Differences In Inflammatory Response Induced By Two Representatives Of Clades Of The Pandemic St258 Klebsiella Pneumoniae Clonal Lineage Producing Kpc-Type Carbapenemases

ST258-K. pneumoniae (ST258-KP) strains, the most widespread multidrug-resistant hospital -acquired pathogens, belong to at least two clades differing in a 215 Kb genomic region that includes the cluster of capsule genes. To investigate the effects of the different capsular phenotype on host-pathogen interactions, we studied representatives of ST258-KP clades, KKBO-1 and KK207-1, for their ability to activate monocytes and myeloid dendritic cells from human immune competent hosts. The two ST258-KP strains strongly induced the production of inflammatory cytokines. Significant differences between the strains were found in their ability to induce the production of IL-1 beta: KK207-1/clade I was much less effective than KKBO-1/clade II in inducing IL-1 beta production by monocytes and dendritic cells. The activation of NLRP3 inflammasome pathway by live cells and/or purified capsular polysaccharides was studied in monocytes and dendritic cells. We found that glibenclamide, a NLRP3 inhibitor, inhibits more than 90% of the production of mature IL-1 beta induced by KKBO1 and KK207-1. KK207-1 was always less efficient compared to KKBO-1 in: a) inducing NLRP3 and pro-IL-1 beta gene and protein expression; b) in inducing caspase-1 activation and prod L113 cleavage. Capsular composition may play a role in the differential inflammatory response induced by the ST258-KP strains since capsular polysaccharides purified from bacterial cells affect NLRP3 and pro-IL-1 beta gene expression through p38MAPK-and NF-kappa B-mediated pathways. In each of these functions, capsular polysaccharides from KK207-1 were significantly less efficient compared to those purified from KKBO-1. On the whole, our data suggest that the change in capsular phenotype may help bacterial cells of Glade Ito partially escape innate immune recognition and IL-1 beta-mediated inflammation.