MomL, a novel marine-derived N-acyl homoserine lactonase from Muricauda olearia.
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 × 10(5) 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.
College of Marine Life Sciences, Ocean University of China, Qingdao, China.
Kaihao
K
Tang
College of Marine Life Sciences, Ocean University of China, Qingdao, China.
Ying
Y
Su
Laboratory of Pharmaceutical Microbiology, Ghent University, Ghent, Belgium.
Gilles
G
Brackman
College of Marine Life Sciences, Ocean University of China, Qingdao, China.
Fangyuan
F
Cui
College of Marine Life Sciences, Ocean University of China, Qingdao, China.
Yunhui
Y
Zhang
College of Marine Life Sciences, Ocean University of China, Qingdao, China.
Xiaochong
X
Shi
Laboratory of Pharmaceutical Microbiology, Ghent University, Ghent, Belgium.
Tom
T
Coenye
College of Marine Life Sciences, Ocean University of China, Qingdao, China xhzhang@ouc.edu.cn.
Xiao-Hua
XH
Zhang
D000818:Animals; D054742:Acyl-Butyrolactones / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000382:microbiology; D002265:Carboxylic Ester Hydrolases / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism; D020134:Catalytic Domain; D002853:Chromatography, Liquid; D004195:Disease Models, Animal; D004252:DNA Mutational Analysis; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D041965:Flavobacteriaceae / Q000201:enzymology / Q000235:genetics; D007700:Kinetics; D013058:Mass Spectrometry; D008670:Metals / Q000378:metabolism; D008969:Molecular Sequence Data; D011485:Protein Binding; D021382:Protein Sorting Signals; D011550:Pseudomonas aeruginosa / Q000472:pathogenicity / Q000502:physiology; D053038:Quorum Sensing; D017422:Sequence Analysis, DNA; D014774:Virulence
D054742:Acyl-Butyrolactones; D002265:Carboxylic Ester Hydrolases; D004269:DNA, Bacterial; D008670:Metals; C432003:N-acyl homoserine lactonase; D021382:Protein Sorting Signals