Inhibitive Effect of Eugenol and Its Nanoemulsion on Quorum Sensing–Mediated Virulence Factors and Biofilm Formation by Pseudomonas aeruginosa

2019 ◽  
Vol 82 (3) ◽  
pp. 379-389 ◽  
Author(s):  
ZAIXIANG LOU ◽  
KEKGABILE S. LETSIDIDI ◽  
FUHAO YU ◽  
ZEJUN PEI ◽  
HONGXIN WANG ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Biofilm Formation ◽  
Homoserine Lactone ◽  
Expression Level ◽  
Signal Molecules ◽  
Acyl Homoserine Lactone ◽  
Swarming Motility ◽  
Violacein Production ◽  
Virulence Factor Production

ABSTRACT The aim of the present study was to evaluate the quorum sensing (QS) inhibition potential of eugenol and eugenol nanoemulsion against QS-dependent virulence factor production and gene expression, as well as biofilm formation in Pseudomonas aeruginosa. In the current study, eugenol nanoemulsion at a sub-MIC of 0.2 mg/mL specifically inhibited about 50% of the QS-mediated violacein production in Chromobacterium violaceum, as well as the production of N-(3-oxododecanoyl)-l-homoserine lactone (3-oxo-C12-HSL) and C4-HSL N-acyl homoserine lactone signal molecules, pyocyanin, and swarming motility in P. aeruginosa. The inhibitive effect of eugenol and its nanoemulsion on the expression of the QS synthase genes was concentration dependent, displaying 65 and 52% expression level for lasI, respectively, and 61 and 45% expression level for rhlI, respectively, at a concentration of 0.2 mg/mL. In addition, the inhibitive effect of eugenol and its nanoemulsion on the expression of the rhlA gene responsible for the production of rhamnolipid was also concentration dependent, displaying 65 and 51% expression level for the rhlA gene, respectively, at a concentration of 0.2 mg/mL. Eugenol and its nanoemulsion also displayed 36 and 63% respective inhibition of biofilm formation by P. aeruginosa at the 0.2 mg/mL concentration. Therefore, the nanoemulsion could be used as a novel QS-based antibacterial and antibiofilm agent for the control of harmful bacteria.

scholarly journals Mechanistic analysis of a synthetic inhibitor of the Pseudomonas aeruginosa LasI quorum-sensing signal synthase

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
O. Lidor ◽  
A. Al-Quntar ◽  
E. C. Pesci ◽  
D. Steinberg
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
In Silico ◽  
Biofilm Formation ◽  
Homoserine Lactone ◽  
Site Directed Mutagenesis ◽  
Great Promise ◽  
Acyl Homoserine Lactone ◽  
Virulence Determinants

Abstract Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen responsible for many human infections. LasI is an acyl-homoserine lactone synthase that produces a quorum-sensing (QS) signal that positively regulates numerous P. aeruginosa virulence determinants. The inhibition of the LasI protein is therefore an attractive drug target. In this study, a novel in silico to in vitro complementation was applied to screen thiazolidinedione-type compounds for their ability to inhibit biofilm formation at concentrations not affecting bacterial growth. The compound (z)-5-octylidenethiazolidine-2, 4-dione (TZD-C8) was a strong inhibitor of biofilm formation and chosen for further study. Structural exploration of in silico docking predicted that the compound had high affinity for the LasI activity pocket. The TZD-C8 compound was also predicted to create hydrogen bonds with residues Arg30 and Ile107. Site-directed mutagenesis (SDM) of these two sites demonstrated that TZD-C8 inhibition was abolished in the lasI double mutant PAO-R30D, I107S. In addition, in vitro swarming motility and quorum sensing signal production were affected by TZD-C 8, confirming this compound alters the cell to cell signalling circuitry. Overall, this novel inhibitor of P. aeruginosa quorum sensing shows great promise and validates our mechanistic approach to discovering inhibitors of LuxI-type acyl-homoserine lactone synthases.

scholarly journals Quorum Quenching by an N-Acyl-Homoserine Lactone Acylase from Pseudomonas aeruginosa PAO1

2006 ◽  
Vol 74 (3) ◽  
pp. 1673-1682 ◽  
Author(s):  
Charles F. Sio ◽  
Linda G. Otten ◽  
Robbert H. Cool ◽  
Stephen P. Diggle ◽  
Peter G. Braun ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Quorum Quenching ◽  
Homoserine Lactone ◽  
Side Chain ◽  
Signal Molecules ◽  
Acyl Homoserine Lactone ◽  
Beta Lactam ◽  
Signal Molecule ◽  
Pathogenic Potential

