Growth-phase specific regulation of cviI/R based quorum sensing associated virulence factors in Chromobacterium violaceum by linalool, a monoterpenoid

The cell density-dependent mechanism, quorum sensing (QS), regulates the expression of virulence factors. Its inhibition has been proposed as a promising new strategy to prevent bacterial pathogenicity. In this study, 827 strains from the microbiota of sea anemones and holothurians were screened for their ability to produce quorum-sensing inhibitor (QSI) compounds. The strain M3-10, identified as Vibrio alginolyticus by 16S rRNA gene sequencing, as well as ANIb and dDDH analyses, was selected for its high QSI activity. Bioassay-guided fractionation of the cell pellet extract from a fermentation broth of strain M3-10, followed by LC–MS and NMR analyses, revealed tyramine and N-acetyltyramine as the active compounds. The QS inhibitory activity of these molecules, which was confirmed using pure commercially available standards, was found to significantly inhibit Chromobacterium violaceum ATCC 12472 violacein production and virulence factors, such as pyoverdine production, as well as swarming and twitching motilities, produced by Pseudomonas aeruginosa PAO1. This constitutes the first study to screen QSI-producing strains in the microbiota of anemones and holothurians and provides an insight into the use of naturally produced QSI as a possible strategy to combat bacterial infections.

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Amphypterygium adstringens Anacardic Acid Mixture Inhibits Quorum Sensing-controlled Virulence Factors of Chromobacterium violaceum and Pseudomonas aeruginosa

Archives of Medical Research ◽

10.1016/j.arcmed.2013.10.004 ◽

2013 ◽

Vol 44 (7) ◽

pp. 488-494 ◽

Cited By ~ 28

Author(s):

Israel Castillo-Juárez ◽

Rodolfo García-Contreras ◽

Norma Velázquez-Guadarrama ◽

Marcos Soto-Hernández ◽

Mariano Martínez-Vázquez

Keyword(s):

Pseudomonas Aeruginosa ◽

Quorum Sensing ◽

Virulence Factors ◽

Chromobacterium Violaceum ◽

Anacardic Acid ◽

Acid Mixture

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Effect of Bromination on the Quorum Sensing-Inhibiting Properties of Indole-3-Carboxaldehydes in Chromobacterium violaceum AHL System

Microbiology Research ◽

10.3390/microbiolres12020025 ◽

2021 ◽

Vol 12 (2) ◽

pp. 376-382

Author(s):

Chesley A. Kemp ◽

Donna K. McCullough ◽

Dobrusia Bialonska ◽

Paul J. T. Johnson

Keyword(s):

Escherichia Coli ◽

Quorum Sensing ◽

Virulence Factors ◽

Indole Derivative ◽

Chromobacterium Violaceum ◽

Quorum Sensing Inhibition ◽

Signaling Molecule ◽

Bacterial Communication ◽

Ic50 Value ◽

Ic50 Values

Quorum sensing (QS) is a form of bacterial communication involved in the production of virulence factors in many species. As a result, inhibition of quorum sensing may be of use in mitigating pathogenesis. The signaling molecule indole is currently being investigated as a target for quorum sensing inhibition (QSI) and the indole derivative indole-3-carboxaldehyde (ICA) has been shown to inhibit quorum sensing-mediated behaviors in Escherichia coli. In this study, we investigate bromination as a method of increasing the QSI capabilities of indole carboxaldehydes. The IC50 values of three monobrominated indole carboxaldehydes (5-bromoindole-3-carboxaldehyde, 6-bromoindole-3-carboxaldehyde, and 7-bromoindole-3-carboxaldehyde) were determined and compared to the IC50 value of ICA. The bromination of these indole carboxaldehydes reduced the IC50 values between 2- and 13-fold, indicating that bromination significantly increases the potency of these indole carboxaldehydes.

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

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i24b31443 ◽

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.

