Regulation and physiological significance of ClpC and ClpP in Streptococcus mutans
Regulation and physiological significance of ClpC and ClpP in Streptococcus mutans
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DOI：
10.1128/jb.184.22.6357-6366.2002
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发表时间：
2002-11-01
影响因子：
3.2
通讯作者：
Burne, RA
中科院分区：
文献类型：
--
作者：
Lemos, JAC;Burne, RA
变形链球菌对环境胁迫，特别是低pH值的耐受性是该微生物毒力的核心。CLP ATPase通过其蛋白的再激活和重塑活性，以及其靶向错误折叠的蛋白质被ClpP肽酶降解的能力，参与了对压力的耐受和反应的调节。这项研究的目的是剖析选定的CLP基因在变形链球菌应激反应中的作用，特别是耐酸性和适应性。在变形链球菌基因组中发现了ClpB、clpC、clpe、clp1、clpX和ClpP基因的同源物。选择ClpC和ClpP作为研究的重点，在低pH和40℃以上的生长条件下进行诱导表达。CtsR是clpC操纵子中两个基因中的第一个，它的失活表明ctsR是CLP和Groes-EL基因表达的抑制因子。缺乏ClpP的菌株，但不缺乏ClpC的菌株，其在胁迫诱导条件下的生长能力受到损害，形成长链，在培养中聚集，降低了遗传转化效率，并降低了形成生物膜的能力。对野生型细胞和ctsR和ClpP突变体的二维蛋白质凝胶进行比较，发现蛋白质表达模式发生了许多变化。特别是，在ClpP突变体中，GroESL和DNAK的产量增加，这表明细胞受到压力，可能是由于变性蛋白的积累。
Tolerance of environmental stress, especially low pH, by Streptococcus mutans is central to the virulence of this organism. The Clp ATPases are implicated in the tolerance of, and regulation of the response to, stresses by virtue of their protein reactivation and remodeling activities and their capacity to target misfolded proteins for degradation by the ClpP peptidase. The purpose of this study was to dissect the role of selected clp genes in the stress responses of S. mutans, with a particular focus on acid tolerance and adaptation. Homologues of the clpB, clpC, clpE, clpL, clpX, and clpP genes were identified in the S. mutans genome. The expression of clpC and clpP, which were chosen as the focus of this study, was induced at low pH and at growth above 40degreesC. Inactivation of ctsR, the first of two genes in the clpC operon, demonstrated that CtsR acts as a repressor of clp and groES-EL gene expression. Strains lacking ClpP, but not strains lacking ClpC, were impaired in their ability to grow under stress-inducing conditions, formed long chains, aggregated in culture, had reduced genetic transformation efficiencies, and had a reduced capacity to form biofilms. Comparison of two-dimensional protein gels from wild-type cells and the ctsR and clpP mutants revealed many changes in the protein expression patterns. In particular, in the clpP mutant, there was an increased production of GroESL and DnaK, suggesting that cells were stressed, probably due to the accumulation of denatured proteins.