title: Intramacrophage Infection Reinforces the Virulence of Edwardsiella tarda.
abstract: Edwardsiella tarda is an important pathogenic bacterium that can replicate in macrophages. However, how the intramacrophage infection process affects the virulence of this bacterium is essentially unknown. Here, we show that E. tarda replicates and induces a caspase-1-dependent cell pyroptosis in a murine macrophage model. Via pyroptosis, intracellular E. tarda escapes to the extracellular milieu, forming a unique bacterial population. Being different from the bacteria cultured alone, this unique population possesses a reprogrammed transcriptional profile, particularly with upregulated type III secretion system (T3SS)/T6SS cluster genes. Subsequent studies revealed that the macrophage-released population gains enhanced infectivity for host epithelial cells and increases resistance to multiple host defenses and hence displays significantly promoted virulence in vivo Further studies indicated that T3SS is essentially required for the macrophage infection process, while T6SS contributes to infection-induced bacterial virulence. Altogether, this work demonstrates that E. tarda can utilize macrophages as a niche for virulence priming and for spreading infection, suggesting a positive role for intramacrophage infection in bacterial pathogenesis.
  
  
  
  Many pathogens can replicate in macrophages, which is crucial for their pathogenesis. To survive in the macrophage cell, pathogens are likely to require fitness genes to counteract multiple host-killing mechanisms. Here, Edwardsiella tarda is proved to exit from macrophages during infection. This macrophage-released population displays a reprogrammed transcriptional profile with significantly upregulated type III secretion system (T3SS)/T6SS-related genes. Furthermore, both enhanced infectivity in epithelial cells and activated resistance to complex host defenses were conferred on this macrophage-primed population, which consequently promoted the full virulence of E. tarda in vivo Our work provides evidence that E. tarda can utilize macrophages as a niche for virulence priming and for spreading infection, highlighting the importance of the intramacrophage infection cycle for the pathogenesis of E. tarda.
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
authors.forename: Lingzhi
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
authors.forename: Chunshan
authors.initials: C
authors.lastname: Ni
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
authors.forename: Wenting
authors.initials: W
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
authors.forename: Tongcheng
authors.initials: T
authors.lastname: Dai
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
authors.forename: Dahai
authors.initials: D
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China Shanghai Engineering Research Center of Maricultured Animal Vaccines, Shanghai, China.
authors.forename: Qiyao
authors.initials: Q
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China Shanghai Engineering Research Center of Maricultured Animal Vaccines, Shanghai, China.
authors.forename: Yuanxing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China Shanghai Engineering Research Center of Maricultured Animal Vaccines, Shanghai, China qinliu@ecust.edu.cn.
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
mesh_terms: D000818:Animals; D002460:Cell Line; D020609:Edwardsiella tarda / Q000235:genetics / Q000472:pathogenicity*; D015964:Gene Expression Regulation, Bacterial; D006367:HeLa Cells; D006801:Humans; D008264:Macrophages / Q000166:cytology* / Q000382:microbiology*; D051379:Mice; D000069292:Pyroptosis; D000069296:Type III Secretion Systems / Q000235:genetics*; D000069376:Type VI Secretion Systems / Q000235:genetics*; D015854:Up-Regulation; D014774:Virulence
chemical_list: D000069296:Type III Secretion Systems; D000069376:Type VI Secretion Systems