Effect of msbB knockout on gene expression of Salmonella enterica subsp. enterica serovar Typhimurium str. 14028S

The Salmonella enterica serovar Typhimurium (ST) mutant lacking the msbB gene (?msbB) has been widely studied as a candidate for attenuated bacterial vectors in therapeutic applications. Deletion of msbB results in LPS with under-acylated lipid A, which lowers endotoxicity while maintaining structural integrity. This attenuation has traditionally been attributed to reduced TLR4 activation due to weaker interaction between the modified lipid A and TLR4. In our study, we confirmed that ?msbB ST was less lethal than wild-type (WT) ST in a mouse sepsis model. However, this difference persisted even in TLR4- and caspase-11-deficient mice, suggesting that LPS signaling is not the primary determinant of virulence. In vitro, bone marrow–derived macrophages (BMDMs) from TLR4- or caspase-11-deficient mice showed only modest reductions in ST-induced cell death and cytokine production. Importantly, ?msbB ST behaved similarly to WT ST in these assays, further indicating that LPS-mediated signaling is not central to the observed attenuation. Additionally, the mutant exhibited increased outer membrane permeability, likely contributing to its heightened antibiotic sensitivity—and reduced motility due to lower flagellin protein levels. Overall design: RNAseq profiling of wildtype ST and ST-?msbB, two samples cultured from two different colony of each strain were sent for sequencing