Article
Chemistry, Multidisciplinary
Cansu Kaya, Isabell Walter, Samir Yahiaoui, Asfandyar Sikandar, Alaa Alhayek, Jelena Konstantinovic, Andreas M. Kany, Jorg Haupenthal, Jesko Koehnke, Rolf W. Hartmann, Anna K. H. Hirsch
Summary: Extracellular virulence factors, including the LasB enzyme secreted by the Gram-negative pathogen Pseudomonas aeruginosa, have become important targets in the current antimicrobial resistance crisis. In this study, a sub-micromolar, non-peptidic inhibitor of LasB was discovered through structural data analysis and optimization, showing improved in vivo efficacy in Galleria mellonella larvae. This class of compounds shows promise as potential drug candidates for combating infections.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Review
Biotechnology & Applied Microbiology
Geum-Jae Jeong, Fazlurrahman Khan, Sohail Khan, Nazia Tabassum, Sonu Mehta, Young-Mog Kim
Summary: Pseudmonas aeruginosa is a widespread Gram-negative bacterium responsible for infections in various parts of the body. The development of multiple resistance mechanisms has led to failure of antimicrobial therapy. Inhibition of siderophore production in P. aeruginosa has emerged as a promising therapeutic option to limit their infection.
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Christian Emmanuel Mahavy, Adeline Mol, Blandine Andrianarisoa, Pierre Duez, Mondher El Jaziri, Marie Baucher, Tsiry Rasamiravaka
Summary: Lutein-type compounds can inhibit biofilm formation and invasion capabilities of Pseudomonas aeruginosa, reduce the production of virulence factors, and enhance the bactericidal activity of antibiotics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Immunology
Chongbing Liao, Xin Huang, Qingxia Wang, Dan Yao, Wuyuan Lu
Summary: Pseudomonas aeruginosa is a pathogen that causes nosocomial infections, particularly in severely ill and immunocompromised patients. It is widely distributed in the environment, especially in hospitals, and poses a major threat to human health due to the emergence of drug-resistant strains. The use of antivirulence treatment or combination therapies can effectively reduce virulence without inducing drug resistance.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2022)
Article
Microbiology
Yang Yuan, Xiting Yang, Qianglin Zeng, Heyue Li, Ruyi Fu, Lianming Du, Wei Liu, Yamei Zhang, Xikun Zhou, Yiwen Chu, Xiuyue Zhang, Kelei Zhao
Summary: This study reports the antivirulence potentials of Dimetridazole and Ribavirin on Pseudomonas aeruginosa and provides structural basis and methodological reference for the development of anti-pseudomonal drugs. The two compounds significantly inhibit the growth and production of virulence factors in P. aeruginosa, and enhance the susceptibility of drug-resistant strains to existing antibiotics. Moreover, they effectively protect animal models from P. aeruginosa infection.
FRONTIERS IN MICROBIOLOGY
(2022)
Article
Microbiology
Sadaf Soltani, Bibi Sedigheh Fazly Bazzaz, Farzin Hadizadeh, Fatemeh Roodbari, Vahid Soheili
Summary: Vitamin E and K-1 exhibit significant anti-biofilm activity and effectively inhibit the expression of virulence factors in Pseudomonas aeruginosa. The combination of these vitamins with tobramycin reduces the number of bacteria sheltered inside biofilms. This study suggests the potential use of these vitamins as antivirulence agents against multidrug-resistant bacteria.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
(2021)
Article
Chemistry, Multidisciplinary
Soo Khim Chan, Zhongchao Zhao, Samuel Penziner, Ethan Khong, David Pride, Robert T. Schooley, Nicole F. Steinmetz
Summary: Antimicrobial resistance is a global health threat exacerbated by the misuse of antibiotics in medicine and agriculture. Phage therapy, as an alternative antimicrobial treatment, involves using bacteriophages to destroy bacterial pathogens. This study aimed to develop versatile tools for tracking and imaging phages by screening and isolating peptides that bind to specific phages.
Article
Chemistry, Medicinal
Fazlurrahman Khan, Min-Gyun Kang, Du-Min Jo, Pathum Chandika, Won-Kyo Jung, Hyun Wook Kang, Young-Mog Kim
Summary: Synthesis of gold and zinc oxide nanoparticles using pure phloroglucinol and their application in combating Pseudomonas aeruginosa, effectively inhibiting biofilm formation and reducing virulence factors of the pathogen.
