TheAccessory Gene Regulator (agr) Controls Staphylococcus Aureus Virulence In A Murine Intracranial Infection Model

Objective The purpose of this study is to construct the murine intracranial infectionmodel induced by S.aureus and investigate the role of agr system in this model.Methods S.aureus cells were injected with a micro-syringe into the mice frontal cortex toconstruct the animal model. The mice of control group were injected sterile saline instead ofS.aureus. After injection, the vital sign and survival rate of mice were observed to evaluate theinfection. The rectal temperature was monitored. At4hours and8hours after injection,hemogram was determined. Brain tissues were observed for pathology study at12hours.Histological examination was used to diagnose the pathological alterations of mouse tissues.The sensitivity of S.aureus to whole blood was evaluated by whole-blood killing assay.Results The mice in the model group demonstrated clinical signs of illness includinghunched posture, lethargy, spasm and finally dead. The earliest time point of death is12h.Compared with saline group, the48-hour mortality was significantly higher in model groupwhich were injected S.aureus8325-4. Meanwhile, neutrophil granulocyte infiltration in braintissue has been observed in model group. Although the number of white blood cells and therectal temperature of mice were not significantly altered in model group, the percentage ofneutrophil was significantly increased at the different time points after injection of S.aureus. In murine intracranial infection model, it was showed that the mortality caused by theaccessory gene regulator (agr) locus deficient strain was significant decreased compared withits parent strain. Moreover, we found that RNAIII, the effector of agr system, was essential forthe intracranial infection caused by S.aureus. In the further investigation, it was showed thatrestoration the expression of-toxin in agr deficient strain could partially recover themortality in the murine intracranial infection model.Conclusion Here, we have constructed the murine intracranial infection model inducedby S.aureus. Our data suggested that the agr system of S.aureus is an important virulencedeterminant in the induction and mortality of intracranial infection in mice.