Two ST11 Klebsiella pneumoniae strains exacerbate colorectal tumorigenesis in a colitis-associated mouse model

doi:10.1080/19490976.2021.1980348

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/23343

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/23343

Title:	Two ST11 Klebsiella pneumoniae strains exacerbate colorectal tumorigenesis in a colitis-associated mouse model
Authors:	Chiang, MK;Hsiao, PY;Liu, YY;Tang, HL;Chiou, CS;Lu, MC;Lai, YC
Keywords:	Klebsiella pneumoniae;ST11;colorectal tumorigenesis;IL-10;M2 macrophages
Date:	2021
Issue Date:	2022-08-05T09:35:44Z (UTC)
Publisher:	TAYLOR & FRANCIS INC
ISSN:	1949-0976
Abstract:	Sequence type (ST) 11 is one of the major lineages of carbapenem-resistant Klebsiella pneumoniae (CRKP). Although the gastrointestinal (GI) carriage of CRKP predisposes individuals to subsequent infections, little is known for its impact on gut homeostasis. In this study, we investigated the association between ST11 CRKP colonization and colorectal cancer (CRC). Two ST11 CRKP, KPC160111 (KL47) and KPC160132 (KL64), were selected as the representative strains. We used azoxymethane (AOM) and dextran sodium sulfate (DSS) to initiate a colitis-associated CRC model. Both strains established prolonged colonization in the GI tract of the AOM-DSS-treated BALB/c mice and aggravated gut dysbiosis. Under this AOM-DSS-induced setting, ST11 K. pneumoniae colonization significantly promoted the growth and progression of colorectal adenomas to high-grade dysplasia. Numerous crypts were formed inside the enlarged adenomas, in which CD163(+) tumor-associated macrophages accumulated. Similarly, ST11 K. pneumoniae also increased the population size of the CD163(+) macrophages with the M2 phenotype in the peritoneal cavity of LPS-primed BALB/c mice. When applied to RAW264.7 cells, ST11 K. pneumoniae polarized the macrophages toward an M2 phenotype through the inhibition of IKK-NF kappa B and the activation of STAT6-KLF4-IL-10. Through the M2-skewing ability, ST11 K. pneumoniae promoted the accumulation of CD163(+) macrophages in the adenomatous crypts to create an immunosuppressive niche, which not only accommodated the extended stay for its own sake but also deteriorated colorectal tumorigenesis.
URI:	http://dx.doi.org/10.1080/19490976.2021.1980348 https://www.webofscience.com/wos/woscc/full-record/WOS:000703337200001 https://ir.csmu.edu.tw:8080/handle/310902500/23343
Relation:	GUT MICROBES ,2021,v13,issue 1
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

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