Present address: Department of Microbiology and Molecular Genetics, McGovern Medical School, Houston, Texas, USA.
Department of Microbiology, Molecular Genetics and Immunology, University of Kansas Medical Center, Kansas City, KS, USA.
Microbiology (Reading). 2020 Jul;166(7):641-653. doi: 10.1099/mic.0.000920.
is one of the major bacteria of the human oral cavity that is associated with dental caries. The pathogenicity of this bacterium is attributed to its ability to rapidly respond and adapt to the ever-changing conditions of the oral cavity. The major player in this adaptive response is ClpP, an intracellular protease involved in degradation of misfolded proteins during stress responses. encodes a single gene with an upstream region uniquely containing multiple tandem repeat sequences (RSs). Here, we explored expression of with respect to various stresses and report some new findings. First, we found that at sub-inhibitory concentration, certain cell-wall damaging antibiotics were able to induce expression. Specifically, third- and fourth-generation cephalosporins that target penicillin-binding protein 3 (PBP3) strongly enhanced the expression. However, induction of was weak when the first-generation cephalosporins with lower affinity to PBP3 were used. Surprisingly, carbapenems, which primarily target PBP2, induced expression of the least. Second, we found that a single RS element was capable of inducing expression as efficiently as with the wild-type seven RS elements. Third, we found that the RS-element-mediated modulation of expression was strain dependent, suggesting that specific host factors might be involved in the transcription. And finally, we observed that ClpP regulates its own expression, as the expression of was higher in a -deficient mutant. This suggests that ClpP is involved in the degradation of activator(s) involved in its own transcription.
是人类口腔中的主要细菌之一,与龋齿有关。该细菌的致病性归因于其快速响应和适应口腔不断变化的条件的能力。这种适应性反应的主要参与者是 ClpP,它是一种细胞内蛋白酶,参与应激反应中错误折叠蛋白的降解。 编码一个单一基因,其上游区域独特地包含多个串联重复序列 (RS)。在这里,我们研究了 在各种应激下的表达,并报告了一些新的发现。首先,我们发现,在亚抑菌浓度下,某些细胞壁损伤抗生素能够诱导 的表达。具体来说,靶向青霉素结合蛋白 3 (PBP3) 的第三代和第四代头孢菌素强烈增强了 的表达。然而,当使用与 PBP3 亲和力较低的第一代头孢菌素时,诱导 的表达较弱。令人惊讶的是,主要靶向 PBP2 的碳青霉烯类抗生素诱导 的表达最少。其次,我们发现单个 RS 元件能够像野生型七个 RS 元件一样有效地诱导 的表达。第三,我们发现 RS 元件介导的 表达的调节与菌株有关,这表明特定的宿主因素可能参与转录。最后,我们观察到 ClpP 调节自身的表达,因为在 ClpP 缺陷突变体中, 的表达更高。这表明 ClpP 参与了自身转录的激活剂 (s) 的降解。