Stibitz S
Division of Bacterial Products, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, Maryland 20892.
J Bacteriol. 1994 Sep;176(18):5615-21. doi: 10.1128/jb.176.18.5615-5621.1994.
By using chemical mutagenesis and genetic mapping, a search was undertaken for previously undescribed genes which may be involved in different regulatory mechanisms governing different virulence factors of Bordetella pertussis. Previous studies have shown that the fha locus encoding filamentous hemagglutinin is regulated directly by the bvgAS two component system, while regulation of ptx encoding pertussis toxin is less direct or occurs by a different mechanism. With a strain containing gene fusions to each of these regulated loci, screening was done for mutations which were defective for ptx expression but maintained normal or nearly normal levels of fha expression. Two mutations which had such a phenotype and were also deficient in adenylate cyclase toxin/hemolysin expression were found and characterized more fully. Both were found to affect residues in the C-terminal portion of the BvgA response regulator protein, a domain which shares sequence similarity with a family of regulatory proteins including FixJ, UhpA, MalT, RcsA, RcsB, and LuxR. The residues affected are within a region which, by extension from studies on the LuxR protein, may be involved in transcriptional activation.
通过化学诱变和基因定位，对可能参与调控百日咳博德特氏菌不同毒力因子的不同调控机制的先前未描述基因进行了搜索。先前的研究表明，编码丝状血凝素的fha位点直接受bvgAS双组分系统调控，而编码百日咳毒素的ptx的调控则不太直接或通过不同机制发生。利用与这些受调控位点各自基因融合的菌株，对ptx表达有缺陷但fha表达维持正常或接近正常水平的突变进行了筛选。发现了两个具有这种表型且腺苷酸环化酶毒素/溶血素表达也缺陷的突变，并对其进行了更全面的表征。两者都被发现影响BvgA应答调节蛋白C末端部分的残基，该结构域与包括FixJ、UhpA、MalT、RcsA、RcsB和LuxR在内的一类调节蛋白具有序列相似性。受影响的残基位于一个区域内，根据对LuxR蛋白的研究推断，该区域可能参与转录激活。
