WITHDRAWN: Quorum sensing inhibitory agents: Recent approaches towards the new antimicrobial agents from natural sources

Most of the infections caused by multi-drug resistant (MDR) P. aeruginosa strains are extremely difficult to be treated with conventional antibiotics. Biofilm formation and efflux pumps are recognized as the major antibiotic resistance mechanisms in MDR P. aeruginosa. Biofilm formation by P. aeruginosa depends mainly on the cell-to-cell communication quorum-sensing (QS) systems. Titanium dioxide nanoparticles (TDN) have been used as antimicrobial agents against several microorganisms but have not been reported as an anti-QS agent. This study aims to evaluate the impact of titanium dioxide nanoparticles (TDN) on QS and efflux pump genes expression in MDR P. aeruginosa isolates. The antimicrobial susceptibility of 25 P. aeruginosa isolates were performed by Kirby–Bauer disc diffusion. Titanium dioxide nanoparticles (TDN) were prepared by the sol gel method and characterized by different techniques (DLS, HR-TEM, XRD, and FTIR). The expression of efflux pumps in the MDR isolates was detected by the determination of MICs of different antibiotics in the presence and absence of carbonyl cyanide m-chlorophenylhydrazone (CCCP). Biofilm formation and the antibiofilm activity of TDN were determined using the tissue culture plate method. The effects of TDN on the expression of QS genes and efflux pump genes were tested using real-time polymerase chain reaction (RT-PCR). The average size of the TDNs was 64.77 nm. It was found that TDN showed a significant reduction in biofilm formation (96%) and represented superior antibacterial activity against P. aeruginosa strains in comparison to titanium dioxide powder. In addition, the use of TDN alone or in combination with antibiotics resulted in significant downregulation of the efflux pump genes (MexY, MexB, MexA) and QS-regulated genes (lasR, lasI, rhll, rhlR, pqsA, pqsR) in comparison to the untreated isolate. TDN can increase the therapeutic efficacy of traditional antibiotics by affecting efflux pump expression and quorum-sensing genes controlling biofilm production.

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Effect of Essential Oils on the Inhibition of Biofilm and Quorum Sensing in Salmonella Enteritidis 13076 and Salmonella Typhimurium 14028

Antibiotics ◽

10.3390/antibiotics10101191 ◽

2021 ◽

Vol 10 (10) ◽

pp. 1191

Author(s):

Yuliany Guillín ◽

Marlon Cáceres ◽

Rodrigo Torres ◽

Elena Stashenko ◽

Claudia Ortiz

Keyword(s):

Quorum Sensing ◽

Essential Oils ◽

Salmonella Enterica ◽

Salmonella Enteritidis ◽

Antimicrobial Agents ◽

Multidrug Resistant ◽

Transcriptional Analysis ◽

Bacterial Cells ◽

Sem Images ◽

Biofilm Inhibition

The emergence of multidrug-resistant microorganisms represents a global challenge that has led to a search for new antimicrobial compounds. Essential oils (EOs) from medicinal aromatic plants are a potential alternative for conventional antibiotics. In this study, the antimicrobial and anti-biofilm potential of 15 EOs was evaluated on planktonic and biofilm-associated cells of Salmonella enterica serovar Enteritidis ATCC 13076 (S. enteritidis) and Salmonella enterica serovar Typhimurium ATCC 14028 (S. typhimurium). In total, 4 out of 15 EOs showed antimicrobial activity and 6 EOs showed anti-biofilm activity against both strains. The EO from the Lippia origanoides chemotype thymol-carvacrol II (LTC II) presented the lowest minimum inhibitory concentration (MIC50 = 0.37 mg mL−1) and minimum bactericidal concentration (MBC = 0.75 mg mL−1) values. This EO also presented the highest percentage of biofilm inhibition (>65%) on both microorganisms, which could be confirmed by scanning electron microscopy (SEM) images. Transcriptional analysis showed significant changes in the expression of the genes related to quorum sensing and the formation of the biofilm. EOs could inhibit the expression of genes involved in the quorum sensing mechanism (luxR, luxS, qseB, sdiA) and biofilm formation (csgA, csgB, csgD, flhD, fliZ, and motB), indicating their potential use as anti-biofilm antimicrobial agents. However, further studies are needed to elucidate the action mechanisms of essential oils on the bacterial cells under study.