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Quorum Sensing – A Stratagem for Conquering Multi-Drug Resistant Pathogens

Current Pharmaceutical Design ◽

10.2174/1381612826666201210105638 ◽

2020 ◽

Vol 26 ◽

Author(s):

Madison Tonkin ◽

Shama Khan ◽

Mohmmad Younus Wani ◽

Aijaz Ahmad

Keyword(s):

Drug Resistance ◽

Quorum Sensing ◽

Virulence Factors ◽

Biofilm Formation ◽

Cell Communication ◽

Natural Compounds ◽

Quorum Sensing Inhibitors ◽

Communication Technique ◽

Multicellular Organisms ◽

Chemical Strategies

: Quorum sensing is defined as cell to cell communication between microorganisms, which enables microorganisms to behave as multicellular organisms. Quorum sensing enables many collaborative benefits such as synchronisation of virulence factors and biofilm formation. Both quorum sensing as well as biofilm formation encourage the development of drug resistance in microorganisms. Biofilm formation and quorum sensing are causally linked to each other and play role in the pathogenesis of microorganisms. With the increasing drug resistance against the available antibiotics and antifungal medications, scientists are combining different options to develop new strategies. Such strategies rely on the inhibition of the communication and virulence factors rather than on killing or inhibiting the growth of the microorganisms. This review encompasses the communication technique used by microorganisms, how microorganism resistance is linked to quorum sensing and various chemical strategies to combat quorum sensing and thereby drug resistance. Several compounds have been identified as quorum sensing inhibitors and are known to be effective in reducing resistance as they do not kill the pathogens but rather disrupt their communication. Natural compounds have been identified as anti-quorum sensing agents. However, natural compounds present several related disadvantages. Therefore, the need for the development of synthetic or semi-synthetic compounds has arisen. This review argues that anti-quorum sensing compounds are effective in disrupting quorum sensing and could therefore be effective in reducing microorganism drug resistance.

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Pseudomonas aeruginosa PA80 is a cystic fibrosis isolate deficient in RhlRI quorum sensing

Scientific Reports ◽

10.1038/s41598-021-85100-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Syed A. K. Shifat Ahmed ◽

Michelle Rudden ◽

Sabrina M. Elias ◽

Thomas J. Smyth ◽

Roger Marchant ◽

...

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Quorum Sensing ◽

Virulence Factors ◽

Genomic Islands ◽

Clinical Strain ◽

Whole Genome ◽

Synonymous Mutations ◽

Wide Range

AbstractPseudomonas aeruginosa uses quorum sensing (QS) to modulate the expression of several virulence factors that enable it to establish severe infections. The QS system in P. aeruginosa is complex, intricate and is dominated by two main N-acyl-homoserine lactone circuits, LasRI and RhlRI. These two QS systems work in a hierarchical fashion with LasRI at the top, directly regulating RhlRI. Together these QS circuits regulate several virulence associated genes, metabolites, and enzymes in P. aeruginosa. Paradoxically, LasR mutants are frequently isolated from chronic P. aeruginosa infections, typically among cystic fibrosis (CF) patients. This suggests P. aeruginosa can undergo significant evolutionary pathoadaptation to persist in long term chronic infections. In contrast, mutations in the RhlRI system are less common. Here, we have isolated a clinical strain of P. aeruginosa from a CF patient that has deleted the transcriptional regulator RhlR entirely. Whole genome sequencing shows the rhlR locus is deleted in PA80 alongside a few non-synonymous mutations in virulence factors including protease lasA and rhamnolipid rhlA, rhlB, rhlC. Importantly we did not observe any mutations in the LasRI QS system. PA80 does not appear to have an accumulation of mutations typically associated with several hallmark pathoadaptive genes (i.e., mexT, mucA, algR, rpoN, exsS, ampR). Whole genome comparisons show that P. aeruginosa strain PA80 is closely related to the hypervirulent Liverpool epidemic strain (LES) LESB58. PA80 also contains several genomic islands (GI’s) encoding virulence and/or resistance determinants homologous to LESB58. To further understand the effect of these mutations in PA80 QS regulatory and virulence associated genes, we compared transcriptional expression of genes and phenotypic effects with isogenic mutants in the genetic reference strain PAO1. In PAO1, we show that deletion of rhlR has a much more significant impact on the expression of a wide range of virulence associated factors rather than deletion of lasR. In PA80, no QS regulatory genes were expressed, which we attribute to the inactivation of the RhlRI QS system by deletion of rhlR and mutation of rhlI. This study demonstrates that inactivation of the LasRI system does not impact RhlRI regulated virulence factors. PA80 has bypassed the common pathoadaptive mutations observed in LasR by targeting the RhlRI system. This suggests that RhlRI is a significant target for the long-term persistence of P. aeruginosa in chronic CF patients. This raises important questions in targeting QS systems for therapeutic interventions.

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