scholarly journals The YebC Family Protein PA0964 Negatively Regulates the Pseudomonas aeruginosa Quinolone Signal System and Pyocyanin Production

2008 ◽  
Vol 190 (18) ◽  
pp. 6217-6227 ◽  
Author(s):  
Haihua Liang ◽  
Lingling Li ◽  
Zhaolin Dong ◽  
Michael G. Surette ◽  
Kangmin Duan
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Response Regulator ◽  
Initial Study ◽  
Pfam Family ◽  
Swarming Motility ◽  
Sensing Systems ◽  
Family Protein ◽  
Pyocyanin Production

ABSTRACT Bacterial pathogenicity is often manifested by the expression of various cell-associated and secreted virulence factors, such as exoenzymes, protease, and toxins. In Pseudomonas aeruginosa, the expression of virulence genes is coordinately controlled by the global regulatory quorum-sensing systems, which includes the las and rhl systems as well as the Pseudomonas quinolone signal (PQS) system. Phenazine compounds are among the virulence factors under the control of both the rhl and PQS systems. In this study, regulation of the phzA1B1C1D1E1 (phzA1) operon, which is involved in phenazine synthesis, was investigated. In an initial study of inducing conditions, we observed that phzA1 was induced by subinhibitory concentrations of tetracycline. Screening of 13,000 mutants revealed 32 genes that altered phzA1 expression in the presence of subinhibitory tetracycline concentrations. Among them, the gene PA0964, designated pmpR ( p qsR-mediated P QS r egulator), has been identified as a novel regulator of the PQS system. It belongs to a large group of widespread conserved hypothetical proteins with unknown function, the YebC protein family (Pfam family DUF28). It negatively regulates the quorum-sensing response regulator pqsR of the PQS system by binding at its promoter region. Alongside phzA1 expression and phenazine and pyocyanin production, a set of virulence factors genes controlled by both rhl and the PQS were shown to be modulated by PmpR. Swarming motility and biofilm formation were also significantly affected. The results added another layer of regulation in the rather complex quorum-sensing systems in P. aeruginosa and demonstrated a clear functional clue for the YebC family proteins.

Possible antivirulent activity of some agents against clinical isolates of Pseudomonas aeruginosa

2021 ◽  
Vol 30 (2) ◽  
pp. 1-8
Author(s):  
Ahmad O. Rifai ◽  
Abeer M. Abd El-Aziz ◽  
Hany I. Kenawy
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Therapeutic Target ◽  
Inhibitory Action ◽  
Antibacterial Agents ◽  
Mechanisms Of Resistance ◽  
Life Threatening ◽  
Pheniramine Maleate ◽  
Pyocyanin Production

Background: Pseudomonas aeruginosa has developed different mechanisms of resistance against antibiotics and became one of the most life-threatening pathogens. Fighting against its virulence Factors are an alternative therapeutic target. Objective: This study was directed towards the investigation of anti-quorum sensing activity and inhibitory action on virulence factors of different agents including antibacterial agents to which Pseudomonas aeruginosa isolates are resistant and non-antibacterial agents. Methodology: Anti-quorum sensing activity of ceftriaxone, ceftazidime (CAZ), cefepime (FEP), vancomycin (VA), paracetamol (PA), and pheniramine maleate (PHE) investigated as well as their ability to reduce other virulence factors including protease, hemolysin, and pyocyanin production. Results: This study showed that 3rd and 4th generations cephalosporins could be used as anti-quorum sensing agents effectively in the treatment of Pseudomonas aeruginosa infections, however, vancomycin, paracetamol, and pheniramine maleate had no effect on inhibiting the studied virulence factors. Conclusion: From our study we conclude that although cephalosporins at the used concentrations did not show anti-pseudomonal activity they were effective as anti virulent agents that could be utilized in therapeutically in controlling Pseudomonas aeruginosa infections.

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 In Silico and In Vitro Screening of Antipathogenic Properties of Melianthus comosus (Vahl) against Pseudomonas aeruginosa

Antibiotics ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 679
Author(s):  
Itumeleng T. Baloyi ◽  
Idowu J. Adeosun ◽  
Abdullahi A. Yusuf ◽  
Sekelwa Cosa
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Cell Attachment ◽  
Bacterial Colonization ◽  
Plant Secondary Metabolites ◽  
Diethyl Ester ◽  
Human Pathogens ◽  
Swarming Motility ◽  
Biofilm Development

