Critical role of msgA in invasive capacity and intracellular survivability of Salmonella

Author:

Liu Xinqi1,Wang Chengzhi2ORCID,Gai Wenhua1,Sun Zhaotong1,Fang Lei2ORCID,Hua Zichun13ORCID

Affiliation:

1. State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, China

2. State Key Laboratory of Pharmaceutical Biotechnology, Jiangsu Key Laboratory of Molecular Medicine, Chemistry and Biomedicine Innovation Center, Medical School of Nanjing University, Nanjing, China

3. Changzhou High-Tech Research Institute of Nanjing University and Jiangsu Target Pharma Laboratories Inc, Changzhou, China

Abstract

ABSTRACT Salmonella enterica serovar Typhimurium, which is a common foodborne pathogen, causes both intestinal and systemic infections in hosts. Salmonella has a complex pathogenic mechanism that involves invasive capacity and intracellular survivability, which hampers research on virulence of Salmonella . The virulence of Salmonella is primarily studied through Salmonella pathogenicity islands (SPIs). However, there are also genes outside these SPIs that significantly impact virulence. Macrophage survival gene msgA is positioned at a region independent of the SPIs and conserved in Salmonella . However, there has been limited research on msgA to date. This study aims to investigate the virulent function of msgA to deepen our understanding of Salmonella virulence. Proteomic and RT-qPCR analyses reveal that MsgA influences multiple metabolic pathways and the expression of SPIs. The depletion of msgA led to the significantly reduced invasive capacity and intracellular survivability, and thus the decreased virulence of Salmonella . In conclusion, our study suggests that MsgA is an important regulator that mainly regulates virulence. Further research into the function of MsgA will enhance the understanding of Salmonella pathogenesis and promote the application of Salmonella for medical treatment. IMPORTANCE Salmonella enterica serovar Typhimurium is a common foodborne pathogen, it has a complex pathogenic mechanism that involves invasive capacity and intracellular survivability. The virulence of Salmonella is primarily studied through its pathogenicity islands. In contrast, virulence genes located outside the Salmonella pathogenicity islands (SPIs) have received less attention. Macrophage survival gene (MsgA) is positioned at a region independent of the SPIs and conserved in Salmonella . Our research indicates that MsgA is a novel global regulator influencing the metabolic pathways and SPIs. Further research into the function of MsgA will enhance the understanding of Salmonella pathogenesis and promote the application of Salmonella for medical treatment.

Funder

MOST | National Natural Science Foundation of China

JST | Natural Science Foundation of Jiangsu Province

Nanjing Municipal Science and Technology Bureau

Changzhou Municipal Science and Technology Bureau

Publisher

American Society for Microbiology

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