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.