Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa 920-1192, Japan;
J Immunol. 2014 Jan 15;192(2):666-75. doi: 10.4049/jimmunol.1300968. Epub 2013 Dec 13.
Bacteria adapt themselves to host environments by altering the pattern of gene expression. The promoter-recognizing subunit σ of bacterial RNA polymerase plays a major role in the selection of genes to be transcribed. Among seven σ factors of Escherichia coli, σ(38) is responsible for the transcription of genes in the stationary phase and under stressful conditions. We found a transient increase of σ(38) when E. coli was injected into the hemocoel of Drosophila melanogaster. The loss of σ(38) made E. coli rapidly eliminated in flies, and flies infected with σ(38)-lacking E. coli stayed alive longer than those infected with the parental strain. This was also observed in fly lines defective in humoral immune responses, but not in flies in which phagocytosis was impaired. The lack of σ(38) did not influence the susceptibility of E. coli to phagocytosis, but made them vulnerable to killing after engulfment. The changes caused by the loss of σ(38) were recovered by the forced expression of σ(38)-encoding rpoS as well as σ(38)-regulated katE and katG coding for enzymes that detoxify reactive oxygen species. These results collectively suggested that σ(38) contributes to the prolonged survival of E. coli in Drosophila by inducing the production of enzymes that protect bacteria from killing in phagocytes. Considering the similarity in the mechanism of innate immunity against invading bacteria between fruit flies and humans, the products of these genes could be new targets for the development of more effective antibacterial remedies.
细菌通过改变基因表达模式来适应宿主环境。细菌 RNA 聚合酶的启动子识别亚基 σ在基因转录的选择中起着主要作用。在大肠杆菌的 7 种 σ 因子中,σ(38)负责转录静止期和应激条件下的基因。当大肠杆菌被注射到黑腹果蝇的血腔中时,我们发现 σ(38)会短暂增加。σ(38)缺失使大肠杆菌在果蝇中迅速被清除,而感染缺乏 σ(38)大肠杆菌的果蝇比感染亲本菌株的果蝇存活时间更长。在体液免疫反应缺陷的果蝇系中观察到了这种情况,但在吞噬作用受损的果蝇中没有观察到这种情况。σ(38)缺失并不影响大肠杆菌对吞噬作用的易感性,但使它们在吞噬后容易被杀死。缺失 σ(38)引起的变化可以通过强制表达编码 rpoS 的 σ(38)以及编码解毒活性氧物质的 katE 和 katG 酶的 σ(38)调节来恢复。这些结果共同表明,σ(38)通过诱导产生保护细菌免受吞噬细胞杀伤的酶,促进大肠杆菌在果蝇中的存活时间延长。考虑到果蝇和人类之间针对入侵细菌的先天免疫机制的相似性,这些基因的产物可能成为开发更有效的抗菌疗法的新靶点。