Pustelny Christian, Albers Alexander, Büldt-Karentzopoulos Klaudia, Parschat Katja, Chhabra Siri Ram, Cámara Miguel, Williams Paul, Fetzner Susanne
School of Molecular Medical Sciences, Centre for Biomolecular Sciences, University of Nottingham, Nottingham NG7 2RD, UK.
Chem Biol. 2009 Dec 24;16(12):1259-67. doi: 10.1016/j.chembiol.2009.11.013.
2-Heptyl-3-hydroxy-4(1H)-quinolone (PQS) is a quorum-sensing signal molecule used by Pseudomonas aeruginosa. The structural similarity between 3-hydroxy-2-methyl-4(1H)-quinolone, the natural substrate for the 2,4-dioxygenase, Hod, and PQS prompted us to investigate whether Hod quenched PQS signaling. Hod is capable of catalyzing the conversion of PQS to N-octanoylanthranilic acid and carbon monoxide. In P. aeruginosa PAO1 cultures, exogenously supplied Hod protein reduced expression of the PQS biosynthetic gene pqsA, expression of the PQS-regulated virulence determinants lectin A, pyocyanin, and rhamnolipids, and virulence in planta. However, the proteolytic cleavage of Hod by extracellular proteases, competitive inhibition by the PQS precursor 2-heptyl-4(1H)-quinolone, and PQS binding to rhamnolipids reduced the efficiency of Hod as a quorum-quenching agent. Nevertheless, these data indicate that enzyme-mediated PQS inactivation has potential as an antivirulence strategy against P. aeruginosa.
2-庚基-3-羟基-4（1H）-喹诺酮（PQS）是铜绿假单胞菌使用的一种群体感应信号分子。2,4-双加氧酶Hod的天然底物3-羟基-2-甲基-4（1H）-喹诺酮与PQS之间的结构相似性促使我们研究Hod是否会淬灭PQS信号。Hod能够催化PQS转化为N-辛酰邻氨基苯甲酸和一氧化碳。在铜绿假单胞菌PAO1培养物中，外源提供的Hod蛋白降低了PQS生物合成基因pqsA的表达、PQS调控的毒力决定因子凝集素A、绿脓菌素和鼠李糖脂的表达以及在植物中的毒力。然而，细胞外蛋白酶对Hod的蛋白水解切割、PQS前体2-庚基-4（1H）-喹诺酮的竞争性抑制以及PQS与鼠李糖脂的结合降低了Hod作为群体淬灭剂的效率。尽管如此，这些数据表明酶介导的PQS失活具有作为对抗铜绿假单胞菌的抗毒力策略的潜力。
