scholarly journals Inhibition of Virulence Factors and Biofilm Formation by Wogonin Attenuates Pathogenicity of Pseudomonas aeruginosa PAO1 via Targeting pqs Quorum-Sensing System

2021 ◽  
Vol 22 (23) ◽  
pp. 12699
Author(s):  
Shiwei Wang ◽  
Yuqi Feng ◽  
Xiaofeng Han ◽  
Xinyu Cai ◽  
Liu Yang ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Biofilm Formation ◽  
Extracellular Polysaccharide ◽  
Fruit Fly ◽  
Opportunistic Pathogen ◽  
Signal Molecule ◽  
Conventional Antibiotics

Pseudomonas aeruginosa, an important opportunistic pathogen, is capable of producing various virulence factors and forming biofilm that are regulated by quorum sensing (QS). It is known that targeting virulence factor production and biofilm formation instead of exerting selective pressure on growth such as conventional antibiotics can reduce multidrug resistance in bacteria. Therefore, many quorum-sensing inhibitors (QSIs) have been developed to prevent or treat this bacterial infection. In this study, wogonin, as an active ingredient from Agrimonia pilosa, was found to be able to inhibit QS system of P. aeruginosa PAO1. Wogonin downregulated the expression of QS-related genes and reduced the production of many virulence factors, such as elastase, pyocyanin, and proteolytic enzyme. In addition, wogonin decreased the extracellular polysaccharide synthesis and inhibited twitching, swimming, and swarming motilities and biofilm formation. The attenuation of pathogenicity in P. aeruginosa PAO1 by wogonin application was further validated in vivo by cabbage infection and fruit fly and nematode survival experiments. Further molecular docking analysis, pathogenicity examination of various QS-related mutants, and PQS signal molecule detection revealed that wogonin could interfere with PQS signal molecular synthesis by affecting pqsA and pqsR. Taken together, the results indicated that wogonin might be used as an anti-QS candidate drug to attenuate the infection caused by P. aeruginosa.

scholarly journals Plantain Herb Extracts significantly attenuate the quorum sensing-controlled virulence factors and inhibit biofilm formation in Pseudomonas aeruginosa PAO1

2019 ◽  
Vol 78 ◽  
pp. 01004
Author(s):  
Shan Li ◽  
Jiangning Yao ◽  
Haoming Li
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Biofilm Formation ◽  
Opportunistic Pathogen ◽  
Significant Inhibition ◽  
Control Group ◽  
Produce Cell ◽  
Group B ◽  
Herb Extracts

Pseudomonas aeruginosa is a Gram-negative organism that can survive under harsh conditions, and it is also an opportunistic pathogen that can produce cell-associated extracellular virulence factors. Several of these virulence factors have been demonstrated to be regulated by quorum sensing (QS). Plantain Herb has been used as antibacterial agents for many centuries in China. In this study, we analyzed Plantain Herb Extracts (PHE) at the concentration of 16 μg/mL (Group A, MIC), 8 μg/mL (Group B, 1/2 MIC) and 4 μg/mL (Group C, 1/4 MIC) for inhibition of the virulence factors production and biofilm formation in P. aeruginosa PAO1. The virulence factors included pyocyanin, rhamnolipids, protease and alginate. PHE showed significant inhibition of virulence factors as compared to the control group without interfering its growth. Thus, PHE might be a potent QS inhibitor and anti-biofilm agent in the treatment of Pseudomonas aeruginosa infections.

scholarly journals Cephalosporins target quorum sensing and suppress virulence of Pseudomonas aeruginosa in Caenorhabditis elegans infection model

2020 ◽  
Author(s):  
Lokender Kumar ◽  
Nathanael Brenner ◽  
John Brice ◽  
Judith Klein-Seetharaman ◽  
Susanta K. Sarkar
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Caenorhabditis Elegans ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Biofilm Formation ◽  
Host Cells ◽  
Infection Model ◽  
Host Immune System ◽  
Bacterial Cells

