Reidl J, Schlör S, Kraiss A, Schmidt-Brauns J, Kemmer G, Soleva E
Zentrum für Infektionsforschung, Universität Würzburg, Röntgenring 11, 97070 Würzburg, Germany.
Mol Microbiol. 2000 Mar;35(6):1573-81. doi: 10.1046/j.1365-2958.2000.01829.x.
Exogenous NAD utilization or pyridine nucleotide cycle metabolism is used by many bacteria to maintain NAD turnover and to limit energy-dependent de novo NAD synthesis. The genus Haemophilus includes several important pathogenic bacterial species that require NAD as an essential growth factor. The molecular mechanisms of NAD uptake and processing are understood only in part for Haemophilus. In this report, we present data showing that the outer membrane lipoprotein e(P4), encoded by the hel gene, and an exported 5'-nucleotidase (HI0206), assigned as nadN, are necessary for NAD and NADP utilization. Lipoprotein e(P4) is characterized as an acid phosphatase that uses NADP as substrate. Its phosphatase activity is inhibited by compounds such as adenosine or NMN. The nadN gene product was characterized as an NAD-nucleotidase, responsible for the hydrolysis of NAD. H. influenzae hel and nadN mutants had defined growth deficiencies. For growth, the uptake and processing of the essential cofactors NADP and NAD required e(P4) and 5'-nucleotidase. In addition, adenosine was identified as a potent growth inhibitor of wild-type H. influenzae strains, when NADP was used as the sole source of nicotinamide-ribosyl.
许多细菌利用外源性烟酰胺腺嘌呤二核苷酸（NAD）的利用或吡啶核苷酸循环代谢来维持NAD周转，并限制能量依赖的NAD从头合成。嗜血杆菌属包括几种重要的致病细菌物种，它们需要NAD作为必需的生长因子。对于嗜血杆菌，NAD摄取和加工的分子机制仅部分为人所知。在本报告中，我们提供的数据表明，由hel基因编码的外膜脂蛋白e(P4)和被指定为nadN的一种分泌型5'-核苷酸酶（HI0206）对于NAD和NADP的利用是必需的。脂蛋白e(P4)被鉴定为一种以NADP为底物的酸性磷酸酶。其磷酸酶活性受到腺苷或烟酰胺单核苷酸（NMN）等化合物的抑制。nadN基因产物被鉴定为一种NAD核苷酸酶，负责NAD的水解。流感嗜血杆菌hel和nadN突变体具有明确的生长缺陷。为了生长，必需辅因子NADP和NAD的摄取和加工需要e(P4)和5'-核苷酸酶。此外，当NADP用作烟酰胺核糖基的唯一来源时，腺苷被鉴定为野生型流感嗜血杆菌菌株的一种强效生长抑制剂。
