Krafft A E, Tai S P, Coker C, Holmes R K
Department of Microbiology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814.
Microb Pathog. 1992 Aug;13(2):85-92. doi: 10.1016/0882-4010(92)90069-z.
The production of diphtheria toxin (DT) by Corynebacterium diphtheriae C7 (beta) is transcriptionally regulated by the iron-dependent diphtheria toxin repressor, DtxR. Transcription of the tox gene was studied in wild-type C. diphtheriae C7 (beta) and in lysogens carrying mutants of beta that determine insensitivity to inhibition of DT production by iron. Under low iron conditions in all strains, tox-specific mRNA appeared and DT production began during late-log phase, and they increased to maximal levels at stationary phase. Under high iron conditions, tox-specific mRNA and DT production were strongly repressed in C7 (beta) but only partially repressed in C7 (beta tox-202) and C7 (beta tox-201). Under high and low iron conditions, DT production and tox-specific mRNA levels were greater in C7 (beta tox-201) and C7 (beta tox-202) than in wild-type C7 (beta). Addition of iron or rifampicin to low iron cultures of C. diphtheriae C7 (beta) repressed tox-mRNA production promptly and with a similar time course. In contrast, repression of tox-mRNA synthesis in C. diphtheriae C7 (beta tox-201) occurred promptly after addition of rifampicin but more slowly after addition of iron. Nucleotide sequence analysis revealed single G to A mutations at positions -47 and -48, within the preferred '-10' sequence of the tox promoter, in beta tox-201 and beta tox-202, respectively. The single nucleotide substitutions in the tox-201 and tox-202 regulatory alleles, therefore, have pleiotropic effects, causing increased activity of the promoter and partial resistance of the operator to iron-dependent repression.
白喉棒状杆菌C7（β）产生白喉毒素（DT）的过程受到铁依赖性白喉毒素阻遏物DtxR的转录调控。在野生型白喉棒状杆菌C7（β）以及携带β突变体的溶原菌中研究了tox基因的转录情况，这些β突变体决定了对铁抑制DT产生的不敏感性。在所有菌株的低铁条件下，tox特异性mRNA出现，DT产生在对数后期开始，并在稳定期增加到最大水平。在高铁条件下，tox特异性mRNA和DT产生在C7（β）中受到强烈抑制，但在C7（β tox - 202）和C7（β tox - 201）中仅部分受到抑制。在高铁和低铁条件下，C7（β tox - 201）和C7（β tox - 202）中的DT产生和tox特异性mRNA水平高于野生型C7（β）。向白喉棒状杆菌C7（β）的低铁培养物中添加铁或利福平会迅速抑制tox - mRNA的产生，且时间进程相似。相比之下，在白喉棒状杆菌C7（β tox - 201）中添加利福平后tox - mRNA合成迅速受到抑制，但添加铁后抑制作用较慢。核苷酸序列分析显示，在tox启动子的优选“-10”序列内，β tox - 201和β tox - 202分别在-47和-48位发生了单个G到A的突变。因此，tox - 201和tox - 202调控等位基因中的单核苷酸取代具有多效性，导致启动子活性增加以及操纵基因对铁依赖性阻遏的部分抗性。
