Article
Microbiology
Wen-Ru Li, Tao-Hua Zeng, Zhi-Qing Zhang, Qing-Shan Shi, Xiao-Bao Xie
Summary: In this study, it was found that geraniol can inhibit the growth of Pseudomonas aeruginosa, prolong the lag phase and growth period. Geraniol also suppresses the expression of the three quorum sensing systems of P. aeruginosa, thereby attenuating the virulence factors regulated by these systems. This research is significant for improving the treatment of bacterial infections caused by P. aeruginosa.
FRONTIERS IN MICROBIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Shen Mao, Qiaoqiang Li, Zhikun Yang, Yasheng Li, Xinyi Ye, Hong Wang
Summary: In this paper, six series of benzoheterocyclic sulfoxide derivatives were designed and synthesised as Pseudomonas aeruginosa quorum sensing inhibitors. The experimental results showed that 6b significantly inhibited the formation of P. aeruginosa PAO1 biofilm without affecting the growth. Further mechanistic studies revealed that 6b mainly acted as a quorum sensing inhibitor through the las system. Silico molecular docking studies demonstrated the molecular binding between 6b and the P. aeruginosa quorum sensing receptor LasR via hydrogen bonding interactions. The structure-activity relationship and docking studies suggested the potential of 6b as anti-biofilm compounds for further studies on microbial resistance.
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2023)
Article
Microbiology
Dan Yang, Suqi Hao, Ling Zhao, Fei Shi, Gang Ye, Yuanfeng Zou, Xu Song, Lixia Li, Zhongqiong Yin, Xiaoli He, Shiling Feng, Helin Chen, Yu Zhang, Yuanze Gao, Yinglun Li, Huaqiao Tang
Summary: The study found that paeonol has good anti-biofilm activity against Gram-negative bacteria and anti-QS activity, effectively reducing the virulence of P. aeruginosa. In vivo studies showed that paeonol could reduce the pathogenicity of P. aeruginosa and enhance the survival rate of C. elegans.
FRONTIERS IN MICROBIOLOGY
(2021)
Article
Plant Sciences
Muzamil Ahmad Rather, Kuldeep Gupta, Manabendra Mandal
Summary: The study evaluated the inhibitory effect of methanol extract of Cuphea carthagenensis on biofilm and quorum sensing (QS) activity in Pseudomonas aeruginosa, demonstrating a significant suppression of biofilm formation and virulence factors.
JOURNAL OF ETHNOPHARMACOLOGY
(2021)
Article
Infectious Diseases
Nosipho Wendy S'thebe, Jamiu Olaseni Aribisala, Saheed Sabiu
Summary: Essential oils from two sunflower cultivars (AGSUN 5102 CLP and AGSUN 5106 CLP) were found to have significant antipathogenic effects against Pseudomonas aeruginosa, making them potential candidates for novel therapeutic alternatives.
Article
Immunology
Giulia Giallonardi, Morgana Letizia, Marta Mellini, Emanuela Frangipani, Nigel Halliday, Stephan Heeb, Miguel Camara, Paolo Visca, Francesco Imperi, Livia Leoni, Paul Williams, Giordano Rampioni
Summary: Pseudomonas aeruginosa is a model pathogen with multiple quorum sensing circuits that control virulence factor production and biofilm formation. The pqs QS system in P. aeruginosa synthesizes AQs including HHQ and PQS, which act as signal molecules. Transcriptomic analyses show that HHQ and PQS influence gene expression through PqsR-dependent and -independent pathways. However, HQNO has no effect on P. aeruginosa transcriptome. Mutation of pqsL in P. aeruginosa leads to autolysis in colony biofilms through the accumulation of HHQ and activation of Pf4 prophage.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Chemistry, Multidisciplinary
Christian Schuetz, Duy-Khiet Ho, Mostafa Mohamed Hamed, Ahmed Saad Abdelsamie, Teresa Roehrig, Christian Herr, Andreas Martin Kany, Katharina Rox, Stefan Schmelz, Lorenz Siebenbuerger, Marius Wirth, Carsten Boerger, Samir Yahiaoui, Robert Bals, Andrea Scrima, Wulf Blankenfeldt, Justus Constantin Horstmann, Rebekka Christmann, Xabier Murgia, Marcus Koch, Aylin Berwanger, Brigitta Loretz, Anna Katharina Herta Hirsch, Rolf Wolfgang Hartmann, Claus-Michael Lehr, Martin Empting
Summary: A new generation of quorum sensing inhibitors (QSI) is reported to effectively inhibit the virulence of Pseudomonas aeruginosa and enhance antibiotic efficacy, potentially preventing the development of antimicrobial resistance. Additionally, a significant synergistic effect of QSI in combination with tobramycin against P. aeruginosa biofilms is demonstrated, showing promising implications for adjunctive pathoblocker-mediated therapy.
