VimA-Dependent Modulation of Acetyl Coenzyme A Levels and Lipid A Biosynthesis Can Alter Virulence in Porphyromonas gingivalis
VimA-Dependent Modulation of Acetyl Coenzyme A Levels and Lipid A Biosynthesis Can Alter Virulence in Porphyromonas gingivalis
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DOI：
10.1128/iai.06062-11
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发表时间：
2012-02-01
影响因子：
3.1
通讯作者：
Fletcher, H. M.
中科院分区：
文献类型：
--
作者：
Aruni, A. Wilson;Lee, J.;Fletcher, H. M.
牙龈卟啉单胞菌VimA蛋白具有多功能，可以调节其几个主要的毒力因子。为了进一步鉴定VIMA，我们对携带额外VIMA基因的牙龈假单胞菌FLL406和不同遗传背景的VIMA缺陷突变体进行了评估。33277菌株遗传背景中的VIMA缺陷突变体(FLL451)与W83遗传背景中的VIMA缺陷突变体(FLL92)具有相似的表型。与野生型相比，VIMA嵌合菌株牙龈假单胞菌FLL406的牙龈痛活性增加。牙龈假单胞菌FLL451的生物被膜能力是亲本菌株的5倍。与牙龈假单胞菌FLL451和FLL406孵育的HeLa细胞相比，FLL92对HeLa细胞的侵袭力降低，分别增加30%和40%。VIMA介导辅酶A(CoA)向异亮氨酸转移，降低支链氨基酸代谢。在VIMA缺陷突变体中，脂质A含量和相关蛋白发生了变化。VIMA嵌合体与几种蛋白质相互作用，这些蛋白质被发现具有IXXTG基序，类似于革兰氏阳性生物的分选基序。所有的蛋白质都有一个N末端的信号序列，推测其分选信号为L(P/T/S)x(T/N/D)G和两个独特的特征：EXGXTX和HISXXGXG，此外还有一个极尾。综上所述，这些观察进一步证实了VimA在调节毒力方面的多功能作用，可能是通过参与乙酰辅酶A转移和脂类A的合成，可能是通过蛋白质分类。
The Porphyromonas gingivalis VimA protein has multifunctional properties that can modulate several of its major virulence factors. To further characterize VimA, P. gingivalis FLL406 carrying an additional vimA gene and a vimA-defective mutant in a different P. gingivalis genetic background were evaluated. The vimA-defective mutant (FLL451) in the P. gingivalis ATCC 33277 genetic background showed a phenotype similar to that of the vimA-defective mutant (FLL92) in the P. gingivalis W83 genetic background. In contrast to the wild type, gingipain activity was increased in P. gingivalis FLL406, a vimA chimeric strain. P. gingivalis FLL451 had a five times higher biofilm-forming capacity than the parent strain. HeLa cells incubated with P. gingivalis FLL92 showed a decrease in invasion, in contrast to P. gingivalis FLL451 and FLL406, which showed increases of 30 and 40%, respectively. VimA mediated coenzyme A (CoA) transfer to isoleucine and reduced branched-chain amino acid metabolism. The lipid A content and associated proteins were altered in the vimA-defective mutants. The VimA chimera interacted with several proteins which were found to have an IXXTG motif, similar to the sorting motif of Gram-positive organisms. All the proteins had an N-terminal signal sequence with a putative sorting signal of L (P/T/S)x(T/N/D)G and two unique signatures of EXGXTX and HISXXGXG, in addition to a polar tail. Taken together, these observations further confirm the multifunctional role of VimA in modulating virulence possibly through its involvement in acetyl-CoA transfer and lipid A synthesis and possibly by protein sorting.