Article
Engineering, Biomedical
Ziv Azoulay, Polina Aibinder, Ayala Gancz, Jacob Moran-Gilad, Shiri Navon-Venezia, Hanna Rapaport
Summary: FKF, a tripeptide with potential antimicrobial activity, forms a pure peptide hydrogel phase made of natural amino acids. The hydrogel exhibits bactericidal activity against E. coli and P. aeruginosa, and reduces P. aeruginosa contamination in a rat skin lesion model.
ACTA BIOMATERIALIA
(2021)
Article
Immunology
Kang Shun, Sun Ying-Li, Li Zhi-juan, Li Jian-liang, Xiao Feng, Dong Lu-jiao, Yuan Peng, Shijin Jiang, Xie Zhi-jing
Summary: H9N2 IAV infection contributes to severe hemorrhagic pneumonia and coinfection with P. aeruginosa in mink. This study investigates the innate immune responses to P. aeruginosa LPS stimulation following H9N2 IAV infection using an in vitro alveolar macrophage model. The results show that LPS stimulation exacerbates inflammatory responses and apoptosis in MH-S cells with H9N2 IAV infection, and also influences H9N2 IAV replication.
MICROBIAL PATHOGENESIS
(2023)
Article
Microbiology
Kimberly K. Kajihara, Homer Pantua, Hilda Hernandez-Barry, Meredith Hazen, Kiran Deshmukh, Nancy Chiang, Rachana Ohri, Erick R. Castellanos, Lynn Martin, Marissa L. Matsumoto, Jian Payandeh, Kelly M. Storek, Kellen Schneider, Peter A. Smith, Michael F. T. Koehler, Siao Ping Tsai, Richard Vandlen, Kelly M. Loyet, Gerald Nakamura, Thomas Pillow, Dhaya Seshasayee, Sharookh B. Kapadia, Wouter L. W. Hazenbos
Summary: This study demonstrates that an anti-P. aeruginosa AAC can locally concentrate antibiotic and kill P. aeruginosa inside phagocytes, providing additional therapeutic options for antibiotics that are moderately active or have an unfavorable pharmacokinetics or toxicity profile. This approach may provide new therapeutic options for antibiotics that are dose limited.
Article
Chemistry, Applied
Rajesh P. Shastry, Saptami Kanekar, Aleema Suzna Pandial, P. D. Rekha
Summary: Isoeugenol is shown to be an effective inhibitor of quorum sensing regulated phenotypes and biofilm formation in Pseudomonas aeruginosa, with more than 70% inhibition of virulence factors. The presence of isoeugenol did not affect planktonic cells, but significantly inhibited biofilm formation through binding interactions with quorum sensor regulators. This suggests the potential of isoeugenol as a blocker of quorum sensing and an antivirulence compound.
NATURAL PRODUCT RESEARCH
(2022)
Article
Chemistry, Medicinal
Martin J. Everett, David T. Davies, Simon Leiris, Nicolas Sprynski, Agustina Llanos, Jerome M. Castandet, Clarisse Lozano, Christopher N. LaRock, Doris L. LaRock, Giuseppina Corsica, Jean-Denis Docquier, Thomas D. Pallin, Andrew Cridland, Toby Blench, Magdalena Zalacain, Marc Lemonnier
Summary: This study describes the chemical optimization of specific LasB inhibitors and their impact in cellular and animal models of P. aeruginosa infection. Competitive inhibition of LasB was demonstrated through structural and kinetic studies. The highly potent and soluble LasB inhibitors show clear potential for the clinical development of a novel therapy for life-threatening respiratory infections caused by P. aeruginosa.
ACS INFECTIOUS DISEASES
(2023)
Article
Environmental Sciences
Zeyang Lian, Zuoyi Yang, Weifeng Song, Mengge Sun, Yu Gan, Xiaoyan Bai
Summary: EPS production is a self-protection mechanism that helps microorganisms counteract adverse effects in unfavorable environments. The study found that protein content in EPS was the highest, and Cd(II) stress significantly increased EPS production in two strains of bacteria. The stress also led to the formation of specific chemical moieties. The addition of Cd(NO3)(2) effectively regulated EPS components, especially protein content, and improved adsorption capacity.
