scholarly journals Potential of MurA Enzyme and GBAP in Fsr Quorum Sensing System as Antibacterial Drugs Target: In vitro and In silico Study of Antibacterial Compounds from Myrmecodia pendans

2020 ◽  
Vol 23 ◽  
Author(s):  
Eti Apriyanti ◽  
Mieke H. Satari ◽  
Dikdik Kurnia
Keyword(s):  
Quorum Sensing ◽  
Serine Protease ◽  
In Silico ◽  
Antibacterial Agent ◽  
Protein Inhibition ◽  
Chemical Structures ◽  
Sensing System ◽  
In Silico Study ◽  
Quorum Sensing System

Background: Increasing the resistance issue has become the reason for the development of new antibacterial in crucial condition. Many ways are tracked to determine the most effective antibacterial agent. Some proteins that are a key role in bacteria metabolism are targeted including MurA in cell wall biosynthesis and gelatinase biosynthesis-activating pheromone (GBAP) in Fsr Quorum Sensing (QS) system. Objective: The objective of this research is the analysis of compounds 1-4 from M. pendans as antibacterial and anti-QS activity trough protein inhibition by in silico study; focus on the structure-activity relationships, to appraise their role as an antibacterial and anti-QS agent in the molecular level. Method: Both activities of M. pendans compounds (1-4) were analyzed by in silico, comparing to Fosfomycin, Ambuic acid, Quercetin, and Taxifolin as a standard. Chemical structures of M. pendans compounds were converted using an online program molview. The compounds were docked to MurA, GBAP, gelatinase and serine protease using Autodock Vina in Pyrx 0.8 followed PYMOL to visualization and proteis.plus program to analyze of the complex. Results: All compounds from M. pendans bound on MurA, GBAP, gelatinase and serine protease except compound 2. This biflavonoid did not attach to MurA and serine protease yet is the favorable ligand for GBAP and gelatinase with the binding affinity of -6.9 and -9.4 Kcal/mol respectively. Meanwhile, for MurA and serine protease, compound 4 is the highest of bonding energy with values of -8.7 and -6.4 Kcal/mol before quercetin (MurA, -8.9 Kcal/mol) and taxifolin (serine protease, -6.6 Kcal/mol). Conclusion: Based on the data, biflavonoid acts better as anti-QS than an inhibitor of MurA enzyme while the others can be acted into both of them either therapeutic agent of anti-QS or antibacterial agent of MurA inhibitor.

scholarly journals Bio-Mechanism of Catechin as Pheromone Signal Inhibitor: Prediction of Antibacterial Agent Action Mode by In Vitro and In Silico Study

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6381
Author(s):  
Dikdik Kurnia ◽  
Zenika Febian Ramadhanty ◽  
Aprilina Mora Ardani ◽  
Achmad Zainuddin ◽  
Hendra Dian Adhita Dharsono ◽  
...  
Keyword(s):  
Antibiotic Resistance ◽  
Binding Energy ◽  
Serine Protease ◽  
In Silico ◽  
Antibacterial Agent ◽  
Antibacterial Agents ◽  
Chemical Structures ◽  
In Silico Study ◽  
And Control

The utilization of medicinal plants has long been explored for the discovery of antibacterial agents and the most effective mechanisms or new targets that can prevent and control the spread of antibiotic resistance. One kind of bacterial cell wall inhibition is the inactivation of the MurA enzyme that contributes to the formation of peptidoglycan. Another approach is to interfere with the cell–cell communication of bacteria called the Quorum sensing (QS) system. The blocking of auto-inducer such as gelatinase biosynthesis-activating pheromone (GBAP) can also suppress the virulence factors of gelatinase and serine protease. This research, in particular, aims to analyze lead compounds as antibacterial and anti-QS agents from Gambir (Uncaria gambir Roxburgh) through protein inhibition by in silico study. Antibacterial agents were isolated by bioactivity-guided isolation using a combination of chromatographic methods, and their chemical structures were determined by spectroscopic analysis methods. The in vitro antibacterial activity was evaluated by disc diffusion methods to determine inhibitory values. Meanwhile, in the in silico analysis, the compound of Uncaria gambir was used as ligand and compared with fosfomycin, ambuic acid, quercetin, and taxifolin as the standard ligand. These ligands were attached to MurA, GBAP, gelatinase, and serine proteases using Autodock Vina in PyRx 0.8 followed by PYMOL for combining the ligand conformation and proteins. plus programs to explore the complex, and visualized by Discovery Studio 2020 Client program. The antibacterial agent was identified as catechin that showed inhibitory activity against Enterococcus faecalis ATCC 29212 with inhibition zones of 11.70 mm at 10%, together with MIC and MBC values of 0.63 and 1.25 μg/mL, respectively. In the in silico study, the molecular interaction of catechin with MurA, GBAP, and gelatinase proteins showed good binding energy compared with two positive controls, namely fosfomycin and ambuic acid. It is better to use catechin–MurA (−8.5 Kcal/mol) and catechin–gelatinase (−7.8 Kcal/mol), as they have binding energies which are not marginally different from quercetin and taxifolin. On the other hand, the binding energy of serine protease is lower than quercetin, taxifolin, and ambuic acid. Based on the data, catechin has potency as an antibacterial through the inhibition of GBAP proteins, gelatinase, and serine protease that play a role in the QS system. This is the first discovery of the potential of catechin as an alternative antibacterial agent with an effective mechanism to prevent and control oral disease affected by antibiotic resistance.

