Bailey M J, Koronakis V, Schmoll T, Hughes C
Department of Pathology, University of Cambridge, UK.
Mol Microbiol. 1992 Apr;6(8):1003-12. doi: 10.1111/j.1365-2958.1992.tb02166.x.
Synthesis and secretion of the 110kDa haemolysin toxin of Escherichia coli and other pathogenic Gram-negative bacteria are governed by the four genes of the hly operon. We have identified, by transposon mutagenesis, an E. coli cellular locus, hlyT, required for the synthesis and secretion of haemolysin encoded in trans by intact hly operons carrying the hly upstream regulatory region. Mutation of the hlyT locus specifically reduced the level of hlyA structural gene transcript 20-100-fold and thus markedly lowered both intracellular and extracellular levels of the HlyA protein. Genetic and structural analysis of the hlyT locus mapped it at co-ordinate 3680 kbp (minute 87) on the chromosome adjacent to the fadBA operon, and identified it specifically as the rfaH (sfrB) locus which is required for transcription of the genes encoding synthesis of the sex pilus and also the lipopolysaccharide core for attachment of the O-antigen of E. coli and Salmonella. Expression of the hly operon in the E. coli hlyT mutant was restored in trans by both the hlyT and rfaH genes, suggesting that the rfaH gene is an important activator of regulon structures that are central to the fertility and virulence of these pathogenic bacteria. DNA sequencing of the hlyT locus identifies the HlyT/RfaH transcriptional activator as a protein of 162 amino acids (Mr 18325) which shows no identity to characterized transcription factors.
大肠杆菌及其他致病性革兰氏阴性菌的110kDa溶血素毒素的合成与分泌受hly操纵子的四个基因调控。我们通过转座子诱变鉴定出一个大肠杆菌细胞位点hlyT,它是由携带hly上游调控区的完整hly操纵子反式编码的溶血素合成与分泌所必需的。hlyT位点的突变使hlyA结构基因转录本水平特异性降低20至100倍,从而显著降低了HlyA蛋白的细胞内和细胞外水平。对hlyT位点的遗传和结构分析将其定位在染色体上3680kbp(87分钟)处,与fadBA操纵子相邻,并明确它就是rfaH(sfrB)位点,该位点对于编码性菌毛合成的基因以及大肠杆菌和沙门氏菌O抗原附着所需的脂多糖核心的转录是必需的。hly操纵子在大肠杆菌hlyT突变体中的表达可通过hlyT和rfaH基因反式恢复,这表明rfaH基因是这些致病细菌的育性和毒力核心调控子结构的重要激活因子。hlyT位点的DNA测序确定HlyT/RfaH转录激活因子是一种由162个氨基酸组成的蛋白质(Mr 18325),与已鉴定的转录因子没有同源性。