A Porphyromonas gingivalis tyrosine phosphatase is a multifunctional regulator of virulence attributes
A Porphyromonas gingivalis tyrosine phosphatase is a multifunctional regulator of virulence attributes
复制标题
DOI：
10.1111/j.1365-2958.2008.06338.x
复制
发表时间：
2008-09-01
影响因子：
3.6
通讯作者：
Lamont, Richard J.
中科院分区：
文献类型：
--
作者：
Maeda, Kazuhiko;Tribble, Gena D.;Lamont, Richard J.
低分子量酪氨酸磷酸酶（LMWTP）广泛存在于原核生物中;然而，对这些酶控制的信号级联的理解仍在出现。牙龈卟啉单胞菌是一种机会性口腔病原体，表达LMWTP，Ltp 1，在生物膜群落中受到差异调节。在这里，我们的特点LTP 1的酶活性，并通过使用缺乏LTP 1或表达催化缺陷LTP 1的突变体，表明酪氨酸磷酸酶活性限制了单种生物膜的发展和社区发展的先行口腔生物膜成分戈登链球菌。胞外多糖的产生是下调Ltp 1通过转录调控参与生物合成和运输的多个基因。此外，Ltp 1调节luxS的转录活性，从而影响生物膜群落中的AI-2依赖性信号传导。在没有Ltp 1转录的情况下，hmu血红素摄取位点减少，因此在Ltp 1突变体中血红素的摄取受损。牙龈菌蛋白酶Kgp和RgpA/B在Ltp 1突变体中保持磷酸化。磷酸化Rgp分泌不良，而磷酸化Kgp的细胞表面活性增强。Ltp 1通过控制几种毒力相关特性的活性，可以抑制牙龈卟啉单胞菌的致病潜力，并维持与宿主的生物相互作用。
Low Molecular Weight Tyrosine Phosphatases (LMWTP) are widespread in prokaryotes; however, understanding of the signalling cascades controlled by these enzymes is still emerging. Porphyromonas gingivalis, an opportunistic oral pathogen, expresses a LMWTP, Ltp1, that is differentially regulated in biofilm communities. Here we characterize the enzymatic activity of Ltp1 and, through the use of mutants that lack Ltp1 or expresses catalytically defective Ltp1, show that tyrosine phosphatase activity constrains both monospecies biofilm development and community development with the antecedent oral biofilm constituent Streptococcus gordonii. Exopolysaccharide production is downregulated by Ltp1 through transcriptional regulation of multiple genes involved in biosynthesis and transport. Furthermore, Ltp1 regulates transcriptional activity of luxS and thus impacts AI-2-dependent signalling in biofilm communities. In the absence of Ltp1 transcription across the hmu haemin uptake locus is reduced, and consequently uptake of haemin is impaired in the Ltp1 mutant. The gingipain proteinases Kgp and RgpA/B remain phosphorylated in the Ltp1 mutant. Phosphorylated Rgps are poorly secreted, whereas cell surface activity of phosphorylated Kgp is enhanced. By controlling the activity of several virulence-associated properties, Ltp1 may restrain the pathogenic potential of P. gingivalis and maintain a commensal interaction with the host.