BibTex format
@article{Wanford:2021:10.1016/S2666-5247(21)00195-6,
author = {Wanford, JJ and Hames, RG and Carreno, D and Jasiunaite, Z and Chung, WY and Arena, F and Di, Pilato V and Straatman, K and West, K and Farzand, R and Pizza, M and Martinez-Pomares, L and Andrew, PW and Moxon, ER and Dennison, AR and Rossolini, GM and Oggioni, MR},
doi = {10.1016/S2666-5247(21)00195-6},
journal = {Lancet Microbe},
pages = {e695--e703},
title = {Interaction of Klebsiella pneumoniae with tissue macrophages in a mouse infection model and ex-vivo pig organ perfusions: an exploratory investigation},
url = {http://dx.doi.org/10.1016/S2666-5247(21)00195-6},
volume = {2},
year = {2021}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Background: Hypervirulent Klebsiella pneumoniae (hvKp) strains of capsule type K1 and K2 cause invasive infections associated with hepatic abscesses, which can be difficult to treat and are frequently associated with relapsing infections. Other K pneumoniae strains (non-hvKp), including lineages that have acquired carbapenem resistance, do not manifest this pathology. In this work we aimed to test the hypothesis that within-macrophage replication is a key mechanism underpinning abscess formation in hvKp infections. Methods: In this exploratory investigation, to study the pathophysiology of abscess formation, mice were intravenously infected with 10<sup>6</sup> colony forming units (CFU) of either hvKp isolates (six strains) or non-hvKp isolates (seven strains). Intracellular bacterial replication and neutrophil influx in liver and spleen was quantified by fluorescence microscopy of sliced cryopreserved organs of mice collected 30 min, 6 h, and 24 h after infection with the aim to provide data of bacterial association to Kupffer cells in the liver and to the different tissue macrophages in the spleen. Microbiological and microscopy analysis of an ex-vivo model of pig liver and spleen infection were used to confirm within-macrophage replication. Pig organs were perfused with heparinised, autologous pig's blood and injected with 6·5 × 10<sup>7</sup> CFU of hvKp K2 sequence type 25 strain GMR151. Blood and tissue biopsies collected before infection and 30 min, 1 h, 2 h, 3 h, 4 h, and 5 h after infection were used to measure bacterial counts and to identify the subcellular localisation of bacteria by immunohistochemistry analysis. Findings: We show that hvKp resisted phagocyte-mediated clearance and replicated in mouse liver macrophages to form clusters 6 h after infection, with a mean of 7·0 bacteria per Kupffer cell (SD 6·2); however, non-hvKp were efficiently cleared (mean 1·5 bacteria per cell [SD 1·1])
AU - Wanford,JJ
AU - Hames,RG
AU - Carreno,D
AU - Jasiunaite,Z
AU - Chung,WY
AU - Arena,F
AU - Di,Pilato V
AU - Straatman,K
AU - West,K
AU - Farzand,R
AU - Pizza,M
AU - Martinez-Pomares,L
AU - Andrew,PW
AU - Moxon,ER
AU - Dennison,AR
AU - Rossolini,GM
AU - Oggioni,MR
DO - 10.1016/S2666-5247(21)00195-6
EP - 703
PY - 2021///
SP - 695
TI - Interaction of Klebsiella pneumoniae with tissue macrophages in a mouse infection model and ex-vivo pig organ perfusions: an exploratory investigation
T2 - Lancet Microbe
UR - http://dx.doi.org/10.1016/S2666-5247(21)00195-6
VL - 2
ER -