Dou Y, Robles A, Roy F, Aruni A W, Sandberg L, Nothnagel E, Fletcher H M
Division of Microbiology and Molecular Genetics, School of Medicine, Loma Linda University, Loma Linda, CA, USA.
Botany and Plant Sciences, University of California, Riverside, CA, USA.
Mol Oral Microbiol. 2015 Oct;30(5):347-60. doi: 10.1111/omi.12098. Epub 2015 May 8.
Previous studies have shown that VimA, an acetyltransferase, can modulate gingipain biogenesis in Porphyromonas gingivalis. Inactivation of the vimA gene resulted in isogenic mutants that showed a late onset of gingipain activity that only occurred during the stationary growth phase. To further elucidate the role and contribution of the gingipains in this VimA-dependent process, isogenic mutants defective in the gingipain genes in the vimA-deficient genetic background were evaluated. In contrast with the wild-type strain, RgpB and Kgp gingipain activities were absent in exponential phase in the ∆rgpA::tetQ-vimA::ermF mutant. However, these activities increased to 31 and 53%, respectively, of that of the wild-type during stationary phase. In the ∆rgpA::cat-∆kgp::tetQ-vimA::ermF mutant, the RgpB protein was observed in the extracellular fraction but no activity was present even at the stationary growth phase. There was no gingipain activity observed in the ∆rgpB::cat-∆kgp::tetQ-vimA::ermF mutant whereas Kgp activity in ∆rgpA::cat-∆rgpB::tetQ-vimA::ermF mutant was 24% of the wild-type at late stationary phase. In contrast to RgpA, the glycosylation profile of the RgpB catalytic domain from both W83 and P. gingivalis FLL92 (vimA::ermF) showed similarity. Taken together, the results suggest multiple gingipain activation pathways in P. gingivalis. Whereas the maturation pathways for RgpA and RgpB are different, the late-onset gingipain activity in the vimA-defective mutant was due to activation/maturation of RgpB and Kgp. Moreover, unlike RgpA, which is VimA-dependent, the maturation/activation pathways for RgpB and Kgp are interdependent in the absence VimA.
先前的研究表明,乙酰转移酶VimA可调节牙龈卟啉单胞菌中牙龈蛋白酶的生物合成。vimA基因的失活导致同基因突变体,这些突变体显示牙龈蛋白酶活性出现较晚,仅在稳定生长期才会出现。为了进一步阐明牙龈蛋白酶在这个VimA依赖过程中的作用和贡献,对vimA缺陷遗传背景下牙龈蛋白酶基因有缺陷的同基因突变体进行了评估。与野生型菌株相比,在∆rgpA::tetQ-vimA::ermF突变体的指数生长期不存在RgpB和Kgp牙龈蛋白酶活性。然而,在稳定期,这些活性分别增加到野生型的31%和53%。在∆rgpA::cat-∆kgp::tetQ-vimA::ermF突变体中,在细胞外部分观察到了RgpB蛋白,但即使在稳定生长期也没有活性。在∆rgpB::cat-∆kgp::tetQ-vimA::ermF突变体中未观察到牙龈蛋白酶活性,而在∆rgpA::cat-∆rgpB::tetQ-vimA::ermF突变体中,Kgp活性在稳定期末期为野生型的24%。与RgpA不同,来自W83和牙龈卟啉单胞菌FLL92(vimA::ermF)的RgpB催化结构域的糖基化谱显示出相似性。综上所述,结果表明牙龈卟啉单胞菌中存在多种牙龈蛋白酶激活途径。虽然RgpA和RgpB的成熟途径不同,但vimA缺陷突变体中牙龈蛋白酶活性出现较晚是由于RgpB和Kgp的激活/成熟。此外,与依赖VimA的RgpA不同,在没有VimA的情况下,RgpB和Kgp的成熟/激活途径是相互依赖的。