AUTHOR=Wang Ming , Xiong Dan , Wang Xinwei , Gu Dan , Meng Chuang , Jiao Xinan , Pan Zhiming 

TITLE=The DNA adenine methylase of Salmonella Enteritidis promotes their intracellular replication by inhibiting arachidonic acid metabolism pathway in macrophages

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1080851

DOI=10.3389/fmicb.2023.1080851

ISSN=1664-302X

ABSTRACT=Macrophages can participate in immune responses by altering their metabolism, and play important roles in controlling bacterial infections. However, Salmonella Enteritidis can survive and proliferate in macrophages. We found that dam gene could promote the invasion and proliferation of macrophages by Salmonella Enteritidis, and inhibit the secretion of IL-1β and IL-6. Through non-targeted metabolomics, we found that Salmonella Enteritidis could regulate the metabolism of macrophages, and the dam gene of Salmonella Enteritidis can regulate fatty acid-related metabolic pathways in macrophage. Using fatty acid targeting metabolomics, we found that dam gene of Salmonella Enteritidis had significant effects on arachidonic acid and related metabolic pathways in macrophages. The dam gene can promote the proliferation of Salmonella Enteritidis in macrophages by inhibiting the metabolic pathway of cytosolic phospholipase A2-mediated arachidonic acid production and conversion to prostaglandin E2 in macrophages, reducing the secretion of the pro-inflammatory factors IL-1β and IL-6, leading to immune escape. In addition, inhibition of arachidonic acid-related pathways in macrophages by Arachidonyl trifluoromethyl ketone could restore the proliferation of dam gene deletion strains in macrophages. This study explored the role of dam genes in the process of Salmonella Enteritidis invading host cells from the perspective of host cell metabolism, and provides new insights into the immune escape mechanism of Salmonella Enteritidis.