MODULATION OF NEUTROPHIL EXTRACELLULAR TRAPS RELEASE BY KLEBSIELLA PNEUMONIAE

FEDERICO BIRNBERG WEISS; ; CASTILLO, LUIS ALEJANDRO; PITTALUGA,JOSÉ R; DAIANA MARTIRE-GRECO; SONIA A. GÓMEZ;; LANDONI, VERÓNICA INÉS; FERNÁNDEZ, GABRIELA CRISTINA;

JOURNAL OF LEUKOCYTE BIOLOGY

FEDERATION AMER SOC EXP BIOL

Lugar: Bethesda; Año: 2021

0741-5400

One of the main bactericidal mechanisms of polymorphonuclear neutrophils(PMN) is the release of neutrophil extracellular traps (NETs), which capture anddestroy pathogens. Klebsiella pneumoniae (Kpn) producer of carbapenemase(KPC) and belonging to the sequence type 258 (ST258), is a hyper epidemic clonethat causes a large number of infections worldwide associated with highpersistence and mortality. It is necessary to investigate the interaction of Kpn KPCwith the immune system to improve prevention and treatment of infectionsmediated by this bacterium. Based on the hypothesis that Kpn is able to subvertPMN-mediated death, our aim was to assess whether Kpn KPC ST258 couldmodulate the bactericidal response of PMN, focusing on NETs formation,compared to another opportunistic pathogen, as Escherichia coli (Eco). Our resultsshowed that the release of NETs was absent when PMN were challenged with KpnKPC, while Eco was a strong inducer of NETosis. Moreover, Kpn KPC was able toinhibit NETosis induced by Eco. The inhibition of Kpn KPC-mediated NETsformation occurred by a reactive oxygen species (ROS) generation independentpathway, did not involve bacterial-released soluble factors or cell wall components,and was dependent on bacterial viability. Moreover, when degranulation wasinvestigated, we found that Kpn KPC affected only the mobilization of primarygranules, which harbor the proteins with more potent bactericidal properties andthose related to NETosis. In conclusion, Kpn KPC ST258 effectively managed toevade the PMN response by inhibiting the release of NETs, and primary granulemobilization