title: Phagocytosis and Killing of Carbapenem-Resistant ST258 Klebsiella pneumoniae by Human Neutrophils.
abstract: Carbapenem-resistant Klebsiella pneumoniae strains classified as multilocus sequence type 258 (ST258) are among the most widespread multidrug-resistant hospital-acquired pathogens. Treatment of infections caused by these organisms is difficult, and mortality is high. The basis for the success of ST258, outside of antibiotic resistance, remains incompletely determined. Here we tested the hypothesis that ST258K. pneumoniae has enhanced capacity to circumvent killing by human neutrophils, the primary cellular defense against bacterial infections. There was limited binding and uptake of ST258 by human neutrophils, and correspondingly, there was limited killing of bacteria. On the other hand, transmission electron microscopy revealed that any ingested organisms were degraded readily within neutrophil phagosomes, thus indicating that survival in the neutrophil assays is due to limited phagocytosis, rather than to microbicide resistance after uptake. Our findings suggest that enhancing neutrophil phagocytosis is a potential therapeutic approach for treatment of infection caused by carbapenem-resistant ST258K. pneumoniae.
authors.affiliation: Laboratory of Bacteriology.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Kobayashi
authors.affiliation: Laboratory of Bacteriology.
authors.forename: Adeline R
authors.initials: AR
authors.lastname: Porter
authors.affiliation: Research Technologies Branch, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana.
authors.forename: David W
authors.initials: DW
authors.lastname: Dorward
authors.affiliation: Laboratory of Bacteriology.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Brinkworth
authors.affiliation: Public Health Research Institute Tuberculosis Center, New Jersey Medical School-Rutgers University, Newark.
authors.forename: Liang
authors.initials: L
authors.lastname: Chen
authors.affiliation: Public Health Research Institute Tuberculosis Center, New Jersey Medical School-Rutgers University, Newark.
authors.forename: Barry N
authors.initials: BN
authors.lastname: Kreiswirth
authors.affiliation: Laboratory of Bacteriology.
authors.forename: Frank R
authors.initials: FR
authors.lastname: DeLeo
mesh_terms: D000818:Animals; D015373:Bacterial Typing Techniques; D015780:Carbapenems / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D005260:Female; D006801:Humans; D007710:Klebsiella Infections / Q000382:microbiology / Q000628:therapy*; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000235:genetics / Q000276:immunology*; D058885:Multilocus Sequence Typing; D009504:Neutrophils / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D010587:Phagocytosis; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D015780:Carbapenems; D017382:Reactive Oxygen Species
keywords: Klebsiella pneumoniae; neutrophil; phagocytosis