幽門螺桿菌存在于胃部及十二指腸的各個區(qū)域內(nèi),。它會引起胃黏膜輕微的慢性發(fā)炎,，甚至導(dǎo)致胃及十二指腸潰瘍及胃癌。根據(jù)澳大利亞科學(xué)家日前在《微生物學(xué)》雜志上發(fā)表的一篇新論文,，依賴維生素B6的鞭毛糖基化是幽門螺桿菌充分運動和具有毒性所必需的,。
在生物體外,，延長幽門螺桿菌的培育導(dǎo)致了傳染性的喪失，以及在小鼠中造成了細(xì)菌負(fù)荷的減少,，并且在低傳染性隔離中被顯著下調(diào)的基因被發(fā)現(xiàn)使用了整體的基因表達(dá)譜,。于是墨爾本市莫納什大學(xué)的Alexandra Grubman與法國巴黎的同事一道聚焦了兩種基因，pdxJ和pdxA,，它們分別被視為PdxJ和PdxA的編碼同系物,，是與吡哆醛-5-磷酸（PLP）——維生素B6的活化態(tài)——的全程合成有關(guān)的兩種大腸桿菌蛋白質(zhì)。
研究人員發(fā)現(xiàn),，幽門螺桿菌pdxJ無法被分裂,，這意味著它可能是必不可少的。同基因型的幽門螺桿菌pdxA在形成突變后表現(xiàn)出了比親代菌株更慢的生長速度,。這種生長缺陷能夠被PLP的加入,，或是被pdxA的一個完整副本的引入所恢復(fù)。更進(jìn)一步的研究表明,，幽門螺桿菌pdxJ和pdxA能夠在大腸桿菌中交叉補足一種PLP缺陷，意味著它們編碼的蛋白質(zhì)與維生素B6的生物合成有關(guān),。此外,，小鼠感染研究顯示，幽門螺桿菌的集群現(xiàn)象在缺乏一種pdxA的功能拷貝的情況下會極大地減少,。
那么,，維生素B6在集群中的確切功能到底是什么？在幽門螺桿菌中,，維生素B6是PseC——鞭毛糖基化所需的一種轉(zhuǎn)氨酶——的一種輔因子,。對軟瓊脂板上的細(xì)菌活性進(jìn)行的分析，以及活體細(xì)胞成像試驗表明,，pdxA突變是非能動的,，并且電子顯微鏡顯示，它們?nèi)狈Ρ廾?。對整個細(xì)胞溶解產(chǎn)物,，以及野生型和pdxA突變幽門螺桿菌的剪切鞭毛樣本進(jìn)行的分析顯示，pdxA突變能夠產(chǎn)生鞭毛蛋白A,，但它并不能被輸送到細(xì)胞表面,，且不能被糖基化。
這是與維生素B6生物合成有關(guān)的酶首次作為一種細(xì)菌毒性因子被確定下來,，同時研究人員推斷,，對維生素B6合成路徑的破壞將帶來新的療法。（生物谷Bioon.com）
生物谷推薦原文出處：
mBio™ doi:10.1128/mBio.00112-10.
Vitamin B6 Is Required for Full Motility and Virulence in Helicobacter pylori
Alexandra Grubman a*, Alexandra Phillips a , Marie Thibonnier b*, Maria Kaparakis-Liaskos a*, Chad Johnson c , Jean-Michel Thiberge d*, Fiona J. Radcliff e , Chantal Ecobichon d*, Agnès Labigne d , Hilde de Reuse b , George L. Mendz f , and Richard L. Ferrero a,d*
ABSTRACT
Despite recent advances in our understanding of how Helicobacter pylori causes disease, the factors that allow this pathogen to persist in the stomach have not yet been fully characterized. To identify new virulence factors in H. pylori, we generated low-infectivity variants of a mouse-colonizing H. pylori strain using the classical technique of in vitro attenuation. The resulting variants and their highly infectious progenitor bacteria were then analyzed by global gene expression profiling. The gene expression levels of five open reading frames (ORFs) were significantly reduced in low-infectivity variants, with the most significant changes observed for ORFs HP1583 and HP1582. These ORFs were annotated as encoding homologs of the Escherichia coli vitamin B6 biosynthesis enzymes PdxA and PdxJ. Functional complementation studies with E. coli confirmed H. pylori PdxA and PdxJ to be bona fide homologs of vitamin B6 biosynthesis enzymes. Importantly, H. pylori PdxA was required for optimal growth in vitro and was shown to be essential for chronic colonization in mice. In addition to having a well-known metabolic role, vitamin B6 is necessary for the synthesis of glycosylated flagella and for flagellum-based motility in H. pylori. Thus, for the first time, we identify vitamin B6 biosynthesis enzymes as novel virulence factors in bacteria. Interestingly, pdxA and pdxJ orthologs are present in a number of human pathogens, but not in mammalian cells. We therefore propose that PdxA/J enzymes may represent ideal candidates for therapeutic targets against bacterial pathogens.
IMPORTANCE Approximately half of the world’s population is infected with H. pylori, yet how H. pylori bacteria establish chronic infections in human hosts remains elusive. From gene array studies, we identified two genes as representing potentially novel colonization factors for H. pylori. These genes encoded enzymes involved in the synthesis of vitamin B6, an important molecule for many metabolic reactions in living organisms. Little is currently known regarding vitamin B6 biosynthesis in human pathogens. We showed that mutant H. pylori bacteria lacking an enzyme involved in de novo vitamin B6 biosynthesis, PdxA, were unable to synthesize motility appendages (flagella) and were unable to establish chronic colonization in mice. Thus, this work identifies vitamin B6 biosynthesis enzymes as novel virulence factors for bacterial pathogens. Interestingly, a number of human pathogens, but not their mammalian hosts, possess these genes, which suggests that Pdx enzymes may represent ideal candidates for new therapeutic targets.
