2. Academic Validation
  3. Outer membrane protein A inhibits the degradation of caspase-1 to regulate NLRP3 inflammasome activation and exacerbate the Acinetobacter baumannii pulmonary inflammation

Outer membrane protein A inhibits the degradation of caspase-1 to regulate NLRP3 inflammasome activation and exacerbate the Acinetobacter baumannii pulmonary inflammation

  • Microb Pathog. 2021 Apr;153:104788. doi: 10.1016/j.micpath.2021.104788.
Yumei Li 1,  Chunhong Peng 1,  Dan Zhao 1,  Laibing Liu 2,  Bing Guo 3,  Mingjun Shi 3,  Ying Xiao 3,  Zijiang Yu 1,  Yan Yu 1,  Baofei Sun 4,  Wenjuan Wang 5,  Jieru Lin 1,  Xiaoyan Yang 6,  Songjun Shao 1,  Xiangyan Zhang 7
Affiliations

Affiliations

  • 1 Department of Anatomy, School of Basic Medical Sciences, Guizhou Medical University/ Department of Respiratory and Critical Medicine, Guizhou Provincial People's Hospital, Guiyang, Guizhou, 550025, China.
  • 2 Department of Neurosurgery, Affiliated Baiyun Hospital, Guizhou Medical University, Guiyang, Guizhou, 550004, China.
  • 3 Guizhou Provincial Key Laboratory of Pathogenesis and Drug Research on Common Chronic Diseases, Guizhou Medical University, Guiyang, Guizhou, 550025, China.
  • 4 Department of Anatomy, School of Basic Medical Sciences, Guizhou Medical University/ Department of Respiratory and Critical Medicine, Guizhou Provincial People's Hospital, Guiyang, Guizhou, 550025, China; Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, Guizhou, 550025, China.
  • 5 Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, Guizhou, 550025, China.
  • 6 Department of Pediatrics, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550004, China.
  • 7 Department of Anatomy, School of Basic Medical Sciences, Guizhou Medical University/ Department of Respiratory and Critical Medicine, Guizhou Provincial People's Hospital, Guiyang, Guizhou, 550025, China. Electronic address: 136721361@qq.com.
PMID: 33571624 DOI: 10.1016/j.micpath.2021.104788
Abstract

Acinetobacter baumannii (A. baumannii), one of the major pathogens that causes severe nosocomial infections, is characterised by a high prevalence of drug resistance. It has been reported that A. baumannii triggers the NOD-like receptor 3 (NLRP3) inflammasome, but the role of its virulence-related outer membrane protein A (ompA) remains unclear. Therefore, this study aimed to explore the effects of ompA on the NLRP3 inflammasome and its underlying molecular mechanisms. Results showed that ompA enhanced inflammatory damage, which was reduced as a result of knockout of the ompA gene. Additionally, ompA-stimulated expression of NLRP3 inflammasome was significantly blocked by silencing Caspase-1, but activation of NLRP3 inflammasome was not altered after silencing ASC; this indicated that ompA was dependent on the Caspase-1 pathway to activate the inflammatory response. Simultaneously, the wild-type (WT) strains triggered NLRP3 inflammasome after inhibition of Caspase-1 degradation by Proteasome Inhibitor MG-132, aggravating tissue damage. These findings indicated that ompA may be dependent on the Caspase-1 pathway to enhance inflammation and exacerbate tissue damage. Taken together, these results confirmed a novel capsase-1-modulated mechanism underpinning ompA activity, which further reveals the NLRP3 inflammasome pathway as a potential immunomodulatory target against A. baumannii infections.

Keywords

Acinetobacter baumannii; Inflammasome; Outer membrane protein A (ompA); Pneumonia; Ubiquitin.

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