ABSTRACT The virulence of the opportunistic human pathogen Pseudomonas aeruginosa PAO1 is controlled by an N-acyl-homoserine lactone (AHL)-dependent quorum-sensing system. During functional analysis of putative acylase genes in the P. aeruginosa PAO1 genome, the PA2385 gene was found to encode an acylase that removes the fatty acid side chain from the homoserine lactone (HSL) nucleus of AHL-dependent quorum-sensing signal molecules. Analysis showed that the posttranslational processing of the acylase and the hydrolysis reaction type are similar to those of the beta-lactam acylases, strongly suggesting that the PA2385 protein is a member of the N-terminal nucleophile hydrolase superfamily. In a bioassay, the purified acylase was shown to degrade AHLs with side chains ranging in length from 11 to 14 carbons at physiologically relevant low concentrations. The substituent at the 3′ position of the side chain did not affect activity, indicating broad-range AHL quorum-quenching activity. Of the two main AHL signal molecules of P. aeruginosa PAO1, N-butanoyl-l-homoserine lactone (C4-HSL) and N-(3-oxododecanoyl)-l-homoserine lactone (3-oxo-C12-HSL), only 3-oxo-C12-HSL is degraded by the enzyme. Addition of the purified protein to P. aeruginosa PAO1 cultures completely inhibited accumulation of 3-oxo-C12-HSL and production of the signal molecule 2-heptyl-3-hydroxy-4(1H)-quinolone and reduced production of the virulence factors elastase and pyocyanin. Similar results were obtained when the PA2385 gene was overexpressed in P. aeruginosa. These results demonstrate that the protein has in situ quorum-quenching activity. The quorum-quenching AHL acylase may enable P. aeruginosa PAO1 to modulate its own quorum-sensing-dependent pathogenic potential and, moreover, offers possibilities for novel antipseudomonal therapies.

scholarly journals Efficacy of Liposomal Bismuth-Ethanedithiol-Loaded Tobramycin after Intratracheal Administration in Rats with Pulmonary Pseudomonas aeruginosa Infection

2012 ◽  
Vol 57 (1) ◽  
pp. 569-578 ◽  
Author(s):  
Moayad Alhariri ◽  
Abdelwahab Omri
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Homoserine Lactone ◽  
Protease Production ◽  
Signal Molecules ◽  
Acyl Homoserine Lactone ◽  
Signal Molecule ◽  
Intratracheal Administration ◽  
Content Type

ABSTRACTWe sought to investigate alterations in quorum-sensing signal moleculeN-acyl homoserine lactone secretion and in the release ofPseudomonas aeruginosavirulence factors, as well as thein vivoantimicrobial activity of bismuth-ethanedithiol incorporated into a liposome-loaded tobramycin formulation (LipoBiEDT-TOB) administered to rats chronically infected withP. aeruginosa. The quorum-sensing signal moleculeN-acyl homoserine lactone was monitored by using a biosensor organism.P. aeruginosavirulence factors were assessed spectrophotometrically. An agar beads model of chronicPseudomonaslung infection in rats was used to evaluate the efficacy of the liposomal formulation in the reduction of bacterial count. The levels of active tobramycin in the lungs and the kidneys were evaluated by microbiological assay. LipoBiEDT-TOB was effective in disrupting both quorum-sensing signal moleculesN-3-oxo-dodeccanoylhomoserine lactone andN-butanoylhomoserine lactone, as well as significantly (P< 0.05) reducing lipase, chitinase, and protease production. At 24 h after 3 treatments, the CFU counts in lungs of animals treated with LipoBiEDT-TOB were of 3 log10CFU/lung, comparated to 7.4 and 4.7 log10CFU/lung, respectively, in untreated lungs and in lungs treated with free antibiotic. The antibiotic concentration after the last dose of LipoBiEDT-TOB was 25.1 μg/lung, while no tobramycin was detected in the kidneys. As for the free antibiotic, we found 6.5 μg/kidney but could not detect any tobramycin in the lungs. Taken together, LipoBiEDT-TOB reduced the production of quorum-sensing molecules and virulence factors and could highly improve the management of chronic pulmonary infection in cystic fibrosis patients.

scholarly journals Chromobacterium violaceum and Pseudomonas aeruginosa PAO1: Models for Evaluating Anti-Quorum Sensing Activity of Melaleuca alternifolia Essential Oil and Its Main Component Terpinen-4-ol

