Virulence factors and mechanisms of paediatric pneumonia caused by Enterococcus faecalis

Zhiying Tian; Asif Iqbal Khan; Ata Ur Rehman; Ting Deng; Chao Ma; Liang Wang

doi:10.1186/s13099-022-00522-z

Virulence factors and mechanisms of paediatric pneumonia caused by Enterococcus faecalis

Gut Pathog. 2023 Jan 9;15(1):2. doi: 10.1186/s13099-022-00522-z.

Authors

Zhiying Tian¹, Asif Iqbal Khan¹, Ata Ur Rehman¹, Ting Deng¹, Chao Ma¹, Liang Wang²

Affiliations

¹ Laboratory of Biochemistry and Molecular Biology, Department of Biotechnology, College of Basic Medicine, Dalian Medical University, Dalian, China.
² National Joint Engineering Laboratory, Regenerative Medicine Centre, Stem Cell Clinical Research Centre, The First Affiliated Hospital of Dalian Medical University, Dalian, China. wangliang@dmu.edu.cn.

Abstract

Paediatric pneumonia is a respiratory infection that affects infants and young children under the age of 3. This disease is the leading cause of infant and child mortality in developing countries because of the weak immune system of young children. The difficulty and length of time required to identify the pathogen and causative agent are the main reasons for this high mortality rate. In addition, the identification of certain causative agents is particularly important for the treatment of paediatric pneumonia. In this study, we explored the possible mechanisms by which pathogenic Enterococcus faecalis induced pneumonia in vivo. The potential virulence factors of bacteria isolated from the intestines of paediatric pneumonia patients were determined. Taken together, the results suggested that lysophosphatidic acid (LTA) from pathogenic E. faecalis decreases the expression of platelet-activating factor receptor (PAFR), which in turn disrupts the function of intestinal tight junctions (Occ and Ccldn1), leading to the entry of LE-LTA into the bloodstream because of the disruption of the intestinal barrier. Although LTA can enter circulation, it cannot directly infiltrate the lungs, which indicates that lung inflammation in mice is not caused by the direct entry of LE-LTA into the lungs. We further found that LTA activates immune cells, such as CD8 + T cells and type 2 innate lymphocytes, in vivo. Interleukin-6 and interleukin-17 can produce large amounts of inflammatory factors and thus promote the development of pneumonia. In conclusion, our findings demonstrate that the LTA of pathogenic E. faecalis in the intestine is a virulence factor that can cause paediatric pneumonia. This study found that intestinal bacterial virulence factors can induce immune responses in the lungs and blood. These findings could provide further insight into the mechanism of infectious diseases in the lung that are caused by bacteria in the intestine.

Keywords: Enterococcus faecalis; Lipoteichoic acid; Paediatric pneumonia; Type 2 innate lymphocyte; Virulence factor.