Tfp-expressing N. gonorrhoeae activates ERK (extracellular signal regulated kinase) and induces a cytoprotective state in the epithelial cell in a manner that is enhanced by pilT. As the ERK signaling pathway is well known for its role in cytoprotection and cell survival, we tested the hypothesis that ERK is involved in producing this cytoprotective effect. Inhibiting ERK activation prior to infection attenuated the ability of these bacteria to induce cytoprotection. Activated ERK specifically targeted two pro-apoptotic BH3-only proteins, Bim and Bad, for downregulation at the protein level. Bim downregulation occured through the proteasome. ERK, in addition, inactivated Bad by triggering its phosphorylation at Ser112. Finally, reducing the level of either Bad or Bim alone by siRNA was sufficient to protect uninfected cells from STS-induced apoptosis. We conclude that Tfp-induced cytoprotection is due in part to ERK-dependent modification and/or downregulation of pro-apoptotic proteins Bad and Bim.