Klebsiella pneumoniae ST258 impairs intracellular elastase mobilization and persists within human neutrophils

Abstract

Klebsiella pneumoniae (Kp) strains of sequence type (ST) 258 producing K. pneumoniae-carbapenemase (KPC) are a major cause of hospital-associated outbreaks and the main contributors of carbapenemase spreading. Here, we deepen into the mechanisms behind the inhibition of neutrophil bactericidal functions mediated by a clinical isolate of Kp ST258 KPC, Kp from now on. We found that NETs formation induced by different stimuli (PMA, ionomycin, Staphylococcus aureus) was significantly reduced in the presence of Kp. We revealed that Kp affects actin polymerization which correlates with impaired mobilization of elastase from azurophilic granules to the nucleus and reduced elastase mobilization towards phagosomes that contain bacteria. In line with these results, Kp survived within neutrophils for 3 h post-challenge without compromising neutrophil viability. We also found that different Kp clinical isolates inhibited NETs formation and actin polymerization. These results describe a strategy of evasion used by Kp to subvert PMN-mediating both intra and extracellular mechanisms of killing, representing a clear advantage for the survival and spreading of this multidrug-resistant bacteria.