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
(2022)
Article
Mathematics, Interdisciplinary Applications
Bahatdin Dasbasi
Summary: A model using fractional-order differential equations is proposed to examine the dynamics of susceptible and resistant bacteria, adaptive immunity cells, and innate cells in an infected individual receiving multiple antibiotics and antivirulence drug therapy. The model's existence, uniqueness, non-negativity, and boundedness of solutions are discussed. Reproduction numbers are developed to assess the model, and the existence and stability of equilibrium points are shown. Numerical simulations using parameter values for Mycobacterium Tuberculosis (Mtb) and Pseudomonas Aeruginosa (Pa) are conducted to demonstrate the model's applicability to real-world examples, and the effects of antivirulence drug therapy in addition to antibiotic therapy are investigated. The role of antivirulence drug therapy in eliminating infectious bacteria is discussed based on the simulation results obtained from the recommended treatment processes for these bacteria. Sensitivity analysis of the reproduction numbers is performed based on the values used in the simulations.
CHAOS SOLITONS & FRACTALS
(2023)
Review
Biochemistry & Molecular Biology
Preeti Garai, Anne Blanc-Potard
MOLECULAR MICROBIOLOGY
(2020)
Review
Biochemistry & Molecular Biology
Anne-Beatrice Blanc-Potard, Eduardo A. Groisman
Summary: Host organisms use nutritional immunity to restrict the availability of essential nutrients to invading pathogens, with magnesium deprivation playing a significant role in limiting the growth of Salmonella enterica serovar Typhimurium in host tissues. Pathogens' responses to factors promoting nutritional immunity may be more reflective of their internal cytoplasmic environment rather than the nutrient concentration in host cell compartments.
TRENDS IN MICROBIOLOGY
(2021)
Article
Multidisciplinary Sciences
Malika Moussouni, Laurence Berry, Tamara Sipka, Mai Nguyen-Chi, Anne-Beatrice Blanc-Potard
Summary: The study demonstrates that a P. aeruginosa oprF mutant is attenuated in zebrafish embryos with functional macrophages, but not due to increased macrophage recruitment or enhanced phagocytosis. Additionally, inhibition of acidification increases embryo sensitivity to both wild-type and oprF mutant, partially reversing the attenuation caused by oprF mutation.
SCIENTIFIC REPORTS
(2021)
Article
Pharmacology & Pharmacy
Isabel Ferreiro, Coralie Genevois, Karidia Konate, Eric Vives, Prisca Boisguerin, Sebastien Deshayes, Franck Couillaud
Summary: The study demonstrates the in vivo efficiency of WRAP5:siRNA nanoparticles delivering siRNA to cancer cells in solid tumors, achieving specific gene silencing through RNA interference and significantly downregulating the expression of firefly luciferase, with no toxicity and sustained presence in the tumor for at least 10 days.
Article
Microbiology
Eliza Ye-Chen Soh, Frances Smith, Maxime Remi Gimenez, Liang Yang, Rebecca Munk Vejborg, Matthew R. Fletcher, Nigel Halliday, Sophie Bleves, Stephan Heeb, Miguel R. Camara, Michael Givskov, Kim R. R. Hardie, Tim Tolker-Nielsen, Berengere R. Ize, Paul Williams
Summary: The study revealed that perturbation of the twin-arginine translocation (Tat) pathway in P. aeruginosa led to defective biofilm architecture, increased susceptibility to antibiotics, and disrupted pseudomonas quinolone signal (PQS) transmission, resulting in altered production and release of biofilm components.
Article
Polymer Science
Ruben Faria, Eric Vives, Prisca Boisguerin, Angela Sousa, Diana Costa
Summary: Mitochondria are cellular organelles that produce cellular energy in the form of ATP. Mutations in the mitochondrial DNA can lead to various disorders, prompting the exploration of gene therapy as a promising treatment approach. Targeting mitochondria using mitochondrial DNA and peptide-based complexes shows potential for restoring normal mitochondrial function and advancing mitochondrial gene therapy.
