Carbohydrate Metabolism Affects Macrophage-Mediated Killing of Enterococcus faecalis

Enterococcus faecalis, an opportunistic pathogen that causes severe community-acquired and nosocomial infections, has been reported to resist phagocyte-mediated killing, which enables its long-term survival in the host. Metabolism, especially carbohydrate metabolism, plays a key role in the battle between pathogens and hosts. However, the function of carbohydrate metabolism in the long-term survival of E. faecalis in phagocytes has rarely been reported. In this study, we utilized transposon insertion sequencing (TIS) to investigate the function of carbohydrate metabolism during the survival of E. faecalis in RAW264.7 cells. The TIS results showed that the fitness of carbohydrate metabolism-related mutants, especially those associated with fructose and mannose metabolism, were significantly enhanced, suggesting that the attenuation of carbohydrate metabolism promotes the survival of E. faecalis in macrophages. The results of our investigation indicated that macrophages responded to carbohydrate metabolism of E. faecalis and polarized to M1 macrophages to increase nitric oxide (NO) production, leading to the enhancement of macrophage-mediated killing to E. faecalis. Meanwhile, E. faecalis automatically decreased carbohydrate metabolism to escape from the immune clearance of macrophages during intracellular survival. The shift of primary carbon resources for macrophages affected the ability to clear intracellular E. faecalis. In summary, the results of the present study demonstrated that carbohydrate metabolism affects the macrophage-mediated killing of E. faecalis. IMPORTANCE E. faecalis has become a major pathogen leading to a variety of infections around the world. The metabolic interaction between E. faecalis and its host is important during infection but is rarely investigated. We used transposon insertion sequencing coupled with transcriptome sequencing to explore the metabolic interaction between E. faecalis and macrophages and uncovered that the shift of carbohydrate metabolism dramatically affected the inflammatory response of macrophages. In addition, E. faecalis attenuated carbohydrate metabolism to avoid the activation of the immune response of macrophages. This study provides new insights for the reason why E. faecalis is capable of long-term survival in macrophages and may facilitate the development of novel strategies to treat infectious diseases.