Structure, Function, and Evolution of the Pseudomonas aeruginosa Lysine Decarboxylase LdcA

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. [Display omitted] •The structure of the P. aeruginosa LdcA is solved to 3.7-Å resolution by cryo-EM•The phylogenetic signal shifts within structural/functional domains of LAdcs•LdcA is involved in P. aeruginosa physiology and full virulence•P. aeruginosa ravAviaA operon has a potentially defensive function Kandiah et al. solve the structure of the lysine decarboxylase LdcA from a human pathogen Pseudomonas aeruginosa by cryo-EM. They use evolutionary information to analyze the system, demonstrate involvement of LdcA in full virulence of the pathogen in vivo, and propose to target this protein for therapeutic interventions.