Molecules ◽  
2018 ◽  
Vol 23 (10) ◽  
pp. 2672 ◽  
Author(s):  
Emira Noumi ◽  
Abderrahmen Merghni ◽  
Mousa M. Alreshidi ◽  
Ons Haddad ◽  
Gültekin Akmadar ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Essential Oil ◽  
Biofilm Formation ◽  
Chromobacterium Violaceum ◽  
Melaleuca Alternifolia ◽  
Swarming Motility ◽  
Pseudomonas Aeruginosa Pao1 ◽  
Tea Tree ◽  
Violacein Production

The problem of antibiotic resistance among pathogens encourages searching for novel active molecules. The aim of the research was to assay the anti-quorum sensing (anti-QS) and antibiofilm potential of Melaleuca alternifolia essential oil and its main constituent, terpinen-4-ol, to prevent the infections due to methicillin-resistant Staphylococcus aureus strains as an alternate to antibiotics. The tea tree oil (TTO) was evaluated for its potential in inhibiting QS-dependent phenomena such as violacein production in Chromobacterium violaceum, swarming motility of Pseudomonas aeruginosa PAO1, and biofilm formation in MRSA strains on glass. The results showed that terpinen-4-ol was able to inhibit MRSA strain biofilm formation on the glass strips by 73.70%. TTO inhibited the violacein production at a mean inhibitory concentration (MIC) value of 0.048 mg/mL by 69.3%. At 100 µg/mL TTO and terpinen-4-ol exhibited inhibition in swarming motility of PAO1 by 33.33% and 25%, respectively. TTO revealed anti-QS and anti-biofilm activities at very low concentrations, but it could be further investigated for new molecules useful for the treatment of MRSA infections.

Biofilm Formation, Communication and Interactions of Mesophilic Leaching Bacteria during Pyrite Oxidation

2013 ◽  
Vol 825 ◽  
pp. 107-110
Author(s):  
Sören Bellenberg ◽  
Robert Barthen ◽  
Mario Vera ◽  
Nicolas Guiliani ◽  
Wolfgang Sand
Keyword(s):  
Quorum Sensing ◽  
Acidithiobacillus Ferrooxidans ◽  
Biofilm Formation ◽  
Pyrite Oxidation ◽  
Cell Communication ◽  
Homoserine Lactone ◽  
Mixed Cultures ◽  
Acyl Homoserine Lactone ◽  
Leaching Bacteria ◽  
Leaching Efficiency

A functional luxIR-type Quorum Sensing (QS) system is present in Acidithiobacillus ferrooxidans. However, cell-cell communication among various acidophilic chemolithoautotrophs growing on pyrite has not been studied in detail. These aspects are the scope of this study with emphasis on the effects exerted by the N-acyl-homoserine lactone (AHL) type signaling molecules which are produced by Acidithiobacillus ferrooxidans. Their effects on attachment and leaching efficiency by other leaching bacteria, such as Acidithiobacillus ferrivorans, Acidiferrobacter spp. SPIII/3 and Leptospirillum ferrooxidans in pure and mixed cultures growing on pyrite is shown.

Influence of Glucose Concentrations on Biofilm Formation, Motility, Exoprotease Production, and Quorum Sensing in Aeromonas hydrophila

2013 ◽  
Vol 76 (2) ◽  
pp. 239-247 ◽  
Author(s):  
IQBAL KABIR JAHID ◽  
NA-YOUNG LEE ◽  
ANNA KIM ◽  
SANG-DO HA
Keyword(s):  
Quorum Sensing ◽  
Aeromonas Hydrophila ◽  
Biofilm Formation ◽  
Opportunistic Pathogen ◽  
Homoserine Lactone ◽  
Protease Production ◽  
Acyl Homoserine Lactone ◽  
Human Pathogen ◽  
Initial Biofilm ◽  
Motility Inhibition

Aeromonas hydrophila recently has received increased attention because it is opportunistic and a primary human pathogen. A. hydrophila biofilm formation and its control are a major concern for food safety because biofilms are related to virulence. Therefore, we investigated biofilm formation, motility inhibition, quorum sensing, and exoprotease production of this opportunistic pathogen in response to various glucose concentrations from 0.05 to 2.5% (wt/vol). More than 0.05% glucose significantly impaired (P &lt; 0.05) quorum sensing, biofilm formation, protease production, and swarming and swimming motility, whereas bacteria treated with 0.05% glucose had activity similar to that of the control (0% glucose). A stage shift biofilm assay revealed that the addition of glucose (2.5%) inhibited initial biofilm formation but not later stages. However, addition of quorum sensing molecules N-3-butanoyl-DL-homoserine lactone and N-3-hexanoyl homoserine lactone partially restored protease production, indicating that quorum sensing is controlled by glucose concentrations. Thus, glucose present in food or added as a preservative could regulate acyl-homoserine lactone quorum sensing molecules, which mediate biofilm formation and virulence in A. hydrophila.

