Schmerk Crystal L, Duplantis Barry N, Howard Perry L, Nano Francis E
Department of Biochemistry and Microbiology, University of Victoria, Victoria, BC, Canada.
Department of Biology, University of Victoria, Victoria, BC, Canada.
Microbiology (Reading). 2009 May;155(Pt 5):1498-1504. doi: 10.1099/mic.0.025445-0. Epub 2009 Apr 16.
Several genes contained in the Francisella pathogenicity island (FPI) encode proteins needed for intracellular growth and virulence of Francisella tularensis. The pdpA gene is the first cistron in the larger of the two operons found in the FPI. In this work we studied the intracellular growth phenotype of a Francisella novicida mutant in the pdpA gene. The DeltapdpA strain was capable of a small amount of intracellular replication but, unlike wild-type F. novicida, remained associated with the lysosomal marker LAMP-1, suggesting that PdpA is necessary for progression from the early phagosome phase of infection. Strains with in cis complementation of the DeltapdpA lesion showed a restoration of intracellular growth to wild-type levels. Infection of macrophages with the DeltapdpA mutant generated a host-cell mRNA profile distinct from that generated by infection with wild-type F. novicida. The transcriptional response of the host macrophage indicates that PdpA functions directly or indirectly to suppress macrophage ability to signal via growth factors, cytokines and adhesion ligands.
土拉弗朗西斯菌致病岛（FPI）中包含的几个基因编码土拉弗朗西斯菌细胞内生长和毒力所需的蛋白质。pdpA基因是在FPI中发现的两个操纵子中较大的那个操纵子的第一个顺反子。在这项研究中，我们研究了pdpA基因中土拉弗朗西斯菌新凶手亚种突变体的细胞内生长表型。ΔpdpA菌株能够进行少量的细胞内复制，但与野生型土拉弗朗西斯菌新凶手亚种不同，它仍与溶酶体标记物LAMP-1相关联，这表明PdpA对于从感染的早期吞噬体阶段进展是必需的。对ΔpdpA损伤进行顺式互补的菌株显示细胞内生长恢复到野生型水平。用ΔpdpA突变体感染巨噬细胞产生的宿主细胞mRNA谱与用野生型土拉弗朗西斯菌新凶手亚种感染产生的不同。宿主巨噬细胞的转录反应表明，PdpA直接或间接发挥作用，抑制巨噬细胞通过生长因子、细胞因子和粘附配体发出信号的能力。
