Lipid droplet accumulation occurs early following Salmonella infection and contributes to intracellular bacterial survival and replication.

Souza, Ellen Kiarely; Pereira-Dutra, Filipe S.; Rajão, Matheus A.; Ferraro-Moreira, Felipe; Goltara-Gomes, Taynná C.; Cunha-Fernandes, Tamires; Santos, Julia da Cunha; Prestes, Elisa B.; Andrade, Warrison A.; Zamboni, Dario S.; Bozza, Marcelo T.; Bozza, Patrícia T.

Salmonellosis is a public health problem caused by Salmonella sp., a highly adapted facultative intracellular pathogen. After internalization, Salmonella sp. Manipulates several host processes, mainly through the activation of the type III secretion system (T3SS), including modification of host lipid metabolism and lipid droplet (LD) accumulation. LDs are dynamic and complex lipid-rich organelles involved in several cellular processes. The present study investigated the mechanism involved in LD biogenesis in Salmonella-infected macrophages and its role in bacterial pathogenicity. Here, we reported that S. Typhimurium induced a rapid time- dependent increase of LD formation in macrophages. The LD biogenesis was demonstrated to depend on Salmonella's viability and SPI1-related T3SS activity, with the participation of Toll-Like Receptor (TLR) signaling. We also observed that LD accumulation occurs through TLR2-dependent signaling and is counter-regulated by TLR4. Last, the pharmacologic modulation of LD formation by inhibiting diacylglycerol O-acyltransferase 1 (DGAT1) and cytosolic phospholipase A2 (cPLA2) significantly reduced the intracellular bacterial proliferation and impaired the prostaglandin E2 (PGE2) synthesis. Collectively, our data suggest the role of LDs on S. typhimurium intracellular survival and replication in macrophages. This data set provides new perspectives for future investigations about LDs in host--pathogen interaction.

SALMONELLA diseases; LIPID metabolism; PHOSPHOLIPASE A2; LIPIDS; INTRACELLULAR pathogens; TOLL-like receptors; SALMONELLA; SALMONELLA enterica

Molecular Microbiology, 2022, Vol 117, Issue 2, p293

0950-382X

Academic Journal

10.1111/mmi.14844