Supernatant of platelet-
Klebsiella pneumoniae
coculture induces apoptosis-like death in
Klebsiella pneumoniae
Authors: Wang Wenting , Chen Yaozhen , Chen Yutong , Liu Erxiong , Li Jing , An Ning , Xu Jinmei , Gu Shunli , Dang Xuan , Yi Jing , An Qunxing , Hu Xingbin , Yin Wen 
Published: January 2024

ABSTRACT

Multidrug-resistant
Klebsiella pneumoniae
strains, especially carbapenem-resistant
K. pneumoniae
, 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
K. pneumoniae
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-
K. pneumoniae
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
K. pneumoniae
and CRKP and detected turbidity changes in
K. pneumoniae
and CRKP cultures when grown with platelet-
K. pneumoniae
coculture supernatant added to the culture medium. We found that platelet-
K. pneumoniae
coculture supernatant significantly inhibited the growth of
K. pneumoniae
and CRKP
in vitro
. Furthermore, transfusion of platelet-
K. pneumoniae
coculture supernatant alleviated the symptoms of
K. pneumoniae
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
K. pneumoniae
following treatment with the supernatant. Our study demonstrates that the platelet-
K. pneumoniae
coculture supernatant can inhibit
K. pneumoniae
growth by inducing an apoptosis-like death, which is important for the antibacterial strategies development in the future.

IMPORTANCE

With 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.
K. pneumoniae
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-
K. pneumoniae
coculture supernatant can inhibit
K. pneumoniae
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.