scholarly journals Expression of a luxS Gene Is Not Required for Borrelia burgdorferi Infection of Mice via Needle Inoculation

2003 ◽  
Vol 71 (5) ◽  
pp. 2892-2896 ◽  
Author(s):  
Anette Hübner ◽  
Andrew T. Revel ◽  
Dena M. Nolen ◽  
Kayla E. Hagman ◽  
Michael V. Norgard
Keyword(s):  
Quorum Sensing ◽  
Borrelia Burgdorferi ◽  
Mammalian Host ◽  
Wild Type ◽  
Sensing System ◽  
Autoinducer 2 ◽  
Sensing Systems ◽  
Quorum Sensing System ◽  
Culture Supernatants

ABSTRACT The luxS gene product is an integral component of LuxS/autoinducer-2 (AI-2) quorum-sensing systems in bacteria. A putative luxS gene was expressed at comparable levels by Borrelia burgdorferi strain 297 cultivated either in vitro or in dialysis membrane chambers implanted in rat peritoneal cavities. Although the borrelial luxS gene functionally complemented a LuxS deficiency in Escherichia coli DH5α, AI-2-like activity could not be detected within B. burgdorferi culture supernatants or concentrated cell lysates. Finally, a luxS-deficient mutant of B. burgdorferi was infectious at wild-type levels when it was intradermally needle inoculated into mice, indicating that expression of luxS probably is not required for infectivity but, at the very least, is not essential for mammalian host adaptation. Our findings also challenge the notion that a LuxS/AI-2 quorum-sensing system is operative in B. burgdorferi.

scholarly journals Evaluation of the Antibacterial and Investigation of the Molecular Docking of New Derivatives of 1, 3, 4-Oxadiazole as Inhibitors of Quorum Sensing System in the Human Pathogen Pseudomonas Aeruginosa

2021 ◽  
Vol 8 (1) ◽  
pp. 27-33
Author(s):  
Sepideh Ghameshlouei ◽  
Nakisa Zarrabi Ahrabi ◽  
Ali Souldozi ◽  
Yasin SarveAhrabi
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Molecular Docking ◽  
Quorum Sensing ◽  
Regulatory Protein ◽  
Inhibitory Effect ◽  
Chemical Structures ◽  
Sensing System ◽  
Wide Range ◽  
Quorum Sensing System ◽  
Derivatives Of

Background: Oxadiazoles are a group of anti-inflammatory compounds that have a wide range of activity due to their higher efficacy. Pseudomonas aeruginosa is an opportunistic pathogen and a major pathogen of nosocomial infections. This study aimed to evaluate the antibacterial and investigation of the molecular docking of new derivatives of 1, 3, 4-oxadiazole against P. aeruginosa, in vitro & in silico. Materials and Methods: Four new derivatives were synthesized and added to our previous synthetic derivatives of 1, 3, 4-oxadiazole. The antibacterial activity of all derivatives was measured based on three standard species of P. aeruginosa using inhibition zone (IZ) and minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) methods. Then, employing the computational design of the drug by the molecular docking method, the inhibitory effect of synthetic compounds on the LasR regulatory protein of P. aeruginosa quorum sensing system was investigated, which plays an important role in regulating the expression of pathogenic genes in bacteria. Results: The chemical structures of new compounds were characterized by IR spectra and 1H-NMR. A variety of inhibitory effects were observed by the synthesized compounds – compound 4d and 4g, in particular. Also, the inhibitory effect of these two compounds on the LasR regulatory protein under the control of the quorum sensing system in P. aeruginosa was demonstrated by molecular docking. Conclusions: The results of this study showed that the two compounds containing the functional group of naphthalene and fluorophenyl have a significant effect on the inhibition of P. aeruginosa, as well as on the LasR protein of this bacterium.