scholarly journals Signal Integration in Quorum Sensing Enables Cross-Species Induction of Virulence in Pectobacterium wasabiae

mBio ◽  
2017 ◽  
Vol 8 (3) ◽  
Author(s):  
Rita S. Valente ◽  
Pol Nadal-Jimenez ◽  
André F. P. Carvalho ◽  
Filipe J. D. Vieira ◽  
Karina B. Xavier
Keyword(s):  
Signal Transduction ◽  
Quorum Sensing ◽  
Plant Pathogen ◽  
Bacterial Species ◽  
Homoserine Lactone ◽  
Signal Molecules ◽  
Acyl Homoserine Lactone ◽  
Interspecies Interactions ◽  
Major Factors

ABSTRACT Bacterial communities can sense their neighbors, regulating group behaviors in response to cell density and environmental changes. The diversity of signaling networks in a single species has been postulated to allow custom responses to different stimuli; however, little is known about how multiple signals are integrated and the implications of this integration in different ecological contexts. In the plant pathogen Pectobacterium wasabiae (formerly Erwinia carotovora), two signaling networks—the N-acyl homoserine lactone (AHL) quorum-sensing system and the Gac/Rsm signal transduction pathway—control the expression of secreted plant cell wall-degrading enzymes, its major virulence determinants. We show that the AHL system controls the Gac/Rsm system by affecting the expression of the regulatory RNA RsmB. This regulation is mediated by ExpR2, the quorum-sensing receptor that responds to the P. wasabiae cognate AHL but also to AHLs produced by other bacterial species. As a consequence, this level of regulation allows P. wasabiae to bypass the Gac-dependent regulation of RsmB in the presence of exogenous AHLs or AHL-producing bacteria. We provide in vivo evidence that this pivotal role of RsmB in signal transduction is important for the ability of P. wasabiae to induce virulence in response to other AHL-producing bacteria in multispecies plant lesions. Our results suggest that the signaling architecture in P. wasabiae was coopted to prime the bacteria to eavesdrop on other bacteria and quickly join the efforts of other species, which are already exploiting host resources. IMPORTANCE Quorum-sensing mechanisms enable bacteria to communicate through small signal molecules and coordinate group behaviors. Often, bacteria have various quorum-sensing receptors and integrate information with other signal transduction pathways, presumably allowing them to respond to different ecological contexts. The plant pathogen Pectobacterium wasabiae has two N-acyl homoserine lactone receptors with apparently the same regulatory functions. Our work revealed that the receptor with the broadest signal specificity is also responsible for establishing the link between the main signaling pathways regulating virulence in P. wasabiae. This link is essential to provide P. wasabiae with the ability to induce virulence earlier in response to higher densities of other bacterial species. We further present in vivo evidence that this novel regulatory link enables P. wasabiae to join related bacteria in the effort to degrade host tissue in multispecies plant lesions. Our work provides support for the hypothesis that interspecies interactions are among the major factors influencing the network architectures observed in bacterial quorum-sensing pathways. IMPORTANCE Quorum-sensing mechanisms enable bacteria to communicate through small signal molecules and coordinate group behaviors. Often, bacteria have various quorum-sensing receptors and integrate information with other signal transduction pathways, presumably allowing them to respond to different ecological contexts. The plant pathogen Pectobacterium wasabiae has two N-acyl homoserine lactone receptors with apparently the same regulatory functions. Our work revealed that the receptor with the broadest signal specificity is also responsible for establishing the link between the main signaling pathways regulating virulence in P. wasabiae. This link is essential to provide P. wasabiae with the ability to induce virulence earlier in response to higher densities of other bacterial species. We further present in vivo evidence that this novel regulatory link enables P. wasabiae to join related bacteria in the effort to degrade host tissue in multispecies plant lesions. Our work provides support for the hypothesis that interspecies interactions are among the major factors influencing the network architectures observed in bacterial quorum-sensing pathways.

scholarly journals Targeting Acyl Homoserine Lactone (AHL) of Pseudomonas aeruginosa Responsible for Biofilm Formation using Plant Metabolites

2019 ◽  
Vol 13 (3) ◽  
pp. 1841-1846
Author(s):  
Sree Samanvitha K ◽  
Sanjay Kumar S ◽  
Antony V. Samrot ◽  
Raji P ◽  
Ponnaiah Paulraj ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Biofilm Formation ◽  
Homoserine Lactone ◽  
Acyl Homoserine Lactone ◽  
Plant Metabolites
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