ABSTRACTPseudomonas aeruginosa utilizes a chemical social networking system referred to as quorum sensing (QS) to strategically co-ordinate the expression of virulence factors and biofilm formation. Virulence attributes damage the host cells, impair the host immune system, and protect bacterial cells from antibiotic attack. Thus, anti-QS agents may act as novel anti-infective therapeutics to treat P. aeruginosa infections. The present study was performed to evaluate the anti-QS, anti-biofilm, and anti-virulence activity of β-lactam antibiotics (carbapenems and cephalosporins) against P. aeruginosa. The anti-QS activity was quantified using Chromobacterium violaceum CV026 as a QS reporter strain. Our results showed that cephalosporins including cefepime (CP), ceftazidime (CF), and ceftriaxone (CT) exhibited potent anti-QS and anti-virulence activities against P. aeruginosa PAO1. These antibiotics significantly impaired motility phenotypes, decreased pyocyanin production, and reduced the biofilm formation by P. aeruginosa PAO1. In the present study, we studied isogenic QS mutants of PAO1: ΔLasR, ΔRhlR, ΔPqsA, and ΔPqsR and found that the levels of virulence factors of antibiotic-treated PAO1 were comparable to QS mutant strains. Molecular docking predicted high binding affinities of cephalosporins for the ligand-binding pocket of QS receptors (CviR, LasR, and PqsR). In addition, our results showed that the anti-microbial activity of aminoglycosides increased in the presence of sub-inhibitory concentrations (sub-MICs) of CP against P. aeruginosa PAO1. Further, utilizing Caenorhabditis elegans as an animal model for the in vivo anti-virulence effects of antibiotics, cephalosporins showed a significant increase in C. elegans survival by suppressing virulence factor production in P. aeruginosa. Thus, our results indicate that cephalosporins might provide a viable anti-virulence therapy in the treatment of infections caused by multi-drug resistant P. aeruginosa.

Terpinen-4-ol attenuates quorum sensing regulated virulence factors and biofilm formation in Pseudomonas aeruginosa

2020 ◽  
Vol 15 (2) ◽  
pp. 127-142 ◽  
Author(s):  
Sunil K Bose ◽  
Monika Chauhan ◽  
Neelima Dhingra ◽  
Sanjay Chhibber ◽  
Kusum Harjai
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Molecular Docking ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Biofilm Formation ◽  
Treatment Strategies ◽  
In Vivo Evaluation ◽  
Docking Analysis ◽  
Molecular Docking Analysis

Aim: To investigate the effects of Terpinen-4-ol on quorum sensing (QS)-regulated biofilm formation and virulence factors production in Pseudomonas aeruginosa. Materials & methods: QS inhibition, molecular docking analysis and gene expression studies were performed to check attenuation effect of Terpinen-4-ol on virulence of P. aeruginosa. Production of various virulence factors and biofilm formation were studied at sub-MIC of Terpinen-4-ol alone and in combination with ciprofloxacin. Results: Terpinen-4-ol at sub-MIC exhibited QS inhibition and downregulated all key QS genes. Molecular docking analysis showed high binding affinities of Terpinen-4-ol with QS receptors. Terpinen-4-ol exhibited synergistic interaction with ciprofloxacin and further reduced production of all the virulence factors and biofilms formation. Conclusion: Terpinen-4-ol could be developed into antivirulence drug after its in vivo evaluation for treatment strategies.

scholarly journals Quorum Sensing Inhibitory Activities of Oridonin in Pseudomonas Aeruginosa

2021 ◽  
Vol 233 ◽  
pp. 02044
Author(s):  
Jing Huang ◽  
Haoming Li
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Biofilm Formation ◽  
Opportunistic Pathogen ◽  
Active Components ◽  
Produce Cell ◽  
Potential Strategy ◽  
Rabdosia Rubescens ◽  
Infective Agent

Pseudomonas aeruginosa is an opportunistic pathogen, and it can produce cell-associated and extracellular virulence factors. Several of these virulence factors have been demonstrated to be regulated by quorum sensing (QS). Disabling QS system with anti-infective agent is considered as a potential strategy to prevent bacterial infection. Rabdosia rubescens has been used as antibacterial agents for many centuries in China. In this study, Oridonin, the major active components of Rabdosia rubescens, was tested for QS inhibition in Pseudomonas aeruginosa. QS inhibitory activity is demonstrated by reduction in pyocyanin (58.4%), rhamnolipids (64.3%), elastase (58.6%), and protease (49.1%) in Pseudomonas aeruginosa PAO1 at 125 µg/ml (MIC) concentration. Biofilm formation by Pseudomonas aeruginosa PAO1 was reduced considerably (40.3-57.7%) over control. These findings suggest that Oridonin might be a potent Quorum Sensing Inhibitor (QSI) and anti-biofilm agent in the treatment of Pseudomonas aeruginosa infections.

