Hipervirülan Klebsiella pneumoniae'da peg-344'ün makrofajlarin otofaji yanitlarini baskilamadaki rolü

Hypervirulent Klebsiella pneumoniae (hvKp) poses a significant challenge due to its increased pathogenicity and increasing antibiotic resistance. Because of this reason it is important to understand the pathogenesis of the bacteria as well as the alternative therapies. In this study we aimed to address the role of the peg-344 gene of Klebsiella pneumoniae in autophagy and immune response suppression. Intracellular survival revealed that hvKp is significantly less internalized by macrophages than cKp (p=0.0001). hvKp showed 3-log higher intracellular CFU compared to cKp at 24H (p=0.0022) while causing lower cytotoxicity on macrophages. When autophagy is externally activated with Torin 1, the intracellular growth of hvKp still persists. Infection with hvKp significantly increases autophagy activation (Chloroquine, conversion of LC3-I to LC3-II). However, the persistent presence of p62 and low cytotoxicity suggest the bacterium blocks the fusion of phagosomes with lysosomes, enabling its survival within macrophages. ELISA experiments showed significantly lower TNF-α and IL-1β release against hvKp isolates was observed, showing that hvKp escapes macrophage immune responses. Deletion of peg-344 gene reversed the lower internalization and intracellular survival compared to peg-344 intact isolate. Peg-344 deletion also caused the loss of lower pro-inflammatory cytokine release and autophagy activation. All of these findings further support the idea that peg-344 may suppress macrophage autophagy responses. In conclusion, the study suggests that hypervirulent Klebsiella employs mechanisms to survive within macrophages, evade immune responses, and suppress autophagy. The peg-344 gene appears to play a significant role in these processes, contributing to both intracellular survival and immune/autophagy evasion.