scholarly journals Effect of azithromycin and phenylalanine-arginine beta-naphthylamide on quorum sensing and virulence factors in clinical isolates of Pseudomonas aeruginosa

2021 ◽  
Author(s):  
Amel Elsheredy ◽  
Ingy El-Soudany ◽  
Eglal Elsherbini ◽  
Dalia Metwally ◽  
Abeer Ghazal
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Efflux Pump ◽  
Cell Communication ◽  
Inhibitory Effect ◽  
Resistance Rate ◽  
Clinical Isolates ◽  
Efflux Pump Inhibitor ◽  
Bacteria Growth

Background and Objectives: Pseudomonas aeruginosa is a problematic opportunistic pathogen causing several types of nosocomial infections with a high resistance rate to antibiotics. Production of many virulence factors in P. aeruginosa is regulated by quorum sensing (QS), a cell-to-cell communication mechanism. In this study, we aimed to assess and compare the inhibitory effect of azithromycin (AZM) and EPI- PAβN (efflux pump inhibitor- Phenylalanine-Arginine Beta-Naphthylamide) on QS system and QS-dependent virulence factors in P. aeruginosa clinical isolates. Materials and Methods: A total of 50 P. aeruginosa isolates were obtained from different types of clinical specimens. Isolates were investigated for detection of QS system molecules by AHL cross-feeding bioassay and QS-dependent virulence factors; this was also confirmed by detection of QS genes (lasR, lasI, rhlR, and rhlI) using PCR assay. The inhibitory effect of sub-MIC AZM and EPI PAβN on these virulence factors was assessed. Results: All the P. aeruginosa, producing QS signals C4 HSL, failed to produce C4 HSL in the presence of sub-MIC AZM, In the presence of EPI PAβN (20 µg/ml) only 14 isolates were affected, there was a significant reduction in QS-dependent virulence factors production (protease, biofilm, rhamnolipid and pyocyanin) in the presence of either 20 µg/ml EPI or subMIC of AZM with the inhibitory effect of AZM was more observed than PAβN. Conclusion: Anti-QS agents like AZM and EPI (PAβN) are useful therapeutic options for P. aeruginosa due to its inhibitory effect on QS-dependent virulence factors production without selective pressure on bacteria growth, so resistance to these agents is less likely to develop.

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.

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.

scholarly journals Quorum Sensing Inhibiting Activity of Cefoperazone and Its Metallic Derivatives on Pseudomonas aeruginosa

2021 ◽  
Vol 11 ◽  
Author(s):  
Nourhan G. Naga ◽  
Dalia E. El-Badan ◽  
Heba S. Rateb ◽  
Khaled M. Ghanem ◽  
Mona I. Shaaban
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Molecular Docking ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Cobalt Complex ◽  
Inhibitory Effect ◽  
Iron Complex ◽  
Dilution Method ◽  
Docking Analysis ◽  
Molecular Docking Analysis

The last decade has witnessed a massive increase in the rate of mortalities caused by multidrug-resistant Pseudomonas aeruginosa. Therefore, developing new strategies to control virulence factors and pathogenicity has received much attention. One of these strategies is quorum sensing inhibition (QSI) which was developed to control Pseudomonas infection. This study aims to validate the effect of one of the most used β-lactam antibiotics; cefoperazone (CFP) and its metallic-derivatives on quorum sensing (QS) and virulence factors of P. aeruginosa. Assessment of quorum sensing inhibitory activity of CFP, cefoperazone Iron complex (CFPF) and cefoperazone Cobalt complex (CFPC) was performed by using reporter strain Chromobacterium violaceum ATCC 12472. Minimal inhibitory concentration (MIC) was carried out by the microbroth dilution method. The influence of sub-MICs (1/4 and 1/2 MICs) of CFP, CFPF and CFPC on virulence factors of P. aeruginosa was evaluated. Data was confirmed on the molecular level by RT-PCR. Also, molecular docking analysis was conducted to figure out the possible mechanisms of QSI. CFP, CFPF, and CFPC inhibited violacein pigment production of C. violaceum ATCC 12472. Sub-MICs of CFP (128- 256 μg/mL), and significantly low concentrations of CFPC (0.5- 16 μg/mL) and CFPF (0.5- 64 μg/mL) reduced the production of QS related virulence factors such as pyocyanin, protease, hemolysin and eliminated biofilm assembly by P. aeruginosa standard strains PAO1 and PA14, and P. aeruginosa clinical isolates Ps1, Ps2, and Ps3, without affecting bacterial viability. In addition, CFP, CFPF, and CFPC significantly reduced the expression of lasI and rhlI genes. The molecular docking analysis elucidated that the QS inhibitory effect was possibly caused by the interaction with QS receptors. Both CFPF and CFPC interacted strongly with LasI, LasR and PqsR receptors with a much high ICM scores compared to CFP that could be the cause of elimination of natural ligand binding. Therefore, CFPC and CFPF are potent inhibitors of quorum sensing signaling and virulence factors of P. aeruginosa.

scholarly journals Quorum sensing and virulence of Pseudomonas aeruginosa during urinary tract infections

