title: Differences in Inflammatory Response Induced by Two Representatives of Clades of the Pandemic ST258 Klebsiella pneumoniae Clonal Lineage Producing KPC-Type Carbapenemases.
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.
authors.affiliation: Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Castronovo
authors.affiliation: Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy.
authors.forename: Ann Maria
authors.initials: AM
authors.lastname: Clemente
authors.affiliation: Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy.|Department of Medical Biotechnologies, University of Siena, Siena, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Antonelli
authors.affiliation: Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy.|Department of Medical Biotechnologies, University of Siena, Siena, Italy.
authors.forename: Marco Maria
authors.initials: MM
authors.lastname: D'Andrea
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Firenze, Firenze, Italy.
authors.forename: Michele
authors.initials: M
authors.lastname: Tanturli
authors.affiliation: Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy.
authors.forename: Eloisa
authors.initials: E
authors.lastname: Perissi
authors.affiliation: Department of Health Sciences, University of Firenze, Firenze, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Paccosi
authors.affiliation: Department of Health Sciences, University of Firenze, Firenze, Italy.
authors.forename: Astrid
authors.initials: A
authors.lastname: Parenti
authors.affiliation: Department of Experimental and Clinical Biomedical Sciences, University of Firenze, Firenze, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Cozzolino
authors.affiliation: Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy.|Department of Medical Biotechnologies, University of Siena, Siena, Italy.|Clinical Microbiology and Virology Unit, Careggi University Hospital, Firenze, Italy.|IRCCS Don Carlo Gnocchi Foundation, Firenze, Italy.
authors.forename: Gian Maria
authors.initials: GM
authors.lastname: Rossolini
authors.affiliation: Department of Experimental and Clinical Medicine, University of Firenze, Firenze, Italy.
authors.forename: Maria Gabriella
authors.identifier: http://orcid.org/0000-0003-4740-4646
authors.initials: MG
authors.lastname: Torcia
mesh_terms: D001426:Bacterial Proteins / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D004705:Endocytosis; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism; D053583:Interleukin-1beta / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000032:analysis; D007710:Klebsiella Infections / Q000201:enzymology / Q000276:immunology / Q000382:microbiology; D007711:Klebsiella pneumoniae / Q000201:enzymology* / Q000302:isolation & purification; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D016328:NF-kappa B / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000235:genetics / Q000378:metabolism; D011135:Polysaccharides, Bacterial / Q000302:isolation & purification / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis; D001618:beta-Lactamases / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D015850:Interleukin-6; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D011135:Polysaccharides, Bacterial; D014409:Tumor Necrosis Factor-alpha; D048051:p38 Mitogen-Activated Protein Kinases; D020170:Caspase 1; D001618:beta-Lactamases; C063912:carbapenemase