Lactonase Specificity Is Key to Quorum Quenching in Pseudomonas aeruginosa

Rémy, Benjamin; Plener, Laure; Decloquement, Philippe; Armstrong, Nicholas; Elias, Mikael; Daudé, David; Chabrière, Éric

doi:10.3389/fmicb.2020.00762

Cited by 43 publications

(43 citation statements)

References 81 publications

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“…In this study, we used two well-characterized lactonases with distinct substrate specificity. One of the enzymes, GcL, hydrolyzes both C4-and 3-oxo-C12 HSL (Bergonzi et al, 2019), whereas the other lactonase, SsoPox W263I, prefers 3-oxo-C12 HSL (Hiblot et al, 2013;Rémy et al, 2019; see Supplementary Table S2). Therefore, GcL is expected to quench both AHL-based QS circuits in P. aeruginosa, and SsoPox W263I will mainly quench the 3-oxo-C12 HSL based QS circuit.…”

Section: Both Lactonases Degrade Acyl Homoserine Lactones In Culturesmentioning

confidence: 99%

Effects of Signal Disruption Depends on the Substrate Preference of the Lactonase

et al. 2020

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Many bacteria produce and use extracellular signaling molecules such as acyl homoserine lactones (AHLs) to communicate and coordinate behavior in a cell-density dependent manner, via a communication system called quorum sensing (QS). This system regulates behaviors including but not limited to virulence and biofilm formation. We focused on Pseudomonas aeruginosa, a human opportunistic pathogen that is involved in acute and chronic lung infections and which disproportionately affects people with cystic fibrosis. P. aeruginosa infections are becoming increasingly challenging to treat with the spread of antibiotic resistance. Therefore, QS disruption approaches, known as quorum quenching, are appealing due to their potential to control the virulence of resistant strains. Interestingly, P. aeruginosa is known to simultaneously utilize two main QS circuits, one based on C4-AHL, the other with 3-oxo-C12-AHL. Here, we evaluated the effects of signal disruption on 39 cystic fibrosis clinical isolates of P. aeruginosa, including drug resistant strains. We used two enzymes capable of degrading AHLs, known as lactonases, with distinct substrate preference: one degrading 3-oxo-C12-AHL, the other degrading both C4-AHL and 3-oxo-C12-AHL. Two lactonases were used to determine the effects of signal disruption on the clinical isolates, and to evaluate the importance of the QS circuits by measuring effects on virulence factors (elastase, protease, and pyocyanin) and biofilm formation. Signal disruption results in at least one of these factors being inhibited for most isolates (92%). Virulence factor activity or production were inhibited by up to 100% and biofilm was inhibited by an average of 2.3 fold. Remarkably, the treatments led to distinct inhibition profiles of the isolates; the treatment with the lactonase degrading both signaling molecules resulted in a higher fraction of inhibited isolates (77% vs. 67%), and the simultaneous inhibition of more virulence factors per strain (2 vs. 1.5). This finding suggests that the lactonase AHL preference is key to its inhibitory spectrum and is an essential parameter to improve quorum quenching strategies.

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Section: Both Lactonases Degrade Acyl Homoserine Lactones In Culturesmentioning

confidence: 99%

Effects of Signal Disruption Depends on the Substrate Preference of the Lactonase

et al. 2020

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“…A new degradation pathway for AHL in strain W-7 is proposed as follows: AHL is initially degraded into N-hexanoyl-l-homoserine; then, N-hexanoyl-l-homoserine is converted into hexanamide and propanamide, and finally, propanamide is degraded into carbon dioxide and water. Quorum quenching is regarded as a novel promising method for preventing and controlling bacterial diseases based on QS microorganisms, an alternative to antibiotics, to reduce the risk of drug resistance (Abed et al, 2013;Schuster et al, 2013;Rémy et al, 2020). There are various approaches to interfering with the QS system by QQ such as inhibiting signal synthesis, hindering the modification of signals, and inactivating QQ signals via enzymes or bacterial degradation (Bhatt et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

“…Quorum quenching is regarded as a novel promising method for preventing and controlling bacterial diseases based on QS microorganisms, an alternative to antibiotics, to reduce the risk of drug resistance ( Abed et al, 2013 ; Schuster et al, 2013 ; Rémy et al, 2020 ). There are various approaches to interfering with the QS system by QQ such as inhibiting signal synthesis, hindering the modification of signals, and inactivating QQ signals via enzymes or bacterial degradation ( Bhatt et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Exploration of the Quorum-Quenching Mechanism in Pseudomonas nitroreducens W-7 and Its Potential to Attenuate the Virulence of Dickeya zeae EC1

Zhang

Fan

et al. 2021

Front. Microbiol.