Bacterial quorum sensing (QS) system regulates pathogenesis, virulence, and biofilm formation, and together they contribute to nosocomial infections. Opportunistic pathogens, such as Pseudomonas aeruginosa, rely on QS for regulating virulence factors. Therefore, blocking the QS system may aid management of various infectious diseases caused by human pathogens. Plant secondary metabolites can thwart bacterial colonization and virulence. As such, this study was undertaken to evaluate three extracts from the medicinal plant, Melianthus comosus, from which phytochemical compounds were identified with potential to inhibit QS-dependent virulence factors in P. aeruginosa. Chemical profiling of the three extracts identified 1,2-benzene dicarboxylic acid, diethyl ester, neophytadiene and hexadecanoic acid as the common compounds. Validation of antibacterial activity confirmed the same MIC values of 0.78 mg/mL for aqueous, methanol and dichloromethane extracts while selected guanosine showed MIC 0.031 mg/mL. Molecular docking analysis showed anti-quorum sensing (AQS) potential of guanosine binding to CviR’ and 2UV0 proteins with varying docking scores of −5.969 and −8.376 kcal/mol, respectively. Guanosine inhibited biofilm cell attachment and biofilm development at 78.88% and 34.85%, respectively. Significant swimming and swarming motility restriction of P. aeruginosa were observed at the highest concentration of plant extracts and guanosine. Overall, guanosine revealed the best swarming motility restrictions. M. comosus extracts and guanosine have shown clear antibacterial effects and subsequent reduction of QS-dependent virulence activities against P.aeruginosa. Therefore, they could be ideal candidates in the search for antipathogenic drugs to combat P.aeruginosa infections.

scholarly journals Evaluation of Anti-quorum Sensing Potential of Saraca asoca (Family Caesalpiniaceae) against Chromobacterium violaceum and Pseudomonas aeruginosa PA01

2021 ◽  
pp. 71-82
Author(s):  
B. S. Paliya ◽  
J. Mathew ◽  
B. N. Singh
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Test Sample ◽  
Stem Bark ◽  
Chromobacterium Violaceum ◽  
Broth Culture ◽  
Bark Extract ◽  
Swarming Motility ◽  
Saraca Asoca

Aim: The present study was performed to evaluate the anti-quorum sensing (QS) potential of traditional medicinal herb Saracaasoca (family Caesalpiniaceae) stem bark extract against Chromobacterium violaceum and Pseudomonas aeruginosa PA01. Study Design: First, the test sample (bark extract) was screened for anti-QS activity. Then systematic in-vitro and biochemical tests were performed to evaluate the effect of the test sample on the QS mediated virulence factors. Place and Duration of Study: All the experimental works were performed in Lab 311, pharmacology division, CSIR-NBRI Lucknow from June 2019 to October 2019. Methodology: The samples of Saraca asoca stem bark were washed, dried and extracted using 70% methanol. The minimum inhibitory concentration (MIC) of the prepared Sarca asoca bark extract was determined using the Alamar blue assay, and the anti-QS activity was screened using standard agar overlay method against CV 12472 at subinhibitory concentrations 100, 200 and 300 µg (< MIC value). SAE effect on biofilms formation was assessed by growing biofilms on glass slides in a static culture of PA01. Anti-virulence effect of SAE on the production of QS-regulated virulence factors such as Pyocyanin, proteases, elastases, rhamnolipid and alginate in Pseudomonas aeruginosa was determined using the supernatant of a 24 hours old broth culture of PA01 supplemented with SAE. Using the agar plate technique, the swimming and swarming motility assays were conducted on 0.3% and 0.5% agar plates respectively. One-way ANOVA was used to analyze the data, presented as mean ± SD (standard deviation) of three independent experiments. Results: Preliminary screening results showed significant QS inhibition against CV 12472 in an agar overlay disk diffusion assay in a concentration-dependent manner. Data from the biofilm assay showed loose, distorted, irregular PA01 biofilm formation at 200 µg (48%) and 300 µg (65%). SAE caused a significant drop in virulence factor production, with maximum reduction in pyocyanin (58%), proteases (67%), elastases (52%), rhamnolipid (53%), and alginate (44%) observed at 300 µg concentration. At SAE sub-lethal concentrations (200 and 300 µg), both the swimming and swarming motility of PA01 were significantly inhibited. Conclusions: The present study demonstrates the broad-spectrum anti-QS potential of SAE, reported for the first time, suggesting that SAE could be considered as an alternative herbal source to develop antimicrobial agents which can be either solitary or synergistically with conventional antimicrobial drugs.

