Zhou Lian, Wang Jing, Zhang Lian-Hui
Institute of Molecular and Cell Biology, Singapore, Singapore.
PLoS One. 2007 Dec 12;2(12):e1291. doi: 10.1371/journal.pone.0001291.
Many gram-negative bacterial pathogens employ Type III secretion systems (T3SS) to inject effector proteins into host cells in infectious processes.
METHODOLOGY/PRINCIPAL FINDINGS: By screening a transposon mutant library of P. aeruginosa, we found that mutation of spuDEFGH, which encode a major spermidine uptake system, abolished the expression of the exsCEBA operon that codes for key T3SS regulators under inducing conditions (low calcium). Whole genome microarray analysis revealed that inactivation of the spermidine uptake system significantly decreased the transcriptional expression of most, if not all, T3SS genes. Consistently, the spermidine uptake mutants showed decreased expression of the T3SS genes in responding to host cell extract and attenuated cytotoxicity. Furthermore, exogenous addition of spermidine to the wild type strain PAO1 enhanced the expression of exsCEBA and also the effector protein genes.
CONCLUSION/SIGNIFICANCE: Cumulatively, these data have depicted a novel spermidine transporter-dependent signaling pathway, which appears to play an essential role in modulation of T3SS expression in P. aeruginosa.
许多革兰氏阴性细菌病原体在感染过程中利用III型分泌系统(T3SS)将效应蛋白注入宿主细胞。
方法/主要发现:通过筛选铜绿假单胞菌的转座子突变体文库,我们发现编码主要亚精胺摄取系统的spuDEFGH发生突变后,在诱导条件下(低钙),编码关键T3SS调节因子的exsCEBA操纵子的表达被消除。全基因组微阵列分析表明,亚精胺摄取系统的失活显著降低了大多数(如果不是全部)T3SS基因的转录表达。一致地,亚精胺摄取突变体在对宿主细胞提取物的反应中显示出T3SS基因表达降低,并且细胞毒性减弱。此外,向野生型菌株PAO1外源添加亚精胺可增强exsCEBA以及效应蛋白基因的表达。
结论/意义:总体而言,这些数据描绘了一条新的依赖亚精胺转运体的信号通路,该通路似乎在铜绿假单胞菌T3SS表达的调节中起重要作用。