Hypermucoviscous Klebsiella pneumoniae infections induce platelet aggregation and apoptosis and inhibit maturation of megakaryocytes

Abstract

Introduction: Different Klebsiella pneumoniae strains carry different virulence factors and antibiotic resistance and may cause thrombocytopenia. This study aimed to investigate the effects of different infections caused by K. pneumoniae on platelets.

Methods: Two hypermucoviscous K. pneumoniae strains and two classic strains were collected from clinical blood culture, and in both groups, there was a carbapenem-resistant strain and a carbapenem-sensitive strain. Mouse infection models were constructed by intraperitoneally injecting different strains, and mice injected with phosphate-buffered saline served as a control. Count, aggregation rate and apoptosis proportion of platelets within 12 h were examined. CD41 expression was measured in bone marrow cells to determine the maturation of megakaryocytes. The concentrations of lipopolysaccharides and related signaling molecules were also measured.

Results: The platelet aggregation rate was much significantly higher in the two hypermucoviscous groups, while it showed no difference in the classic groups compared to the control group. All infections induced apoptosis of platelets, among which the highest apoptosis proportions were observed in infections caused by the hypermucoviscous carbapenem-sensitive strain. In both hypermucoviscous groups the CD41 mean fluorescence intensity was much lower than that in the control group, indicating that the maturation of megakaryocytes in the hypermucoviscous groups was significantly inhibited. Lipopolysaccharides were significantly higher and TLR4/Myd88 and JNK/MAPK pathways were strongly activated in hypermucoviscous groups.

Conclusions: The results indicate that hypermucoviscous K. pneumoniae can reduce platelet count by several pathways. Although antibiotic resistance is rapidly emerging worldwide, it has little influence on the decrease in platelets.

Keywords: Aggregation; Apoptosis; Carbapenem resistance; Hypermucoviscous; Klebsiella pneumoniae; Megakaryocytopoiesis; Platelets; Thrombocytopenia.