Zhao, MingnaZhang, LingfeiLv, ShaogangZhang, ChenziWang, LinChen, HongZhou, YanLou, Jiatao2017-06-152017Zhao, Mingna, Lingfei Zhang, Shaogang Lv, Chenzi Zhang, Lin Wang, Hong Chen, Yan Zhou, and Jiatao Lou. 2017. “IQGAP1 Mediates Hcp1-Promoted Escherichia coli Meningitis by Stimulating the MAPK Pathway.” Frontiers in Cellular and Infection Microbiology 7 (1): 132. doi:10.3389/fcimb.2017.00132. http://dx.doi.org/10.3389/fcimb.2017.00132.http://nrs.harvard.edu/urn-3:HUL.InstRepos:33029899Escherichia coli-induced meningitis remains a life-threatening disease despite recent advances in the field of antibiotics-based therapeutics, necessitating continued research on its pathogenesis. The current study aims to elucidate the mechanism through which hemolysin-coregulated protein 1 (Hcp1) induces the apoptosis of human brain microvascular endothelial cells (HBMEC). Co-immunoprecipitation coupled with mass spectrometric (MS) characterization led to the identification of IQ motif containing GTPase activating protein 1 (IQGAP1) as a downstream target of Hcp1. IQGAP1 was found to be up-regulated by Hcp1 treatment and mediate the stimulation of HBMEC apoptosis. It was shown that Hcp1 could compete against Smurf1 for binding to IQGAP1, thereby rescuing the latter from ubiquitin-dependent degradation. Subsequent study suggested that IQGAP1 could stimulate the MAPK signaling pathway by promoting the phosphorylation of ERK1/2, an effect that was blocked by U0126, an MAPK inhibitor. Furthermore, U0126 also demonstrated therapeutic potential against E. coli meningitis in a mouse model. Taken together, our results suggested the feasibility of targeting the MAPK pathway as a putative therapeutic strategy against bacterial meningitis.en-USIQGAP1HCP1meningitisMAPK pathwayJournal Article2017-06-1510.3389/fcimb.2017.00132