Cladodionen Is a Potential Quorum Sensing Inhibitor Against Pseudomonas aeruginosa

Wang, Mengjia; Zhao, Lu; Wu, Hao; Zhao, Chaoyue; Gong, Qianhong; Yu, Wengong

doi:10.3390/md18040205

Cited by 29 publications

(24 citation statements)

References 33 publications

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“…In addition, Ile 236 interacted to caryophyllene, trans-nerolidol, 2-(Isobutyryloxy)-Thymol methyl ether and β-elemene but not in cyperadiene. The difference in the interaction mode and affected amino acids present in the active site of PqsR is the reason for the difference in the docking energy of the bioactive compounds 35 . Interaction of the ligand to the active site deactivates the activity of PqsR by either making it inactive or preserving it as an unbound protein 36 .…”

Section: Resultsmentioning

confidence: 99%

In Silico Study of Ayapana Triplinervis Bioactive Compounds Against Quorum-Sensing System of Pseudomonas Aeruginosa

2021

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Quorum sensing (QS) is the way bacterial cells communicate can trigger or regulate pathogenicity in Pseudomonas aeruginosa. Targeting the quorum sensing system with the help of docking algorithms can reduce the cost and time to screen for potential anti-quorum sensing drugs. Ayapana triplinervis, an ethnobotanical from the Philippines is a potential source of bioactive compounds to inhibit quorum sensing. This study shows potential compounds present in Ayapana triplinervis that could disrupt the quorum sensing system in Pseudomonas aeruginosa with the use of molecular docking simulations. Selection and identification of bioactive compounds found in Ayapana triplinervis was based from previous metabolite screening reports. This study utilizes virtual screening in order to identify which among the compounds to be the potent quorum sensing inhibitor. The molecular structures of the thirty-one identified bioactive compounds were obtained from PubChem (nih.gov) in SDF file. These molecular structures of the compounds from Ayapana triplinervis served as the ligands and docked to the active site of the PqsR, PqsD, and LasR of the Pseudomonas aeruginosa using Autodock Vina algorithms. The bioactive compounds were virtually screened using Autodock Vina to determine the binding affinity of each compounds to the active site of PqsR, PqsD, and LasR. Compounds with a low binding affinity has a potential to be developed as anti-quorum agent to Pseudomonas aeruginosa. Results showed that out of the 31 compounds, caryophyllene, trans-nerolidol, 2-(Isobutyryloxy)-Thymol methyl ether, β-elemene, and cyperadiene have successfully inhibited the PqsR, PqsD, and LasR based from the computed binding affinity. 2- (Isobutyryloxy)-Thymol methyl ether formed hydrogen bond in the active site of all the proteins related governing the quorum sensing process of Pseudomonas aeruginosa, making the compound a candidate drug to disrupt the signaling pathway of the system.

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Section: Resultsmentioning

confidence: 99%

In Silico Study of Ayapana Triplinervis Bioactive Compounds Against Quorum-Sensing System of Pseudomonas Aeruginosa

2021

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“…Pseudomonas aeruginosa secretes a variety of virulence factors and forms biofilms, which are mainly regulated by the QS system (Wang et al, 2020 ), and PA2146 was found to be a gene related to the QS system. In our previous study, we found that PA2146 was more highly expressed in biofilms than in its planktonic counterpart after 8 and 16 h of incubation ( Figure 1A ).…”

Section: Resultsmentioning

confidence: 99%

“…The QS system is mainly regulated by four QS network sub-systems, including the las, rhl , PQS, and IQS systems. The hierarchical QS network plays a key role in the regulation of virulence gene expression (Wang et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

PA2146 Gene Knockout Is Associated With Pseudomonas aeruginosa Pathogenicity in Macrophage and Host Immune Response

She

Liu

Luo

et al. 2020

Front. Cell. Infect. Microbiol.

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Pseudomonas aeruginosa is a common gram-negative bacterium that usually causes nosocomial infection. The main pathogenicity of P. aeruginosa is caused by its virulence factors. PA2146 is reported to be a potential virulence-regulating gene and is highly expressed in the biofilms of P. aeruginosa . However, the effect of PA2146 mutant (PAO1Δ PA2146 ) on the macrophage immune response and murine models has not been reported. In the present study, PA2146 knockout was performed by homologous recombination. We found that PAO1Δ PA2146 stimulation significantly increased pyocyanin production but inhibited interleukin-6 secretion by neutrophils compared to PAO1 stimulation. In addition, PAO1Δ PA2146 treatment significantly inhibited cytokine production in macrophages independent of cell killing. In an acute pneumonia murine infection model, treatment with P. aeruginosa infected with PAO1Δ PA2146 inhibited cytokine secretion in the lungs but increased the infiltration of inflammatory cells compared to the wild-type group. The paradoxical results indicate that PA2146 deletion may also increase the production of virulence factors other than pyocyanin, which may not only increase inflammatory cell infiltration in the lungs but also lead to immune cells “shock.” Overall, our findings suggest that PA2146 could serve as a P. aeruginosa virulence-regulating gene that regulates its macrophage and host immune response.

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“…Much effort has been put into the inhibition of pigmented virulence factors such as staphyloxanthin and pyocyanin 71,72 but the approach is taken to their modulation is rather distinct. The first relies on the inhibition of druggable targets that are responsible for staphyloxanthin biosynthesis, 73,74 whereas the second is focussed on the modulation of quorum sensing mechanisms that lie upstream the biosynthetic pathway that builds up this virulence factor [75][76][77][78] . [83].…”

Section: Discussionmentioning

confidence: 99%

Synthesis and biological evaluation of thiazolidinedione derivatives with high ligand efficiency to P. aeruginosa PhzS

Froes

Chaves

Mendes

et al. 2021

Journal of Enzyme Inhibition and Medicinal Chemistry

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The thiazolidinone ring is found in compounds that have widespan biology activity and there is mechanism-based evidence that compounds bearing this moiety inhibit P. aeruginosa PhzS (PaPzhS), a key enzyme in the biosynthesis of the virulence factor named pyocyanin. Ten novel thiazolidinone derivatives were synthesised and screened against PaPhzS, using two orthogonal assays. The biological results provided by these and 28 other compounds, whose synthesis had been described, suggest that the dihydroquinazoline ring, found in the previous hit (A-Kd ¼ 18 mM and LE ¼ 0.20), is not required for PaPzhS inhibition, but unsubstituted nitrogen at the thiazolidinone ring is. The molecular simplification approach, pursued in this work, afforded an optimised lead compound (13-5-(2,4-dimethoxyphenyl)thiazolidine-2,4dione) with 10-fold improvement in affinity (Kd¼ 1.68 mM) and more than 100% increase in LE (0.45), which follows the same inhibition mode as the original hit compound (competitive to NADH).

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Cladodionen Is a Potential Quorum Sensing Inhibitor Against Pseudomonas aeruginosa

Cited by 29 publications

References 33 publications

In Silico Study of Ayapana Triplinervis Bioactive Compounds Against Quorum-Sensing System of Pseudomonas Aeruginosa

In Silico Study of Ayapana Triplinervis Bioactive Compounds Against Quorum-Sensing System of Pseudomonas Aeruginosa

PA2146 Gene Knockout Is Associated With Pseudomonas aeruginosa Pathogenicity in Macrophage and Host Immune Response

Synthesis and biological evaluation of thiazolidinedione derivatives with high ligand efficiency to P. aeruginosa PhzS

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