MomL, a Novel Marine-Derived N-Acyl Homoserine Lactonase from Muricauda olearia
MomL, a Novel Marine-Derived N-Acyl Homoserine Lactonase from Muricauda olearia
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MomL，一种来自 Muricauda olearia 的新型海洋衍生 N-酰基高丝氨酸内酯酶
DOI：
10.1128/aem.02805-14
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发表时间：
2015-01-01
影响因子：
4.4
通讯作者：
Zhang, Xiao-Hua
中科院分区：
文献类型：
--
作者：
Tang, Kaihao;Su, Ying;Zhang, Xiao-Hua
摘要 革兰氏阴性细菌利用 N-酰基高丝氨酸内酯 (AHL) 作为群体感应 (QS) 信号分子进行种间通讯，而 AHL 依赖性 QS 与许多细菌病原体的毒力因子产生有关。群体猝灭，即信号分子的酶促降解，会减弱毒力而不是杀死病原体，从而降低耐药性进化的可能性。在之前的研究中，我们发现Muricauda olearia Th120属于黄杆菌纲，具有很强的AHL降解活性。在这项研究中，从 Th120 中鉴定出一种 AHL 内酯酶（命名为 MomL），它可以降解短链和长链 AHL，无论 C-3 位是否有氧代基团取代。液相色谱-质谱分析表明，MomL 作为 AHL 内酯酶发挥作用，通过内酯水解催化 AHL 降解。 MomL 是一种 AHL 内酯酶，属于金属-β-内酰胺酶超家族，具有 N 末端信号肽。 MomL 对 C6-HSL 的总体催化效率为 ∼2.9 × 105 s−1 M−1。金属分析和定点突变表明，与 AiiA 相比，MomL 具有不同的金属结合能力，需要组氨酸和天冬氨酸残基才能发挥活性，同时它与属于金属-β-内酰胺酶超家族的其他 AHL 内酯酶共享“HXHXDH”基序。这表明MomL是新型分泌型AHL内酯酶的代表。此外，MomL 显着减弱了秀丽隐杆线虫感染模型中铜绿假单胞菌的毒力，这表明 MomL 有潜力用作治疗剂。
ABSTRACT Gram-negative bacteria use N-acyl homoserine lactones (AHLs) as quorum sensing (QS) signaling molecules for interspecies communication, and AHL-dependent QS is related with virulence factor production in many bacterial pathogens. Quorum quenching, the enzymatic degradation of the signaling molecule, would attenuate virulence rather than kill the pathogens, and thereby reduce the potential for evolution of drug resistance. In a previous study, we showed that Muricauda olearia Th120, belonging to the class Flavobacteriia, has strong AHL degradative activity. In this study, an AHL lactonase (designated MomL), which could degrade both short- and long-chain AHLs with or without a substitution of oxo-group at the C-3 position, was identified from Th120. Liquid chromatography-mass spectrometry analysis demonstrated that MomL functions as an AHL lactonase catalyzing AHL degradation through lactone hydrolysis. MomL is an AHL lactonase belonging to the metallo-β-lactamase superfamily that harbors an N-terminal signal peptide. The overall catalytic efficiency of MomL for C6-HSL is ∼2.9 × 105 s−1 M−1. Metal analysis and site-directed mutagenesis showed that, compared to AiiA, MomL has a different metal-binding capability and requires the histidine and aspartic acid residues for activity, while it shares the “HXHXDH” motif with other AHL lactonases belonging to the metallo-β-lactamase superfamily. This suggests that MomL is a representative of a novel type of secretory AHL lactonase. Furthermore, MomL significantly attenuated the virulence of Pseudomonas aeruginosa in a Caenorhabditis elegans infection model, which suggests that MomL has the potential to be used as a therapeutic agent.