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Quorum quenching (QQ) is a novel, promising strategy that opens up a new perspective for controlling quorum-sensing (QS)-mediated bacterial pathogens. QQ is performed by interfering with population-sensing systems, such as by the inhibition of signal synthesis, catalysis of degrading enzymes, and modification of signals. In many Gram-negative pathogenic bacteria, a class of chemically conserved signaling molecules named N-acyl homoserine lactones (AHLs) have been widely studied. AHLs are involved in the modulation of virulence factors in various bacterial pathogens including Dickeya zeae. Dickeya zeae is the causal agent of plant-rot disease of bananas, rice, maize, potatoes, etc., causing enormous economic losses of crops. In this study, a highly efficient AHL-degrading bacterial strain W-7 was isolated from activated-sludge samples and identified as Pseudomonas nitroreducens. Strain W-7 revealed a superior ability to degrade N-(3-oxododecanoyl)-l-homoserine lactone (OdDHL) and completely degraded 0.2 mmol/L of OdDHL within 48 h. Gas chromatography-mass spectrometry (GC-MS) identified N-cyclohexyl-propanamide as the main intermediate metabolite during AHL biodegradation. A metabolic pathway for AHL in strain W-7 was proposed based on the chemical structure of AHL and intermediate products. In addition to the degradation of OdDHL, this strain was also found to be capable of degrading a wide range of AHLs including N-(3-oxohexanoyl)-l-homoserine lactone (OHHL), N-(3-oxooctanoyl)-l-homoserine lactone (OOHL), and N-hexanoyl-l-homoserine lactone (HHL). Moreover, the application of strain W-7 as a biocontrol agent could substantially attenuate the soft rot caused by D. zeae EC1 to suppress tissue maceration in various host plants. Similarly, the application of crude enzymes of strain W-7 significantly reduced the disease incidence and severity in host plants. These original findings unveil the biochemical aspects of a highly efficient AHL-degrading bacterial isolate and provide useful agents that exhibit great potential for the control of infectious diseases caused by AHL-dependent bacterial pathogens.

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“…A broad‐spectrum lactonase preparation based on Sso Pox lactonase from the archaeon Saccharolobus solfataricus was obtained from Gene&GreenTK (Marseille, France), which is specialized in the development of enzymes, including quorum quenching lactonases. The commercial preparation obtained from Gene&GreenTK was produced heterogeneously in E. coli , purified to homogeneity by size‐exclusion chromatography (Hiblot et al ., 2013; Guendouze et al ., 2017; Rémy et al ., 2020) and eluted in HEPES buffer (50 mM HEPES, 150 mM NaCl and pH 8.0).…”

Section: Methodsmentioning

confidence: 99%

Quorum sensing disruption regulates hydrolytic enzyme and biofilm production in estuarine bacteria

Urvoy

Lami

Dréanno

et al. 2021

Environmental Microbiology

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Summary Biofilms of heterotrophic bacteria cover organic matter aggregates and constitute hotspots of mineralization, primarily acting through extracellular hydrolytic enzyme production. Nevertheless, regulation of both biofilm and hydrolytic enzyme synthesis remains poorly investigated, especially in estuarine ecosystems. In this study, various bioassays, mass spectrometry and genomics approaches were combined to test the possible involvement of quorum sensing (QS) in these mechanisms. QS is a bacterial cell–cell communication system that relies notably on the emission of N‐acylhomoserine lactones (AHLs). In our estuarine bacterial collection, we found that 28 strains (9%), mainly Vibrio, Pseudomonas and Acinetobacter isolates, produced at least 14 different types of AHLs encoded by various luxI genes. We then inhibited the AHL QS circuits of those 28 strains using a broad‐spectrum lactonase preparation and tested whether biofilm production as well as β‐glucosidase and leucine‐aminopeptidase activities were impacted. Interestingly, we recorded contrasted responses, as biofilm production, dissolved and cell‐bound β‐glucosidase and leucine‐aminopeptidase activities significantly increased in 4%–68% of strains but decreased in 0%–21% of strains. These findings highlight the key role of AHL‐based QS in estuarine bacterial physiology and ultimately on biogeochemical cycles. They also point out the complexity of QS regulations within natural microbial assemblages.

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Lactonase Specificity Is Key to Quorum Quenching in Pseudomonas aeruginosa

Cited by 43 publications

References 81 publications

Effects of Signal Disruption Depends on the Substrate Preference of the Lactonase

Effects of Signal Disruption Depends on the Substrate Preference of the Lactonase

Exploration of the Quorum-Quenching Mechanism in Pseudomonas nitroreducens W-7 and Its Potential to Attenuate the Virulence of Dickeya zeae EC1

Quorum sensing disruption regulates hydrolytic enzyme and biofilm production in estuarine bacteria

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