ADP-ribosyltransferases (ARTs) are a widespread superfamily of enzymes frequently employed in pathogenic strategies of bacteria. Legionella pneumophila, the causative agent of Legionnaires disease, has acquired over 330 translocated effectors that showcase remarkable biochemical and structural diversity. Here we took a bioinformatic approach to search the Legionella effector repertoire for additional divergent members of the ART superfamily and identified an ART domain in Lpg0181. We show that L. pneumophila Lpg0181 targets a specific class of 120-kDa NAD+-dependent glutamate dehydrogenase (GDH) enzymes found in fungi and protists, including many natural hosts of Legionella. Lpg0181 targets a conserved arginine residue in the NAD+ -binding pocket of GDH, thereby blocking oxidative deamination of glutamate. While intracellular pathogens employ diverse virulence mechanisms to overcome host-limited nutrient availability, Lpg0181 is to the best of our knowledge the first example of a Legionella effector which directly targets a host metabolic enzyme.

中文翻译：

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军团菌效应物ADP-核糖基转移酶可灭活谷氨酸脱氢酶

ADP-核糖基转移酶（ARTs）是广泛用于细菌致病策略的酶超家族。退伍军人病菌是军团病的病原体，已经获得了330多个易位效应子，它们具有显着的生化和结构多样性。在这里，我们采取了一种生物信息学方法来搜寻军团菌效应子库，以寻找ART超家族的其他不同成员，并在Lpg0181中鉴定出ART域。我们显示，嗜肺乳杆菌Lpg0181靶向在真菌和原生生物（包括军团菌的许多天然宿主）中发现的一类特定的120 kDa NAD +依赖性谷氨酸脱氢酶（GDH）酶。Lpg0181靶向GDH的NAD +结合口袋中的保守精氨酸残基，从而阻止了谷氨酸的氧化脱氨。