scholarly journals Potential Allylpyrocatechol Derivatives as Antibacterial Agent Against Oral Pathogen of S. sanguinis ATCC 10,556 and as Inhibitor of MurA Enzymes: in vitro and in silico Study

2020 ◽  
Vol Volume 14 ◽  
pp. 2977-2985
Author(s):  
Dikdik Kurnia ◽  
Geofanny Sarah Hutabarat ◽  
Devi Windaryanti ◽  
Tati Herlina ◽  
Yetty Herdiyati ◽  
...  
Keyword(s):  
In Silico ◽  
Antibacterial Agent ◽  
Oral Pathogen ◽  
In Silico Study

scholarly journals Chemical probes for competitive profiling of the quorum sensing signal synthase PqsD of Pseudomonas aeruginosa

2016 ◽  
Vol 12 ◽  
pp. 2784-2792 ◽  
Author(s):  
Michaela Prothiwa ◽  
Dávid Szamosvári ◽  
Sandra Glasmacher ◽  
Thomas Böttcher
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Active Site ◽  
Chemical Probes ◽  
Active Site Cysteine ◽  
Sensing System ◽  
Highly Sensitive ◽  
Quorum Sensing System ◽  
Important Enzyme

The human pathogen Pseudomonas aeruginosa uses the pqs quorum sensing system to coordinate the production of its broad spectrum of virulence factors to facilitate colonization and infection of its host. Hereby, the enzyme PqsD is a virulence related quorum sensing signal synthase that catalyzes the central step in the biosynthesis of the Pseudomonas quinolone signals HHQ and PQS. We developed a library of cysteine reactive chemical probes with an alkyne handle for fluorescence tagging and report the selective and highly sensitive in vitro labelling of the active site cysteine of this important enzyme. Interestingly, only one type of probe, with a reactive α-chloroacetamide was capable of covalently reacting with the active site. We demonstrated the potential of our probes in a competitive labelling platform where we screened a library of synthetic HHQ and PQS analogues with heteroatom replacements and found several inhibitors of probe binding that may represent promising scaffolds for the development of customized PqsD inhibitors as well as a chemical toolbox to investigate the activity and active site specificity of the enzyme.

scholarly journals Escherichia coliO157:H7 Lacking theqseBC-Encoded Quorum-Sensing System Outcompetes the Parental Strain in Colonization of Cattle Intestines

2014 ◽  
Vol 80 (6) ◽  
pp. 1882-1892 ◽  
Author(s):  
V. K. Sharma ◽  
T. A. Casey
Keyword(s):  
Quorum Sensing ◽  
Parental Strain ◽  
Response Regulator ◽  
Stress Hormones ◽  
Gene Encoding ◽  
Fecal Shedding ◽  
Sensing System ◽  
Quorum Sensing System ◽  
Parental Level

ABSTRACTTheqseBC-encoded quorum-sensing system regulates the motility ofEscherichia coliO157:H7 in response to bacterial autoinducer 3 (AI-3) and the mammalian stress hormones epinephrine (E) and norepinephrine (NE). TheqseCgene encodes a sensory kinase that autophosphorylates in response to AI-3, E, or NE and subsequently phosphorylates its cognate response regulator QseB. In the absence of QseC, QseB downregulates bacterial motility and virulence in animal models. In this study, we found that 8- to 10-month-old calves orally inoculated with a mixture ofE. coliO157:H7 and its isogenicqseBCmutant showed significantly higher fecal shedding of theqseBCmutant.In vitroanalysis revealed similar growth profiles and motilities of theqseBCmutant and the parental strain in the presence or absence of NE. The magnitudes of the response to NE and expression of flagellar genesflhDandfliCwere also similar for theqseBCmutant and the parental strain. The expression ofler(a positive regulator of the locus of enterocyte effacement [LEE]), theler-regulatedespAgene, and thecsgAgene (encoding curli fimbriae) was increased in theqseBCmutant compared to the parental strain. On the other hand, growth, motility, and transcription offlhD,fliC,ler,espA, andcsgAwere significantly reduced in theqseBCmutant complemented with a plasmid-cloned copy of theqseBCgenes. Thus,in vitromotility and gene expression data indicate that the near-parental level of motility, ability to respond to NE, and enhanced expression of LEE and curli genes might in part be responsible for increased colonization and fecal shedding of theqseBCmutant in calves.

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