Article
Chemistry, Medicinal
Yinglu Wang, Qian Zheng, Li Li, Lile Pan, Hu Zhu
Summary: Quorum sensing (QS) plays an important role in regulating the pathogenicity of bacteria, and cyclo (L-Trp-L-Ser) and its derivatives have been found to exhibit anti-QS activity, making them potential candidates for developing anti-virulence agents.
Article
Biochemistry & Molecular Biology
Megha Shah, Veronique L. Taylor, Diane Bona, Yvonne Tsao, Sabrina Y. Stanley, Sheila M. Pimentel-Elardo, Matthew McCallum, Joseph Bondy-Denomy, P. Lynne Howell, Justin R. Nodwell, Alan R. Davidson, Trevor F. Moraes, Karen L. Maxwell
Summary: The study identified a new phage anti-activator protein, Aqs1, which inhibits phage infection by suppressing the quorum-sensing master regulator LasR. Aqs1 also inhibits the bacterial type IV pilus assembly ATPase protein PilB, preventing phages from superinfecting host cells. This research highlights the potential of small phage proteins to disrupt key biological pathways and offers insights into the evolutionary dynamics between phages and their hosts.
Article
Biochemistry & Molecular Biology
Zsofia Berkl, Ildiko Fekete-Kertesz, Kata Buda, Emese Vaszita, Eva Fenyvesi, Lajos Szente, Monika Molnar
Summary: Quorum sensing (QS) is a communication process in microorganisms that coordinates their activities through producing and detecting low-molecular-weight signal molecules. Cyclodextrins (CDs) can reduce signal communication and inhibit biofilm formation in pathogenic bacteria. The size, structure, and concentration of CDs are identified as key factors influencing biofilm formation. Alpha-CD and its random methylated and polymer derivatives demonstrate outstanding inhibitory efficiency.
Review
Chemistry, Medicinal
Qiaoqiang Li, Shen Mao, Hong Wang, Xinyi Ye
Summary: The survival pressure caused by antibiotics prompts bacteria to develop drug resistance. Quorum sensing is an intercellular communication system that regulates bacterial virulence and biofilm formation. In Pseudomonas aeruginosa, the formation and diffusion of biofilm is closely related to the quorum sensing system. Quorum-sensing inhibitors can reduce bacterial toxicity and enhance sensitivity to antibiotics, making them a popular topic for research and development in anti-infection. This review provides an overview of the Pseudomonas aeruginosa quorum-sensing system and quorum-sensing inhibitors research, which will aid in the future development of novel inhibitors.
Article
Biotechnology & Applied Microbiology
Yue-Xiang Zeng, Jun-Sheng Liu, Ying-Jie Wang, Shi Tang, Da-Yong Wang, Shi-Ming Deng, Ai-Qun Jia
Summary: Actinomycin D has been found to have good activity against Pseudomonas aeruginosa infection and can inhibit the bacteria's quorum sensing system. It not only reduces the production of multiple virulence factors but also loosens and flattens the bacterial biofilm structure.
WORLD JOURNAL OF MICROBIOLOGY & BIOTECHNOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Yue Liu, Jun-Jian Li, Hong-Yuan Li, Shi-Ming Deng, Ai-Qun Jia
Summary: In this study, analogs of hordenine demonstrated inhibitory activities against quorum sensing and biofilm formation in Pseudomonas aeruginosa and Serratia marcescens, with some analogs showing better activity than hordenine. Structure-activity relationship analysis indicated that the inhibitory activities of the analogs were associated with carbon chain length, presence or absence of an alpha,beta-C--C bond, amino group with/without lipophilic group, and hydroxyl group in benzene ring.
SYNTHETIC AND SYSTEMS BIOTECHNOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Kayeen Vadakkan, Ajit Kumar Ngangbam, Kuppusamy Sathishkumar, Nelson Pynadathu Rumjit, Meena Kochappan Cheruvathur
Summary: Pseudomonas aeruginosa, a competitive and biofilm organism with complex quorum systems, poses a significant threat to the medical industry. Inhibiting quorum sensing could be a potential strategy for treating bacterial infections and developing anti-virulent tools.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2024)
Article
Biotechnology & Applied Microbiology
Fatemeh Aflakian, Mehrnaz Rad, Gholamreza Hashemitabar, Milad Lagzian, Mohammad Ramezani
Summary: The novel peptides designed in this study have inhibitory effects on biofilm production and expression of related genes in Pseudomonas aeruginosa, exhibiting anti-biofilm effects at sub-inhibitory concentrations and inhibiting planktonic cell growth.