scholarly journals Paeonol Attenuates Quorum-Sensing Regulated Virulence and Biofilm Formation in Pseudomonas aeruginosa

2021 ◽  
Vol 12 ◽  
Author(s):  
Dan Yang ◽  
Suqi Hao ◽  
Ling Zhao ◽  
Fei Shi ◽  
Gang Ye ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Biofilm Formation ◽  
Resistant Bacteria ◽  
Infection Model ◽  
Dependent Manner ◽  
Gram Negative ◽  
C Elegans

With the prevalence of multidrug-resistant bacteria and clinical -acquired pathogenic infections, the development of quorum-sensing (QS) interfering agents is one of the most potential strategies to combat bacterial infections and antibiotic resistance. Chinese herbal medicines constitute a valuable bank of resources for the identification of QS inhibitors. Accordingly, in this research, some compounds were tested for QS inhibition using indicator strains. Paeonol is a phenolic compound, which can effectively reduce the production of violacein without affecting its growth in Chromobacterium violaceum ATCC 12472, indicating its excellent anti-QS activity. This study assessed the anti-biofilm activity of paeonol against Gram-negative pathogens and investigated the effect of paeonol on QS-regulated virulence factors in Pseudomonas aeruginosa. A Caenorhabditis elegans infection model was used to explore the anti-infection ability of paeonol in vivo. Paeonol exhibited an effective anti-biofilm activity against Gram-negative bacteria. The ability of paeonol to interfere with the AHL-mediated quorum sensing systems of P. aeruginosa was determined, found that it could attenuate biofilm formation, and synthesis of pyocyanin, protease, elastase, motility, and AHL signaling molecule in a concentration- and time-dependent manner. Moreover, paeonol could significantly downregulate the transcription level of the QS-related genes of P. aeruginosa including lasI/R, rhlI/R, pqs/mvfR, as well as mediated its virulence factors, lasA, lasB, rhlA, rhlC, phzA, phzM, phzH, and phzS. In vivo studies revealed that paeonol could reduce the pathogenicity of P. aeruginosa and enhance the survival rate of C. elegans, showing a moderate protective effect on C. elegans. Collectively, these findings suggest that paeonol attenuates bacterial virulence and infection of P. aeruginosa and that further research elucidating the anti-QS mechanism of this compound in vivo is warranted.

Pseudomonas aeruginosa tolerance to tobramycin, hydrogen peroxide and polymorphonuclear leukocytes is quorum-sensing dependent

Microbiology ◽  
2005 ◽  
Vol 151 (2) ◽  
pp. 373-383 ◽  
Author(s):  
Thomas Bjarnsholt ◽  
Peter Østrup Jensen ◽  
Mette Burmølle ◽  
Morten Hentzer ◽  
Janus A. J. Haagensen ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Polymorphonuclear Leukocytes ◽  
Present Report ◽  
Cell Communication ◽  
A Cell ◽  
Opportunistic Human Pathogen ◽  
Conventional Antibiotics

The opportunistic human pathogen Pseudomonas aeruginosa is the predominant micro-organism of chronic lung infections in cystic fibrosis (CF) patients. P. aeruginosa colonizes the CF lungs by forming biofilm structures in the alveoli. In the biofilm mode of growth the bacteria are highly tolerant to otherwise lethal doses of antibiotics and are protected from bactericidal activity of polymorphonuclear leukocytes (PMNs). P. aeruginosa controls the expression of many of its virulence factors by means of a cell–cell communication system termed quorum sensing (QS). In the present report it is demonstrated that biofilm bacteria in which QS is blocked either by mutation or by administration of QS inhibitory drugs are sensitive to treatment with tobramycin and H2O2, and are readily phagocytosed by PMNs, in contrast to bacteria with functional QS systems. In contrast to the wild-type, QS-deficient biofilms led to an immediate respiratory-burst activation of the PMNs in vitro. In vivo QS-deficient mutants provoked a higher degree of inflammation. It is suggested that quorum signals and QS-inhibitory drugs play direct and opposite roles in this process. Consequently, the faster and highly efficient clearance of QS-deficient bacteria in vivo is probably a two-sided phenomenon: down regulation of virulence and activation of the innate immune system. These data also suggest that a combination of the action of PMNs and QS inhibitors along with conventional antibiotics would eliminate the biofilm-forming bacteria before a chronic infection is established.