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Peptide Mix from Olivancillaria hiatula Interferes with Cell-to-Cell Communication in Pseudomonas aeruginosa

BioMed Research International ◽

10.1155/2019/5313918 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12

Author(s):

Edward Ntim Gasu ◽

Hubert Senanu Ahor ◽

Lawrence Sheringham Borquaye

Keyword(s):

Pseudomonas Aeruginosa ◽

Quorum Sensing ◽

Biofilm Formation ◽

Antimicrobial Agents ◽

Cell Communication ◽

Microtiter Plate ◽

Antibiofilm Activity ◽

Dependent Manner ◽

Biofilm Inhibition ◽

Swarming Motility

Bacteria in biofilms are encased in an extracellular polymeric matrix that limits exposure of microbial cells to lethal doses of antimicrobial agents, leading to resistance. In Pseudomonas aeruginosa, biofilm formation is regulated by cell-to-cell communication, called quorum sensing. Quorum sensing facilitates a variety of bacterial physiological functions such as swarming motility and protease, pyoverdine, and pyocyanin productions. Peptide mix from the marine mollusc, Olivancillaria hiatula, has been studied for its antibiofilm activity against Pseudomonas aeruginosa. Microscopy and microtiter plate-based assays were used to evaluate biofilm inhibitory activities. Effect of the peptide mix on quorum sensing-mediated processes was also evaluated. Peptide mix proved to be a good antibiofilm agent, requiring less than 39 μg/mL to inhibit 50% biofilm formation. Micrographs obtained confirmed biofilm inhibition at 1/2 MIC whereas 2.5 mg/mL was required to degrade preformed biofilm. There was a marked attenuation in quorum sensing-mediated phenotypes as well. At 1/2 MIC of peptide, the expression of pyocyanin, pyoverdine, and protease was inhibited by 60%, 72%, and 54%, respectively. Additionally, swarming motility was repressed by peptide in a dose-dependent manner. These results suggest that the peptide mix from Olivancillaria hiatula probably inhibits biofilm formation by interfering with cell-to-cell communication in Pseudomonas aeruginosa.

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Plant Phenolics and Phenolic-Enriched Extracts as Antimicrobial Agents against Food-Contaminating Microorganisms

Antioxidants ◽

10.3390/antiox9020165 ◽

2020 ◽

Vol 9 (2) ◽

pp. 165 ◽

Cited By ~ 14

Author(s):

Miklós Takó ◽

Erika Beáta Kerekes ◽

Carolina Zambrano ◽

Alexandra Kotogán ◽

Tamás Papp ◽

...

Keyword(s):

Quorum Sensing ◽

Antimicrobial Agents ◽

Antimicrobial Properties ◽

Toxin Production ◽

Plant Phenolics ◽

Food Preservatives ◽

Plant Materials ◽

Bioactive Properties ◽

Spoilage Bacteria ◽

Phenolic Extracts

Phenolic compounds and extracts with bioactive properties can be obtained from many kinds of plant materials. These natural substances have gained attention in the food research as possible growth inhibitors of foodborne pathogenic and spoilage bacteria. Many phenolic-enriched plant extracts and individual phenolics have promising anti-quorum sensing potential as well and can suppress the biofilm formation and toxin production of food-related pathogens. Various studies have shown that plant phenolics can substitute or support the activity of synthetic food preservatives and disinfectants, which, by the way, can provoke serious concerns in consumers. In this review, we will provide a brief insight into the bioactive properties, i.e., the antimicrobial, anti-quorum sensing, anti-biofilm and anti-enterotoxin activities, of plant phenolic extracts and compounds, with special attention to pathogen microorganisms that have food relation. Carbohydrase aided applications to improve the antimicrobial properties of phenolic extracts are also discussed.

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Antimicrobial and anti-Quorum Sensing activities of selected medicinal plants of Ethiopia: Implication for development of potent antimicrobial agents

BMC Microbiology ◽

10.1186/s12866-016-0765-9 ◽

2016 ◽

Vol 16 (1) ◽

Cited By ~ 31

Author(s):

Ketema Bacha ◽

Yinebeb Tariku ◽

Fisseha Gebreyesus ◽

Shibru Zerihun ◽

Ali Mohammed ◽

...

