TY - JOUR
T1 - Phagocytosis and Killing of Carbapenem-Resistant ST258 Klebsiella pneumoniae by Human Neutrophils
AU - Kobayashi, Scott D.
AU - Porter, Adeline R.
AU - Dorward, David W.
AU - Brinkworth, Amanda J.
AU - Chen, Liang
AU - Kreiswirth, Barry N.
AU - Deleo, Frank R.
N1 - Funding Information:
This work was supported by the National Institutes of Health (NIH; grant R01AI090155 to B. N. K.) and the Intramural Research Program, National Institute of Allergy and Infectious Diseases, NIH
Publisher Copyright:
© 2016 The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved.
PY - 2016/5/15
Y1 - 2016/5/15
N2 - 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 ST258 K. 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 ST258 K. pneumoniae.
AB - 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 ST258 K. 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 ST258 K. pneumoniae.
KW - Klebsiella pneumoniae
KW - Neutrophil
KW - Phagocytosis
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U2 - 10.1093/infdis/jiw001
DO - 10.1093/infdis/jiw001
M3 - Article
C2 - 26768252
AN - SCOPUS:84969921417
SN - 0022-1899
VL - 213
SP - 1615
EP - 1622
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 10
ER -