The only enzyme responsible for cadaverine production in the major multidrug-resistant human pathogen Pseudomonas aeruginosa is the lysine decarboxylase LdcA. This enzyme modulates the general polyamine homeostasis, promotes growth, and reduces bacterial persistence during carbenicillin treatment. Here we present a 3.7-Å resolution cryoelectron microscopy structure of LdcA. We introduce an original approach correlating phylogenetic signal with structural information and reveal possible recombination among LdcA and arginine decarboxylase subfamilies within structural domain boundaries. We show that LdcA is involved in full virulence in an insect pathogenesis model. Furthermore, unlike its enterobacterial counterparts, LdcA is regulated neither by the stringent response alarmone ppGpp nor by the AAA+ ATPase RavA. Instead, the P. aeruginosa ravA gene seems to play a defensive role. Altogether, our study identifies LdcA as an important player in P. aeruginosa physiology and virulence and as a potential drug target.

中文翻译：

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铜绿假单胞菌赖氨酸脱羧酶LdcA的结构，功能和进化。

在主要的多药耐药性人类病原体铜绿假单胞菌中，尸体产生的唯一酶是赖氨酸脱羧酶LdcA。在羧苄青霉素治疗期间，该酶调节一般的多胺稳态，促进生长，并减少细菌的持久性。在这里，我们介绍了LdcA的3.7Å分辨率的冷冻电子显微镜结构。我们介绍了一种将系统发生信号与结构信息相关的原始方法，并揭示了结构域边界内LdcA和精氨酸脱羧酶亚家族之间可能的重组。我们显示LdcA参与昆虫致病模型中的完全毒力。此外，与其肠杆菌类似物不同，LdcA既不受严格应答警报蛋白ppGpp的调节，也不受AAA + ATPase RavA的调节。相反，P。铜绿假单胞菌ravA基因似乎起了防御作用。总而言之，我们的研究确定LdcA是铜绿假单胞菌生理和毒力的重要参与者，并且是潜在的药物靶标。