Keyword(s):

Quorum Sensing ◽

Medicinal Plants ◽

Antimicrobial Agents

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Co-existence of LasI, RhI, and Pseudomonas Quinolone Signal Quorum-sensing Genes in Clinical Pseudomonas aeruginosa Isolates

International Journal of Drug Delivery Technology ◽

10.25258/ijddt.10.3.5 ◽

2020 ◽

Vol 10 (03) ◽

pp. 337-343

Author(s):

Anwer J. Faisal ◽

Munim Radwan Ali ◽

Layla Abdulhamid Said

Keyword(s):

Pseudomonas Aeruginosa ◽

Quorum Sensing ◽

Antimicrobial Agents ◽

Multidrug Resistant ◽

Antibiotics Resistance ◽

Bacterial Isolates ◽

Antimicrobial Drugs ◽

Physiological Processes ◽

Pseudomonas Quinolone Signal ◽

Production Pattern

Pseudomonas aeruginosa can regulate different group actives and physiological processes through the quorum sensing mechanism. The aims of this research were to detect the presence of quorum sensing genes in 50 clinical P. aeruginosa isolates, which represent by (lasI, lasR, rhlI, and rhlR) and Pseudomonas quinolone signal (PQS) (PgsA, PgsB, PgsC, PgsD, PgsE, and MvfR) genes by Polymerase chain reaction (PCR) technique and interaction between the two systems. Isolates were subjected to test their susceptibility to 12 antimicrobial drugs, 64% of isolates showed resistance to ceftazidime, followed by carbencillin (56%), while only 8% were resistant to imipenem. In addition, all of the bacterial isolates were distributed within three multidrug-resistant (MDR) patterns, viz., A, B, and C. The highest rate of MDR was showed with MDR pattern C, in which bacterial isolates showed resistance to resist (9→11) antimicrobial drugs. Results revealed that P. aeruginosa isolates have different gene patterns, viz., A to E. According to quorum sensing genes production, pattern A found to express all the genes in LasI, RhI, and PQS system, while pattern B has a defective for the production of lasR, rhlR genes, while the same isolates have the PQS system all present. Significantly, there is a positive relationship between las and rhl system and regulation of antibiotics resistance, in which the bacterial isolates that have las and rhl genes showed high resistance to common antimicrobial agents under study. These findings suggest that PQS can function as an intercellular signal in P. aeruginosa that is not restricted only to alkyl homoserine lactones (AHL).

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A Comprehensive Appraisal of Chalcones and Their Heterocyclic Analogs as Antimicrobial Agents

Current Organic Chemistry ◽

10.2174/1385272824999200922090524 ◽

2020 ◽

Vol 24 (23) ◽

pp. 2755-2781

Author(s):

Riddhi Salotra ◽

Divya Utreja

Keyword(s):

Antimicrobial Agents ◽

Biological Activities ◽

Structural Diversity ◽

Natural Sources ◽

Anti Cancer ◽

Heterocyclic Derivatives ◽

Synthetic Methodologies ◽

Microbial Potential ◽

High Degree ◽

Therapeutic Profile

Owing to the growing demand for compelling antimicrobial agents, chalcones and their heterocyclic derivatives have engrossed prodigious attention of medicinal chemists as an effective clinical template for the synthesis of such agents on account of their structural diversity and molecular flexibility. Chalcones are considered as a fortunate scaffold in the field of both synthetic as well as natural product chemistry. They are reflected as a remarkable section of logically occurring pharmacophores that possess a comprehensive scale of biological activities, such as anti-cancer, anti-malarial, anti-viral and anti-inflammatory, rendering them with a high degree of assortment and noble therapeutic profile. They act as a crucial intermediate for the synthesis of novel heterocyclic skeletons holding biodynamic behavior. This review emphasizes on different aspects of chalcones including their natural sources, recent synthetic methodologies and evaluation of their anti-microbial potential. It is expected as a persuasive compilation on chalcones that may benefit the experts to design potent and less toxic chalcone referents as medicinal agents.

