文献类型：期刊文献

英文题名：Intramacrophage Infection Reinforces the Virulence of Edwardsiella tarda

作者：Zhang, Lingzhi[1];Ni, Chunshan[1];Xu, Wenting[1];Dai, Tongcheng[1];Yang, Dahai[1];Wang, Qiyao[1,2];Zhang, Yuanxing[1,2];Liu, Qin[1,2]

机构：[1]E China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[2]Shanghai Engn Res Ctr Maricultured Anim Vaccines, Shanghai, Peoples R China

年份：2016

卷号：198

期号：10

起止页码：1534

外文期刊名：JOURNAL OF BACTERIOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000375075600008)】；

基金：This work, including the efforts of Qin Liu, was funded by National High Technology Research and Development Program of China (2013AA093101). This work, including the efforts of Qin Liu, was funded by National Natural Science Foundation of China (NSFC) (31430090 and 31472308).

语种：英文

摘要：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. IMPORTANCE 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.