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.

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.

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 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 Candida albicans SET3 Plays a Role in Early Biofilm Formation, Interaction With Pseudomonas aeruginosa and Virulence in Caenorhabditis elegans

2021 ◽  
Vol 11 ◽  
Author(s):  
Ruan Fourie ◽  
Jacobus Albertyn ◽  
Olihile Sebolai ◽  
Onele Gcilitshana ◽  
Carolina H. Pohl
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Candida Albicans ◽  
Caenorhabditis Elegans ◽  
Biofilm Formation ◽  
Transcriptional Analysis ◽  
Infection Model ◽  
Environmental Cues ◽  
Interspecies Interaction

The yeast Candida albicans exhibits multiple morphologies dependent on environmental cues. Candida albicans biofilms are frequently polymicrobial, enabling interspecies interaction through proximity and contact. The interaction between C. albicans and the bacterium, Pseudomonas aeruginosa, is antagonistic in vitro, with P. aeruginosa repressing the yeast-to-hyphal switch in C. albicans. Previous transcriptional analysis of C. albicans in polymicrobial biofilms with P. aeruginosa revealed upregulation of genes involved in regulation of morphology and biofilm formation, including SET3, a component of the Set3/Hos2 histone deacetylase complex (Set3C). This prompted the question regarding the involvement of SET3 in the interaction between C. albicans and P. aeruginosa, both in vitro and in vivo. We found that SET3 may influence early biofilm formation by C. albicans and the interaction between C. albicans and P. aeruginosa. In addition, although deletion of SET3 did not alter the morphology of C. albicans in the presence of P. aeruginosa, it did cause a reduction in virulence in a Caenorhabditis elegans infection model, even in the presence of P. aeruginosa.

scholarly journals Baicalin Represses Type Three Secretion System of Pseudomonas aeruginosa through PQS System

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1497
Author(s):  
Pansong Zhang ◽  
Qiao Guo ◽  
Zhihua Wei ◽  
Qin Yang ◽  
Zisheng Guo ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Virulence Factors ◽  
Mammalian Cells ◽  
Secretion System ◽  
Chinese Herbs ◽  
Infection Model ◽  
Lung Pathology ◽  
Promising Alternative ◽  
The Impact

Therapeutics that target the virulence of pathogens rather than their viability offer a promising alternative for treating infectious diseases and circumventing antibiotic resistance. In this study, we searched for anti-virulence compounds against Pseudomonas aeruginosa from Chinese herbs and investigated baicalin from Scutellariae radix as such an active anti-virulence compound. The effect of baicalin on a range of important virulence factors in P. aeruginosa was assessed using luxCDABE-based reporters and by phenotypical assays. The molecular mechanism of the virulence inhibition by baicalin was investigated using genetic approaches. The impact of baicalin on P. aeruginosa pathogenicity was evaluated by both in vitro assays and in vivo animal models. The results show that baicalin diminished a plenty of important virulence factors in P. aeruginosa, including the Type III secretion system (T3SS). Baicalin treatment reduced the cellular toxicity of P. aeruginosa on the mammalian cells and attenuated in vivo pathogenicity in a Drosophila melanogaster infection model. In a rat pulmonary infection model, baicalin significantly reduced the severity of lung pathology and accelerated lung bacterial clearance. The PqsR of the Pseudomonas quinolone signal (PQS) system was found to be required for baicalin’s impact on T3SS. These findings indicate that baicalin is a promising therapeutic candidate for treating P. aeruginosa infections.

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 Impact of Pseudomonas aeruginosa quorum sensing on biofilm persistence in an in vivo intraperitoneal foreign-body infection model

Microbiology ◽  
2007 ◽  
Vol 153 (7) ◽  
pp. 2312-2320 ◽  
Author(s):  
Louise D Christensen ◽  
Claus Moser ◽  
Peter Ø Jensen ◽  
Thomas B Rasmussen ◽  
Lars Christophersen ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Foreign Body ◽  
Quorum Sensing ◽  
Infection Model
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