Identification of a novel subfamily of bacterial AAT-fold basic amino acid decarboxylases and functional characterization of its first representative: Pseudomonas aeruginosa LdcA

Abstract

Polyamines are small amino-acid derived polycations capable of binding negatively charged macromolecules. Bacterial polyamines are structurally and functionally diverse, and are mainly produced biosynthetically by PLP-dependent amino acid decarboxylases referred to as LAOdcs (Lysine-Arginine-Ornithine decarboxylases). In a phylogenetically limited group of bacteria, LAOdcs are also induced in response to acid stress. Here, we performed an exhaustive phylogenetic analysis of the AAT-fold LAOdcs which showcased the ancestral nature of their short forms in Cyanobacteria and Firmicutes, and emergence of distinct subfamilies of long LAOdcs in Proteobacteria. We identified a novel subfamily of lysine decarboxylases, LdcA, ancestral in Betaproteobacteria and Pseudomortadaceae {Gammaproteobacteria). We analyzed the expression of LdcA from Pseudomonas aeruginosa, and uncovered its role, intimately linked to cadaverine production, in promoting growth and reducing persistence of this multidrug resistant human pathogen during carbenicillin treatment. Finally, we documented a certain redundancy in the function of the three main polyamines - cadaverine, putrescine and spermidine - in P. aeruginosa by demonstrating the link between their intracellular level, as well as the capacity of putrescine and spermidine to complement the growth phenotype of the IdcA mutant.