Pseudomonas aeruginosa is a widely found opportunistic pathogen. The emergence of multidrug-resistant strains and persistent chronic infections have increased. The protein encoded by the pa0423 gene in P. aeruginosa is proposed to be critical for pathogenesis and could be a virulence-promoting protease or a bacterial lipocalin that binds a lipid-like antibiotic for drug resistance. Although two functions of proteolysis and antibiotic resistance are mutually related to bacterial survival in the host, it is very unusual for a single-domain protein to target unrelated ligand molecules such as protein substrates and lipid-like antibiotics. To clearly address the biological role of the PA0423 protein, we performed structural and biochemical studies. We found that PA0423 adopts a single-domain β-barrel structure and belongs to the lipocalin family. The PA0423 structure houses an internal tubular cavity, which accommodates a ubiquinone-8 molecule. Furthermore, we reveal that PA0423 can directly interact with the polymyxin B antibiotic using the internal cavity, suggesting that PA0423 has a physiological function in the antibiotic resistance of P. aeruginosa.

铜绿假单胞菌是一种广泛发现的机会病原体。多重耐药菌株和持续性慢性感染的出现增加了。铜绿假单胞菌pa0423基因编码的蛋白质拟议中的“拟南芥”对发病机理至关重要，可能是一种促进毒性的蛋白酶或结合脂质样抗生素产生耐药性的细菌脂钙蛋白。尽管蛋白水解和抗生素抗性的两个功能与宿主中细菌的存活相互关联，但单结构域蛋白质靶向不相关的配体分子（例如蛋白质底物和类脂质抗生素）是非常不寻常的。为了清楚地说明PA0423蛋白的生物学作用，我们进行了结构和生化研究。我们发现PA0423采用单域β桶结构，属于lipocalin家族。PA0423结构容纳一个内部管状空腔，该空腔容纳一个泛醌8分子。此外，我们发现PA0423可以利用内腔直接与多粘菌素B抗生素相互作用，铜绿假单胞菌。