B Cells as a Host of Persistent Salmonella Typhimurium

ABSTRACT 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 .