Supernatant of platelet- coculture induces apoptosis-like death in .

Multidrug-resistant strains, especially carbapenem-resistant , have become a rapidly emerging crisis worldwide, greatly limiting current therapeutic options and posing new challenges to infection management. Therefore, it is imperative to develop novel and effective biological agents for the treatment of multidrug-resistant infections. Platelets play an important role in the development of inflammation and immune responses. The main component responsible for platelet antibacterial activity lies in the supernatant stimulated by gram-positive bacteria. However, little research has been conducted on the interaction of gram-negative bacteria with platelets. Therefore, we aimed to explore the bacteriostatic effect of the supernatant derived from platelet- coculture and the mechanism underlying this effect to further assess the potential of platelet-bacterial coculture supernatant. We conducted this study on the gram-negative bacteria and CRKP and detected turbidity changes in and CRKP cultures when grown with platelet- coculture supernatant added to the culture medium. We found that platelet- coculture supernatant significantly inhibited the growth of and CRKP . Furthermore, transfusion of platelet- coculture supernatant alleviated the symptoms of and CRKP infection in a murine model. Additionally, we observed apoptosis-like changes, such as phosphatidylserine exposure, chromosome condensation, DNA fragmentation, and overproduction of reactive oxygen species in following treatment with the supernatant. Our study demonstrates that the platelet- coculture supernatant can inhibit growth by inducing an apoptosis-like death, which is important for the antibacterial strategies development in the future.IMPORTANCEWith the widespread use of antibiotics, bacterial resistance is increasing, and a variety of multi-drug resistant Gram-negative bacteria have emerged, which brings great challenges to the treatment of infections caused by Gram-negative bacteria. Therefore, finding new strategies to inhibit Gram-negative bacteria and even multi-drug- resistant Gram-negative bacteria is crucial for treating infections caused by Gram-negative bacteria, improving the abuse of antibiotics, and maintaining the balance between bacteria and antibiotics. is a common clinical pathogen, and drug-resistant CRKP is increasingly difficult to cure, which brings great clinical challenges. In this study, we found that the platelet- coculture supernatant can inhibit growth by inducing an apoptosis-like death. This finding has inspired the development of future antimicrobial strategies, which are expected to improve the clinical treatment of Gram-negative bacteria and control the development of multidrug-resistant strains.