Article
Pharmacology & Pharmacy
Xuezhi Zhuo, Vito Fodera, Per Larsson, Zarah Schaal, Christel A. S. Bergstrom, Korbinian Lobmann, Aleksei Kabedev
Summary: Our previous work demonstrated that beta-lactoglobulin-stabilized amorphous solid dispersion (ASD) loaded with 70 % indomethacin remains stable for over 12 months. We further investigated the stabilization mechanisms by testing five other drug molecules and using experimental techniques and molecular dynamics simulations. The results showed that steric confinement, hydrogen bonding, and the glass transition temperature of the drug molecule play important roles in stabilizing ASDs with high drug loadings.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Sebastian Schmidt, Ulrike Holzgrabe
Summary: The binding of drugs to plasma proteins, such as human serum albumin (HSA), is crucial for determining pharmacokinetic parameters. This study investigated the enantioselective binding of S- and R-ketamine to HSA. It was found that ketamine has weak affinity to HSA, with no significant differences in binding behavior between the individual enantiomers and the racemate. The aromatic ring and N-methyl group were identified as the most strongly involved structural moieties in the binding of ketamine to HSA.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Yuchen Zhao, Han Wang, Lin Jin, Ziwei Zhang, Lianghu Liu, Mengqi Zhou, Xianzheng Zhang, Lingling Zhang
Summary: Interleukins (ILs) are important for communication between immune cells and non-immune cells, but dysregulation of ILs expression is a characteristic of autoinflammatory diseases. Drugs targeting ILs have significant clinical benefits, but may also cause adverse reactions. Fusion protein technology, with its ability to enhance therapeutic efficacy, has been explored for developing anti-inflammatory drugs. This review discusses the efficacy of fusion protein drugs developed with ILs or their receptors in treating autoinflammatory diseases, highlighting the potential of this technology in future anti-inflammatory drug development.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Serena Bertoni, Elena Simone, Stefano Sangiorgi, Beatrice Albertini, Nadia Passerini
Summary: This study investigated the correlation between the structure and release properties of solid lipid microparticles (MPs) with different liquid additives. The additives accelerated the conversion of the unstable alpha-form of tristearin to the stable beta-polymorph and caused structural modifications in the MPs. The presence of additives prolonged the drug release in water and resulted in higher release profiles in biorelevant media. The findings suggest that the release behavior can be influenced by the polymorphism and supramolecular-level structural modification of lipid formulations containing crystal modifiers.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Juulia Jarvinen, Ahmed B. Montaser, Santosh Kumar Adla, Jukka Leppanen, Marko Lehtonen, Kati-Sisko Vellonen, Tuomo Laitinen, Aaro Jalkanen, William F. Elmquist, Juri Timonen, Kristiina M. Huttunen, Jarkko Rautio
Summary: This study attempted to alter the brain distribution pattern of Palbociclib by creating and assessing two novel prodrugs. Although the prodrug design did not significantly improve Palbociclib brain delivery, the study provides valuable insights for future prodrug development and drug delivery strategies targeting specific transporters.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Review
Pharmacology & Pharmacy
Miao Wang, Xinyu Ma, Shiyu Zong, Yaqiong Su, Rui Su, Hong Zhang, Yang Liu, Chunliu Wang, Ye Li
Summary: This article discusses the potential and limitations of nasal administration in central nervous system drug delivery. Nasal gel viscosity can alleviate the impact of nasal mucociliary clearance on drug delivery, and materials such as gellan gum, chitosan, carbomer, cellulose, and poloxamer can be used to prepare nasal gels.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Bjarke Strom Larsen, Eric Kissi, Liebert Parreiras Nogueira, Natalja Genina, Ingunn Tho
Summary: This study investigates the influence of drug load and polymer molecular weight on the structure of 3D printed tablets. The results show that drug load and polymer molecular weight have a significant impact on the porosity and size of the tablets, while the effect of drug load on the total porosity of the tablets is minimal.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Zhentao Qiao, Fuhang Wang, Dongjian Han, Yuansong Zhuang, Qingjiao Jiang, Yi Zhang, Miaomiao Liu, Quanxu An, Zhiwei Wang, Deliang Shen
Summary: In this study, it was demonstrated that periadventitial delivery of rapamycin-fibrin glue (RPM-FG) can inhibit intimal hyperplasia (IH) in a rat carotid artery injury model without compromising re-endothelialization. This provides a promising direction for the future development of a safe, effective, and minimally invasive perivascular drug delivery method to treat vascular disease.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)
Article
Pharmacology & Pharmacy
Neele Puhlmann, Rodrigo Vidaurre, Klaus Kuemmerer
Summary: Active pharmaceutical ingredients and their metabolites and transformation products are pollutants that can harm human and environmental health. Designing greener APIs is an effective strategy to address this issue. The drug discovery and development process can incorporate environmental parameters to achieve this design, and this process is highly flexible.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2024)