title: Inhibition of macrophage autophagy induced by Salmonella enterica serovar typhi plasmid.
abstract: pR(ST98), a chimeric plasmid isolated from Salmonella enterica serovar typhi (S. typhi), is involved in bacterial multidrug-resistance and virulence, however, its exact contributions to bacterial pathogenesis are still not fully understood. To investigate whether pR(ST98) exhibits potential to mediate macrophage autophagy and apoptosis, murine macrophage-like cell line (J774A.1) was infected with wild type strain (S. typhi-WT), mutant strain (S. typhi-DeltapR(ST98)) and complement of S. typhi-DeltapR(ST98) (S. typhi-c-pR(ST98)). Results revealed that S. typhi harboring pR(ST98) decreased the number of autophagy vacuoles of macrophages as well as the expression of Beclin 1 and LC3-II at the early stage of infection; apoptosis rate of macrophages infected with S. typhi-DeltapR(ST98) was lower than that infected with S. typhi-WT or S. typhi-c-pR(ST98). The survival rate of intracellular bacteria carrying pR(ST98) was much higher than that of plasmid free strain. After intervention with autophagy agonist rapamycin, apoptosis rate of the cells infected with S. typhi containing pR(ST98) and intracellular bacterial growth decreased. Our study suggested that pR(ST98) could inhibit autophagy and induce cell apoptosis for the host bacterial survival and proliferation.
authors.affiliation: Medical College of Soochow University, No. 199, Ren Ai Road, Suzhou, Jiangsu 215123, P. R. China.
authors.forename: ShuYan
authors.initials: S
authors.lastname: Wu
authors.affiliation: Medical College of Soochow University, No. 199, Ren Ai Road, Suzhou, Jiangsu 215123, P. R. China.
authors.forename: YuanYuan
authors.initials: Y
authors.lastname: Chu
authors.affiliation: Medical College of Soochow University, No. 199, Ren Ai Road, Suzhou, Jiangsu 215123, P. R. China.
authors.forename: YanRu
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Medical College of Soochow University, No. 199, Ren Ai Road, Suzhou, Jiangsu 215123, P. R. China.
authors.forename: YuanYuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Medical College of Soochow University, No. 199, Ren Ai Road, Suzhou, Jiangsu 215123, P. R. China.
authors.forename: PeiYan
authors.initials: P
authors.lastname: He
authors.affiliation: Medical College of Soochow University, No. 199, Ren Ai Road, Suzhou, Jiangsu 215123, P. R. China.
authors.forename: YaJie
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Medical College of Soochow University, No. 199, Ren Ai Road, Suzhou, Jiangsu 215123, P. R. China.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Medical College of Soochow University, No. 199, Ren Ai Road, Suzhou, Jiangsu 215123, P. R. China.
authors.forename: QiuChen
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Medical College of Soochow University, No. 199, Ren Ai Road, Suzhou, Jiangsu 215123, P. R. China.
authors.forename: Ling
authors.initials: L
authors.lastname: Han
authors.affiliation: Medical College of Soochow University, No. 199, Ren Ai Road, Suzhou, Jiangsu 215123, P. R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Huang
mesh_terms: D000818:Animals; D001343:Autophagy; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D046529:Microscopy, Electron, Transmission; D010957:Plasmids; D016133:Polymerase Chain Reaction; D019779:Salmonella enterica / Q000502:physiology* / Q000648:ultrastructure
chemical_list: D017931:DNA Primers