The contribution of LepA to virulence and host cell invasion in Salmonella Typhimurium

Background LepA is one of the most conserved proteins and is found in nearly all bacteria as well as in eukaryotes. Mutation of lepA increases antibiotic tolerance in Escherichia coli , Salmonella , and rifampicin-resistant clinical mycobacterial isolates. However, the physiological function and its role in virulence of LepA remain elusive, particularly considering that LepA is non-essential under laboratory conditions. Methods We investigated the lepA gene of Salmonella Typhimurium for its role in bacterial invasion of host cells. Invasion assays using lepA mutants were performed in macrophages (J774) and epithelial cells (Caco-2 and HT29-MTX), both in the presence and absence of mucus. In addition, virulence gene induction, motility, and pathogenicity in a Galleria mellonella infection model were assessed. Results The lepA deletion strain showed reduced invasion in all cell types regardless of mucus, indicating its essential role in the invasion process and in the initial survival within macrophages. Deletion of lepA also resulted in decreased induction of virulence-associated genes and reduced pathogenicity in Galleria mellonella . Conclusion These findings provide important insights into the molecular determinants of Salmonella Typhimurium virulence and contribute to a deeper understanding of the conservation of LepA across organisms.