2012 ◽  
Vol 6 (06) ◽  
pp. 501-507 ◽  
Author(s):  
Sezgi Senturk ◽  
Seyhan Ulusoy ◽  
Gulgun Bosgelmez-Tinaz ◽  
Aysegul Yagci
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Urinary Tract ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Urinary Tract Infections ◽  
Clinical Isolates ◽  
Pcr Analysis ◽  
Signal Molecules ◽  
Tract Infections

Introduction: In the opportunistic pathogen Pseudomonas aeruginosa, the production of several virulence factors depends on quorum sensing (QS) involving N-acylhomoserine lactone signal molecules. In vitro studies have suggested that the QS system is crucial in the pathogenesis of P. aeruginosa. However, it is unclear whether QS systems of P. aeruginosa play the same role during infections. Methodology:  In this study, to explore the contribution of QS systems to the pathogenesis of P. aeruginosa during urinary tract infections, we collected 82 clinical isolates. Detection of N-acyl-homoserine lactones (C12-HSL and C4-HSL) was performed on agar plates employing biosensor strains C. violaceum. Elastase and biofilm production were determined spectrophotometrically. QS genes were detected by PCR and subsequently underwent sequencing. Results and conclusion:  Six isolates were found to be negative in the production of both C12-HSL and C4-HSL and all virulence factors tested.  PCR analysis of these isolates revealed that four isolates contained all four QS genes while one isolate was negative for lasR gene, and one isolate negative for lasI, lasR and rhlR genes. Sequence analyses of these isolates showed that the lasR, lasI, rhlR and rhlI genes had point mutations. The combination of these mutations probably explains their C12-HSL, C4-HSL and virulence factor deficiencies. Results of this study suggest that QS deficient clinical isolates occur and are still capable of causing clinical infections in humans. 

scholarly journals Cladodionen Is a Potential Quorum Sensing Inhibitor Against Pseudomonas aeruginosa

Marine Drugs ◽  
2020 ◽  
Vol 18 (4) ◽  
pp. 205 ◽  
Author(s):  
Mengjia Wang ◽  
Lu Zhao ◽  
Hao Wu ◽  
Chaoyue Zhao ◽  
Qianhong Gong ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Binding Affinity ◽  
Virulence Factors ◽  
Jiaozhou Bay ◽  
Opportunistic Pathogen ◽  
Inhibitory Effect ◽  
Marine Fungus ◽  
Docking Analysis ◽  
Novel Approach

Pseudomonas aeruginosa is an opportunistic pathogen using virulence factors and biofilm regulated by quorum sensing (QS) systems to infect patients and protect itself from environmental stress and antibiotics. Interfering with QS systems is a novel approach to combat P. aeruginosa infections without killing the bacteria, meaning that it is much harder for bacteria to develop drug resistance. A marine fungus Cladosporium sp. Z148 with anti-QS activity was obtained from Jiaozhou Bay, China. Cladodionen, a novel QS inhibitor, was isolated from the extracts of this fungus. Cladodionen had a better inhibitory effect than pyocyanin on the production of elastase and rhamnolipid. It also inhibited biofilm formation and motilities. The mRNA expressions of QS-related genes, including receptor proteins (lasR, rhlR and pqsR), autoinducer synthases (lasI, rhlI and pqsA) and virulence factors (lasB and rhlA) were down-regulated by cladodionen. Molecular docking analysis showed that cladodionen had better binding affinity to LasR and PqsR than natural ligands. Moreover, the binding affinity of cladodionen to LasR was higher than to PqsR. Cladodionen exhibits potential as a QS inhibitor against P. aeruginosa, and its structure–activity relationships should be further studied to illustrate the mode of action, optimize its structure and improve anti-QS activity.

scholarly journals Traditional Chinese Medicine Tanreqing Inhibits Quorum Sensing Systems in Pseudomonas aeruginosa

2020 ◽  
Vol 11 ◽  
Author(s):  
Weifeng Yang ◽  
Qing Wei ◽  
Qian Tong ◽  
Kaiyu Cui ◽  
Gaiying He ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Bacterial Infections ◽  
Cell Communication ◽  
Opportunistic Pathogen ◽  
Communication Process ◽  
Phenotypic Analysis

Pseudomonas aeruginosa is an opportunistic pathogen that can infect a wide variety of hosts including humans, plants, and animals. The production of virulence factors is the determinant of the infection paradigm and is under orchestrated regulation via cell-to-cell communication process called quorum sensing (QS). To disable QS circuits and prevent bacterial infections, a large battery of anti-QS agents, particularly from traditional Chinese medicine have been developed. Here, we used P. aeruginosa as a model microorganism to investigate the effect of traditional Chinese medicine Tanreqing (TRQ) formula on bacterial pathogenicity. Phenotypic analysis showed that TRQ treatment could completely inhibit the production of phenazine pyocyanin and moderately inhibit the production of virulence factors such as rhamnolipids, elastase, and alkaline protease. Further transcriptomic analyses revealed that TRQ treatment could significantly attenuate the expression of QS-regulated genes in P. aeruginosa and TRQ-treated P. aeruginosa regulon shared a large overlap with QS regulon. Component contribution to QS inhibition shed light on the indispensable role of all five components in TRQ formula. Further genetic analysis indicated that upstream regulators of QS systems, including two-component systems GacS/GacA and PprA/PprB, were both inhibited by TRQ treatment. Finally, our TRQ formula could efficiently protect Caenorhabditis elegans from killing by P. aeruginosa. Altogether, we have proved TRQ formula as an effective and specific agent to attenuate bacterial virulence and combat bacterial infections.