scholarly journals Inhibition of Quorum Sensing in Pseudomonas aeruginosa by N-Acyl Cyclopentylamides

2007 ◽  
Vol 73 (10) ◽  
pp. 3183-3188 ◽  
Author(s):  
Takenori Ishida ◽  
Tsukasa Ikeda ◽  
Noboru Takiguchi ◽  
Akio Kuroda ◽  
Hisao Ohtake ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Biofilm Formation ◽  
Homoserine Lactone ◽  
Ring Structure ◽  
Response Regulators ◽  
Maximal Inhibition ◽  
Sensing Systems ◽  
Reporter Assays

ABSTRACT N-Octanoyl cyclopentylamide (C8-CPA) was found to moderately inhibit quorum sensing in Pseudomonas aeruginosa PAO1. To obtain more powerful inhibitors, a series of structural analogs of C8-CPA were synthesized and examined for their ability to inhibit quorum sensing in P. aeruginosa PAO1. The lasB-lacZ and rhlA-lacZ reporter assays revealed that the chain length and the ring structure were critical for C8-CPA analogs to inhibit quorum sensing. N-Decanoyl cyclopentylamide (C10-CPA) was found to be the strongest inhibitor, and its concentrations required for half-maximal inhibition for lasB-lacZ and rhlA-lacZ expression were 80 and 90 μM, respectively. C10-CPA also inhibited production of virulence factors, including elastase, pyocyanin, and rhamnolipid, and biofilm formation without affecting growth of P. aeruginosa PAO1. C10-CPA inhibited induction of both lasI-lacZ by N-(3-oxododecanoyl)-l-homoserine lactone (PAI1) and rhlA-lacZ by N-butanoyl-l-homoserine lactone (PAI2) in the lasI rhlI mutant of P. aeruginosa PAO1, indicating that C10-CPA interferes with the las and rhl quorum-sensing systems via inhibiting interaction between their response regulators (LasR and RhlR) and autoinducers.

scholarly journals Trp-Containing Antibacterial Peptides Impair Quorum Sensing and Biofilm Development in Multidrug-Resistant Pseudomonas aeruginosa and Exhibit Synergistic Effects With Antibiotics

2021 ◽  
Vol 12 ◽  
Author(s):  
Dejing Shang ◽  
Xue Han ◽  
Wanying Du ◽  
Zhiru Kou ◽  
Fengquan Jiang
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Antibacterial Activity ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Biofilm Formation ◽  
Efflux Pump ◽  
Synergistic Effects ◽  
Multidrug Resistant ◽  
Biofilm Development ◽  
Antibiotic Efflux

Pseudomonas aeruginosa uses quorum sensing (QS) to control virulence, biofilm formation and antibiotic efflux pump expression. The development of effective small molecules targeting the QS system and biofilm formation represents a novel attractive strategy. In this present study, the effects of a series of Trp-containing peptides on the QS-regulated virulence and biofilm development of multidrug-resistant P. aeruginosa, as well as their synergistic antibacterial activity with three classes of traditional chemical antibiotics were investigated. The results showed that Trp-containing peptides at low concentrations reduced the production of QS-regulated virulence factors by downregulating the gene expression of both the las and rhl systems in the strain MRPA0108. Biofilm formation was inhibited in a concentration-dependent manner, which was associated with extracellular polysaccharide production inhibition by downregulating pelA, algD, and pslA transcription. These changes correlated with alterations in the extracellular production of pseudomonal virulence factors and swarming motility. In addition, the combination of Trp-containing peptides at low concentration with the antibiotics ceftazidime and piperacillin provided synergistic effects. Notably, L11W and L12W showed the highest synergy with ceftazidime and piperacillin. A mechanistic study demonstrated that the Trp-containing peptides, especially L12W, significantly decreased β-lactamase activity and expression of efflux pump genes OprM, MexX, and MexA, resulting in a reduction in antibiotic efflux from MRPA0108 cells and thus increasing the antibacterial activity of these antibiotics against MRPA0108.

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