2. Academic Validation
  3. Inappropriate use of antibiotics exacerbates inflammation through OMV-induced pyroptosis in MDR Klebsiella pneumoniae infection

Inappropriate use of antibiotics exacerbates inflammation through OMV-induced pyroptosis in MDR Klebsiella pneumoniae infection

  • Cell Rep. 2021 Sep 21;36(12):109750. doi: 10.1016/j.celrep.2021.109750.
Chao Ye 1,  Weiran Li 1,  Ying Yang 2,  Qingwen Liu 2,  Sijing Li 3,  Peng Zheng 1,  Xiao Zheng 4,  Ye Zhang 1,  Jinrong He 2,  Yongjun Chen 1,  Liangqun Hua 4,  Zhongqian Yang 1,  Duo Li 1,  Zhaoling Ren 5,  Ying Yang 1,  Jialong Qi 1,  Weiwei Huang 6,  Yanbing Ma 7
Affiliations

Affiliations

  • 1 Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, Yunnan 650106, China.
  • 2 Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, Yunnan 650106, China; Laboratory of Molecular Immunology, Kunming Medical University, Kunming, Yunnan 650500, China.
  • 3 Jiangsu Center for the Collaboration and Innovation of Cancer Biotherapy, Cancer Institute, Xuzhou Medical University, Xuzhou, Jiangsu 221000, China.
  • 4 Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, Yunnan 650106, China; Yunnan University, Kunming, Yunnan 650504, China.
  • 5 Laboratory of Molecular Immunology, Kunming Medical University, Kunming, Yunnan 650500, China.
  • 6 Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, Yunnan 650106, China. Electronic address: [email protected].
  • 7 Laboratory of Molecular Immunology, Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, Yunnan 650106, China. Electronic address: [email protected].
PMID: 34551309 DOI: 10.1016/j.celrep.2021.109750
Abstract

The inappropriate use of Antibiotics is a severe public health problem worldwide, contributing to the emergence of multidrug-resistant (MDR) bacteria. To explore the possible impacts of the inappropriate use of Antibiotics on the immune system, we use Klebsiella pneumoniae (K. pneumoniae) Infection as an example and show that imipenem increases the mortality of mice infected by MDR K. pneumoniae. Further studies demonstrate that imipenem enhances the secretion of outer membrane vesicles (OMVs) with significantly elevated presentation of GroEL, which promotes the phagocytosis of OMVs by macrophages that depends on the interaction between GroEL and its receptor, lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). OMVs cause the Pyroptosis of macrophages and the release of proinflammatory cytokines, which contribute to exacerbated inflammatory responses. We propose that the inappropriate use of Antibiotics in the cases of Infection by MDR bacteria such as K. pneumoniae might cause damaging inflammatory responses, which underlines the pernicious effects of inappropriate use of Antibiotics.

Keywords

Klebsiella pneumoniae; OMV; antibiotics; carbapenem; inflammation; macrophage; outer membrane vesicle; pyroptosis.

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