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Quorum Sensing Regulation as a Target for Antimicrobial Therapy

Mini-Reviews in Medicinal Chemistry ◽

10.2174/1389557521666211202115259 ◽

2021 ◽

Vol 21 ◽

Author(s):

Caterine Henríquez Ruiz ◽

Estefanie Osorio-Llanes ◽

Mayra Hernández Trespalacios ◽

Evelyn Mendoza-Torres ◽

Wendy Rosales ◽

...

Keyword(s):

Quorum Sensing ◽

Molecular Mechanisms ◽

Bacterial Resistance ◽

Antimicrobial Agents ◽

Bacterial Species ◽

Cell Communication ◽

Structural Evolution ◽

Structural Diversity ◽

Signal Molecules ◽

Bacterial Survival

: Some bacterial species use a cell-to-cell communication mechanism called Quorum Sensing (QS). Bacteria release small diffusible molecules, usually termed signals which allow the activation of beneficial phenotypes that guarantee bacterial survival and the expression of a diversity of virulence genes in response to an increase in population density. The study of the molecular mechanisms that relate signal molecules with bacterial pathogenesis is an area of growing interest due to its use as a possible therapeutic alternative through the development of synthetic analogues of autoinducers as a strategy to regulate bacterial communication as well as the study of bacterial resistance phenomena, the study of these relationships is based on the structural diversity of natural or synthetic autoinducers and their ability to inhibit bacterial QS, which can be approached with a molecular perspective from the following topics: i) Molecular signals and their role in QS regulation; ii) Strategies in the modulation of Quorum Sensing; iii) Analysis of Bacterial QS circuit regulation strategies; iv) Structural evolution of natural and synthetic autoinducers as QS regulators. This mini-review allows a molecular view of the QS systems, showing a perspective on the importance of the molecular diversity of autoinducer analogs as a strategy for the design of new antimicrobial agents.

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Nanocellulose in Drug Delivery and Antimicrobially Active Materials

Polymers ◽

10.3390/polym12122825 ◽

2020 ◽

Vol 12 (12) ◽

pp. 2825

Author(s):

Kaja Kupnik ◽

Mateja Primožič ◽

Vanja Kokol ◽

Maja Leitgeb

Keyword(s):

Drug Delivery ◽

Antimicrobial Activity ◽

Sustained Release ◽

Drug Delivery Systems ◽

Antimicrobial Agents ◽

Metal Oxide Nanoparticles ◽

Biological Properties ◽

Oxide Nanoparticles ◽

Active Materials ◽

Natural Sources

In recent years, nanocellulose (NC) has also attracted a great deal of attention in drug delivery systems due to its unique physical properties, specific surface area, low risk of cytotoxicity, and excellent biological properties. This review is focused on nanocellulose based systems acting as carriers to be used in drug or antimicrobial delivery by providing different but controlled and sustained release of drugs or antimicrobial agents, respectively, thus showing potential for different routes of applications and administration. Microorganisms are increasingly resistant to antibiotics, and because, generally, the used metal or metal oxide nanoparticles at some concentration have toxic effects, more research has focused on finding biocompatible antimicrobial agents that have been obtained from natural sources. Our review contains the latest research from the last five years that tested nanocellulose-based materials in the field of drug delivery and antimicrobial activity.

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Indole-based novel small molecules for the modulation of bacterial signalling pathways

Organic & Biomolecular Chemistry ◽

10.1039/c4ob02096k ◽

2015 ◽

Vol 13 (3) ◽

pp. 925-937 ◽

Cited By ~ 31

Author(s):

Nripendra Nath Biswas ◽

Samuel K. Kutty ◽

Nicolas Barraud ◽

George M. Iskander ◽

Renate Griffith ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Quorum Sensing ◽

Small Molecules ◽

Antimicrobial Agents ◽

Homoserine Lactone ◽

Signalling Pathways ◽

Gram Negative Bacteria ◽

Gram Negative

Indole basedN-acylatedl-homoserine lactone (AHL) mimics were developed as quorum sensing (QS) inhibitors for Gram-negative bacteriaPseudomonas aeruginosaand can be used as novel antimicrobial agents.

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