B Cells as a Host of Persistent <scp><i>Salmonella Typhimurium</i></scp>

Salmonella enterica serovar Typhimurium (S. Tm) can colonise different intracellular niches, either actively dividing or remaining dormant to persist. Bacterial persisters are phenotypic variants that temporarily enter a nonreplicative state. This allows them to evade host cell defences and antibiotics, leading to chronic infections. We previously reported that during chronic periods, Salmonella remains within B cells in the bone marrow and spleen. However, the dynamics of Salmonella replication and the formation of antibiotic tolerance in infected B cells have not been studied. Here we show that B cells are a favourable reservoir for bacterial persistence. In vitro and in vivo experiments identified non-replicating, persistent Salmonella subsets in splenic B cells. These non-replicative Salmonella are tolerant to antibiotics (cefotaxime and ciprofloxacin), while replicative bacteria remain susceptible. Infected mice demonstrated viable, nonreplicative Salmonella in spleen B cells, maintaining antibiotic tolerance. Although acid intravacuolar pH and SPI-2 regulators (SsrA/SsrB) are not necessary for Salmonella persistence in B cells, the SehA/B and RelE/B toxin-antitoxin system facilitates the formation of the persistent phenotype in Salmonella. Overall, we show that B cells are a reservoir for nonreplicating, antibiotic-tolerant Salmonella.