Fig. 6
Proposed Model. Left: a Control cells undergo DNA replication where RPA protects ssDNA from breakage. b Cells divide, and c no senescence is observed, which impairs Salmonella infection. Right: d The typhoid toxin causes an initial burst of DNA damage in G1 that combines with damage in S-phase to cause replication stress by oversupply of the RPA substrate ssDNA. e RPA sequestration causes DNA damage that manifests as γH2AX RINGs. f RING cells enter into a senescence-like state resulting in SASP-induced transmissible senescence that promotes Salmonella invasion into host cells. Thus, toxin manipulation of infection niches via senescence may contribute to chronic Salmonella infections, which are associated with the typhoid toxin14,16,57
