophages, biofilms were cocultured with either leukocyte population followed by RNA sequencing. Several genes involved in fermentative pathways were significantly upregulated in S. aureus biofilm following G-MDSC coculture, including formate acetyltransferase (pflB), which catalyzes the conversion of pyruvate and coenzyme-A into formate and acetyl-CoA. A S. aureus pflB mutant (Delta pflB) did not exhibit growth defects in vitro. However, Delta pflB formed taller and more diffuse biofilm compared to the wild-type strain as revealed by confocal microscopy. In a mouse model of PJI, the bacterial burden was significantly reduced with Delta pflB during later stages of infection, which coincided with decreased G-MDSC influx and increased neutrophil recruitment, and Delta pflB was more susceptible to macrophage killing. Although formate was significantly reduced in the soft tissue surrounding the joint of Delta pflB-infected mice levels were increased in the femur, suggesting that host-derived formate may also influence bacterial survival. This was supported by the finding that a Delta pflB Delta fdh strain defective in formate production and catabolism displayed a similar phenotype to Delta pflB. These results revealed that S. aureus formate metabolism is important for promoting biofilm persistence.

Automated summary

Biofilms formed by Staphylococcus aureus on medical devices are a significant healthcare burden, and a type of white blood cell, G-MDSCs, promote biofilm persistence by inhibiting the activity of other immune cells. This study found that S. aureus promotes biofilm formation and survival through formate metabolism.