scholarly journals Effect of chitosan nanoparticles on quorum sensing-controlled virulence factors and expression of LasI and RhlI genes among Pseudomonas aeruginosa clinical isolates

2021 ◽  
Vol 7 (4) ◽  
pp. 415-430
Author(s):  
Rana Abdel Fattah Abdel Fattah ◽  
◽  
Fatma El zaharaa Youssef Fathy ◽  
Tahany Abdel Hamed Mohamed ◽  
Marwa Shabban Elsayed
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Biofilm Formation ◽  
Chitosan Nanoparticles ◽  
Inhibitory Effect ◽  
Biofilm Inhibition ◽  
Expression Levels ◽  
The Mean ◽  
Biofilm Development

<abstract> <p>Antibiotic-resistant strains of <italic>Pseudomonas aeruginosa (P. aeruginosa</italic>) pose a major threat for healthcare-associated and community-acquired infections. <italic>P. aeruginosa</italic> is recognized as an opportunistic pathogen using quorum sensing (QS) system to regulate the expression of virulence factors and biofilm development. Thus, meddling with the QS system would give alternate methods of controlling the pathogenicity. This study aimed to assess the inhibitory impact of chitosan nanoparticles (CS-NPs) on <italic>P. aeruginosa</italic> virulence factors regulated by QS (e.g., motility and biofilm formation) and <italic>LasI</italic> and <italic>RhlI</italic> gene expression. Minimum inhibitory concentration (MIC) of CS-NPs against 30 isolates of <italic>P. aeruginosa</italic> was determined. The CS-NPs at sub-MIC were utilized to assess their inhibitory effect on motility, biofilm formation, and the expression levels of <italic>LasI</italic> and <italic>RhlI</italic> genes. CS-NPs remarkably inhibited the tested virulence factors as compared to the controls grown without the nanoparticles. The mean (±SD) diameter of swimming motility was decreased from 3.93 (±1.5) to 1.63 (±1.02) cm, and the mean of the swarming motility was reduced from 3.5 (±1.6) to 1.9 (±1.07) cm. All isolates became non-biofilm producers, and the mean percentage rate of biofilm inhibition was 84.95% (±6.18). Quantitative real-time PCR affirmed the opposition of QS activity by lowering the expression levels of <italic>LasI</italic> and <italic>RhlI</italic> genes; the expression level was decreased by 90- and 100-folds, respectively. In conclusion, the application of CS-NPs reduces the virulence factors significantly at both genotypic and phenotypic levels. These promising results can breathe hope in the fight against resistant <italic>P. aeruginosa</italic> by repressing its QS-regulated virulence factors.</p> </abstract>

scholarly journals A Novel Use of Allopurinol as A Quorum-Sensing Inhibitor in Pseudomonas aeruginosa

Antibiotics ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1385
Author(s):  
Ahmed Al Saqr ◽  
Mohammed F. Aldawsari ◽  
El-Sayed Khafagy ◽  
Moataz A. Shaldam ◽  
Wael A. H. Hegazy ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Virulence Factors ◽  
Virulence Factor ◽  
Cell Communication ◽  
Factor Production ◽  
In Silico Study ◽  
Liver And Kidney ◽  
Healthcare Associated ◽  
Virulence Factor Production

Pseudomonas aeruginosa can cause a variety of healthcare-associated infections by its arsenal of virulence factors. Virulence factor production is largely controlled by the cell-to-cell communication system termed quorum sensing (QS). Targeting QS may be a good approach to inhibit the production of virulence factors and attenuate pathogenicity without exerting selective stress on bacterial growth. This will greatly reduce the emergence of resistant mutants. In this work, we investigated the anti-virulence and anti-QS activities of the FDA-approved drug allopurinol against the P. aeruginosa PAO1 strain. Allopurinol at 200 µg/mL (1/10 MIC) significantly decreased the production of the QS-controlled Chromobacterium violaceum CV026 violet pigment violacein and other P. aeruginosa QS-controlled virulence factors phenotypically. Furthermore, allopurinol reduced the infiltration of P. aeruginosa and leucocytes and diminished the congestion in the liver and kidney tissues of infected mice. In silico study showed that allopurinol could compete with the autoinducers on binding to the receptors LasR and RhlR by hydrogen bonding. On the molecular level, qRT-PCR proved that allopurinol showed a significant downregulating effect on all tested QS-encoding genes that regulate virulence factor production. In summary, allopurinol is a promising QS inhibitor that may be useful in the future treatment of P. aeruginosa infection.

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