scholarly journals Molecular Mechanisms of Phosphate Stress Activation of Pseudomonas aeruginosa Quorum Sensing Systems

mSphere ◽  
2020 ◽  
Vol 5 (2) ◽  
Author(s):  
Xianfa Meng ◽  
Stephen Dela Ahator ◽  
Lian-Hui Zhang
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Response Regulator ◽  
Regulatory System ◽  
Regulatory Genes ◽  
Phosphate Deficiency ◽  
Content Type ◽  
Sensing Systems ◽  
Two Component ◽  
Phosphate Depletion

ABSTRACT The hierarchical quorum sensing (QS) systems of Pseudomonas aeruginosa, consisting of las, pqs, and rhl, coordinate the expression of bacterial virulence genes. Previous studies showed that under phosphate deficiency conditions, two-component regulatory system PhoRB could activate various genes involved in cytotoxicity through modulation of QS systems, but the mechanism by which PhoR/PhoB influences QS remains largely unknown. Here, we provide evidence that among the key QS regulatory genes in P. aeruginosa, rhlR, pqsA, mvfR, and lasI were activated by the response regulator PhoB under phosphate-depleted conditions. We show that PhoB is a strong competitor against LasR and RsaL for binding to the promoter of lasI and induces significant expression of lasI, rhlR, and mvfR. However, expression of lasI, encoding the signal 3-oxo-C12-HSL, was increased only marginally under the same phosphate-depleted conditions. This seeming inconsistency was attributed to the induction of pvdQ, which encodes an enzyme for degradation of 3-oxo-C12-HSL signal molecules. Taken together, the results from this study demonstrate that through the two-component regulatory system PhoR/PhoB, phosphate depletion stress could influence the QS network by modulating several key regulators, including lasI, rhlR, mvfR, and pvdQ. The findings highlight not only the potency of the PhoR/PhoB-mediated bacterial stress response mechanism but also the plasticity of the P. aeruginosa QS systems in coping with the changed environmental conditions. IMPORTANCE It is not fully understood how phosphate deficiency could influence the virulence of Pseudomonas aeruginosa through modulation of the bacterial QS systems. This report presents a systemic investigation on the impact of phosphate depletion on the hierarchy of quorum sensing systems of P. aeruginosa. The results showed that phosphate stress could have an extensive impact on the QS networks of this bacterial pathogen. Among the 7 QS regulatory genes representing the 3 sets of QS systems tested, 4 were significantly upregulated by phosphate depletion stress through the PhoR/PhoB two-component regulatory system, especially the upstream QS regulatory gene lasI. We also present evidence that the response regulator PhoB was a strong competitor against the las regulators LasR and RsaL for the lasI promoter, unveiling the mechanistic basis of the process by which phosphate stress could modulate the bacterial QS systems.

scholarly journals Correlation of quorum sensing and virulence factors in Pseudomonas aeruginosa isolates in Egypt

2015 ◽  
Vol 9 (10) ◽  
pp. 1091-1099 ◽  
Author(s):  
Hamida M. Aboushleib ◽  
Hoda M. Omar ◽  
Rania Abozahra ◽  
Amel Elsheredy ◽  
Kholoud Baraka
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Biofilm Formation ◽  
Point Mutations ◽  
Inhibitory Effect ◽  
Clinical Isolates ◽  
Clove Oil ◽  
Twitching Motility ◽  
Pyocyanin Production

Introduction: Pseudomonas aeruginosa is one of the most virulent nosocomial pathogens worldwide. Quorum sensing (QS) regulates the production of pathogenic virulence factors and biofilm formation in P. aeruginosa. The four genes lasR, lasI, rhlR,and rhlI were found to regulate this QS system. In this study, we aimed to assess the correlation between these four genes and QS-dependent virulence factors and to detect the inhibitory effect of clove oil on QS. Methodology: Fifty P. aeruginosa clinical isolates were collected. Susceptibility to different antibiotics was tested. Virulence factors including biofilm formation, pyocyanin production, and twitching motility were phenotypically detected. QS genes were amplified by polymerase chain reaction (PCR), and one strain subsequently underwent sequencing. The inhibitory effect of clove oil on virulence factors was also tested. Results: A positive correlation was found between biofilm formation and the presence of lasR and rhlI genes. Twitching motility was positively correlated with the presence of lasR, lasI, and rhlI genes. On the other hand, no correlation was found between pyocyanin production and any of the studied genes. Only one isolate amplified all the tested QS gene primers, but it did not express any of the tested virulence factors phenotypically. Sequence analyses of this isolate showed that the four genes had point mutations. Conclusions: Results emphasize the importance of QS in P. aeruginosa virulence; however, QS-deficient clinical isolates occur and are still capable of causing clinical infections in humans. Also, clove oil has an obvious inhibitory effect on QS, which should be clinically exploited.

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