Research Article: Differences in Inflammatory Response Induced by Two Representatives of Clades of the Pandemic ST258 Klebsiella pneumoniae Clonal Lineage Producing KPC-Type Carbapenemases

Date Published: January 12, 2017

Publisher: Public Library of Science

Author(s): Giuseppe Castronovo, Ann Maria Clemente, Alberto Antonelli, Marco Maria D’Andrea, Michele Tanturli, Eloisa Perissi, Sara Paccosi, Astrid Parenti, Federico Cozzolino, Gian Maria Rossolini, Maria Gabriella Torcia, Samithamby Jeyaseelan.

http://doi.org/10.1371/journal.pone.0170125

Abstract

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-1β: KK207-1/clade I was much less effective than KKBO-1/clade II in inducing IL-1β 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-1β induced by KKBO1 and KK207-1. KK207-1 was always less efficient compared to KKBO-1 in: a) inducing NLRP3 and pro-IL-1β gene and protein expression; b) in inducing caspase-1 activation and pro-IL-1β 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-1β gene expression through p38MAPK- and NF-κB-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 clade I to partially escape innate immune recognition and IL-1β-mediated inflammation.

Partial Text

Carbapenem-resistant Enterobacteriaceae, and especially Klebsiella pneumoniae (KP) producing the KPC-type carbapenemases (KPC-KP), have emerged as an important cause of healthcare-associated infections correlated with high morbidity and mortality [1–3]. The pandemic diffusion of KPC-KP has largely been contributed by the clonal expansion of strains belonging to sequence type (ST) 258 (ST258) producing either the KPC-2 or the KPC-3 carbapenemases [4–10].

Strains of ST258-KP can be segregated into two ST258 clades [4,11–14]. The major genetic divergence between these two clades is constituted by a 215-kb genomic region that includes the genes of the cps cluster. ST258-KP strains were shown to circumvent killing by human neutrophils [15,37] but no differences between strains with cpsBO-4 (clade 2) or cps207-2 (clade 1) were revealed [11] suggesting that capsule switch does not confer to strains of the ST258-KP clades an additional benefit in terms of resistance to neutrophil phagocytosis. Although neutrophil phagocytosis is important in host defense against K. pneumoniae infection, different cells of innate and/or adaptive immunity also play relevant roles in infection clearance. MDC first sense bacterial cells once they penetrate mucosal barriers and, following interaction with bacterial ligands, they produce large quantities of inflammatory mediators involved in the recruitment of neutrophils, as well as in T-cell activation and differentiation [38,39]. Inflammatory monocytes, involved in the clearance of ST258-KP infection in mice, [40,41] also may produce high amounts of inflammatory (TNFα, IL-1β) or anti-inflammatory cytokines [42,43].

 

Source:

http://doi.org/10.1371/journal.pone.0170125

 

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