The Pro-Inflammatory Effect of Staphylokinase Contributes to Community-Associated Staphylococcus Aureus Pneumonia

Abstract Pneumonia caused by community-associated Staphylococcus aureus (CA-SA) has high morbidity and mortality. Pathogens can express a variety of virulence factors to promote infection. The game between the host immune system and pathogens determines the degree of infection and tissue damage, but its mechanism has not been well explored. In this study, we found that staphylokinase (SAK) is highly expressed in CA-SA lineage ST398 and promotes lung infection in both wild-type and cathelicidins-related antimicrobial peptide CRAMP knockout (CRAMP−/−) mice. Furthermore, our results showed that SAK can activate the host's innate immune inflammatory response. Importantly, SAK can promote the activation of NLRP3 inflammasome by increasing the production of ROS. This may be one of the important mechanisms of SAK aggravating CA-SA pneumonia after excluding its function of promoting fibrinolysis and neutralizing CRAMP. Our results emphasize the importance of controlling inflammation in acute lung infections, and also provides new insights into the pathogenesis of highly virulent CA-SA.