Streptococcus pneumoniae aminopeptidase N contributes to bacterial virulence and elicits a strong innate immune response through MAPK and PI3K/AKT signaling

Ling Wang; Xuemei Zhang; Guangying Wu; Yuhong Qi; Jinghui Zhang; Jing Yang; Hong Wang; Wenchun Xu

doi:10.1007/s12275-020-9538-0

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Streptococcus pneumoniae aminopeptidase N contributes to bacterial virulence and elicits a strong innate immune response through MAPK and PI3K/AKT signaling: Ling Wang , Xuemei Zhang , Guangying Wu , Yuhong Qi , Jinghui Zhang , Jing Yang , Hong Wang , Wenchun Xu; Journal of Microbiology 2020;58(4):330-339.
DOI: https://doi.org/10.1007/s12275-020-9538-0
Published online: February 27, 2020

Key Laboratory of Clinical Laboratory Diagnostics Designated by the Ministry of Education, School of Laboratory Medicine, Chongqing Medical University, Chongqing, P. R. ChinaKey Laboratory of Clinical Laboratory Diagnostics Designated by the Ministry of Education, School of Laboratory Medicine, Chongqing Medical University, Chongqing, P. R. China

Corresponding author: Wenchun Xu , Tel: +86-023-68485239,

Received: 8 November 2019 • Revised: 26 December 2019 • Accepted: 20 January 2020

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Abstract

Streptococcus pneumoniae is a Gram-positive pathogen with high morbidity and mortality globally but some of its pathogenesis remains unknown. Previous research has provided evidence that aminopeptidase N (PepN) is most likely a virulence factor of S. pneumoniae. However, its role in S. pneumoniae virulence and its interaction with the host remains to be confirmed. We generated a pepN gene deficient mutant strain and found that its virulence for mice was significantly attenuated as were in vitro adhesion and invasion of host cells. The PepN protein could induce a strong innate immune response in vivo and in vitro and induced secretion of IL-6 and TNF-α by primary peritoneal macrophages via the rapid phosphorylation of MAPK and PI3K/AKT signaling pathways and this was confirmed using specific pathway inhibitors. In conclusion, PepN is a novel virulence factor that is essential for the virulence of S. pneumoniae and induces host innate immunity via MAPK and PI3K/AKT signaling.

Keywords: Streptococcus pneumoniae;PepN;virulence;innate immunity;signaling pathway

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Streptococcus pneumoniae aminopeptidase N contributes to bacterial virulence and elicits a strong innate immune response through MAPK and PI3K/AKT signaling

J. Microbiol. 2020;58(4):330-339. Published online February 27, 2020

DOI: https://doi.org/10.1007/s12275-020-9538-0

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