Review
Biochemistry & Molecular Biology
Prisca Boisguerin, Karidia Konate, Emilie Josse, Eric Vives, Sebastien Deshayes
Summary: Gene therapy offers the potential to address faulty genes by delivering therapeutic nucleic acids or stimulating the immune system, but the delivery of these exogenous nucleic acids remains a challenge. Cell-penetrating peptides are gaining interest as delivery systems for their ability to form a variety of nanocomplexes, with common features including defined formulation conditions for optimal delivery.
Review
Immunology
Stephane Pont, Anne-Beatrice Blanc-Potard
Summary: Pseudomonas aeruginosa is an opportunistic human pathogen responsible for acute infections and a major cause of mortality in CF patients. The zebrafish embryo model is a powerful tool to study P. aeruginosa pathogenesis and host immune response, especially in a CF context.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2021)
Article
Immunology
Zachary N. Phillips, Preeti Garai, Greg Tram, Gael Martin, Annelies Van den Bergh, Asma-Ul Husna, Megan Staples, Keith Grimwood, Amy Jennison, Patrice Guillon, Mark von Itzstein, Michael P. Jennings, Kenneth L. Brockman, John M. Atack
Summary: Lay is an autotransporter protein found in pathogenic Haemophilus and Neisseria species. Its expression status is reversible and related to pathogenicity in non-typeable Haemophilus influenzae. Understanding the role of Lay can provide insights into different pathological processes.
INFECTION AND IMMUNITY
(2022)
Article
Pharmacology & Pharmacy
Quentin Seisel, Israpong Lakumpa, Emilie Josse, Eric Vives, Jessica Varilh, Magali Taulan-Cadars, Prisca Boisguerin
Summary: Therapeutic peptides have regained interest as they can address unmet medical needs and can be an excellent complement to pharmaceutic small molecules and other macromolecular therapeutics. In this study, the optimization of a peptidyl inhibitor and the screening of cell-penetrating peptides resulted in the identification of an optimal peptide for CFTR stabilization. Using this peptide, an additive increase in CFTR amount was observed when combined with a small-molecule treatment. This finding is significant for the development of CFTR-stabilizing peptides as additional treatments for CF patients.
Article
Pharmacology & Pharmacy
Ruben Faria, Milan Paul, Swati Biswas, Eric Vives, Prisca Boisguerin, Angela Sousa, Diana Costa
Summary: Mitochondria have their own genome and mutations in mitochondrial DNA can lead to various diseases. Developing a gene delivery system specifically targeting mitochondria is crucial for mitochondrial gene therapy. This study compared polymer- and peptide-based systems and found that peptides have a better capability to complex with DNA, forming smaller particles suitable for cellular transfection and mitochondrial gene therapy.
Article
Pharmacology & Pharmacy
Ana Raquel Neves, Tania Albuquerque, Ruben Faria, Ana M. Goncalves, Cecilia Santos, Eric Vives, Prisca Boisguerin, Luis A. Passarinha, Angela Sousa, Diana Costa
Summary: Despite progress in cancer diagnosis and treatment, glioblastoma remains the most lethal brain tumor. Gene therapy focused on non-viral vectors, such as transferrin (Tf), has been developed as a promising approach. In this study, a cell-penetrating peptide (WRAP5) targeting Tf was used to condense tumor suppressor p53-encoding plasmid DNA (pDNA), forming nanocomplexes. These complexes showed efficient cellular internalization, gene expression, and decreased viability of glioblastoma cells.
Article
Cell & Tissue Engineering
Gautier Tejedor, Prisca Boisguerin, Eric Vives, Christian Jorgensen, Jerome Guicheux, Claire Vinatier, Claire Gondeau, Farida Djouad
Summary: An interfering peptide was designed and synthesized to enhance the immunoregulatory properties of mesenchymal stem cells.
STEM CELLS INTERNATIONAL
(2022)
Article
Multidisciplinary Sciences
Jona Karam, Fabien P. Blanchet, Eric Vives, Prisca Boisguerin, Yves-Marie Boudehen, Laurent Kremer, Wassim Daher
Summary: It has been discovered that neutralizing anti-CD81 antibodies and deletion of the large extracellular loop (LEL) of CD81 significantly reduce the uptake of Mab by macrophages. Saturation of Mab with soluble GST-CD81-LEL or CD81-LEL-derived peptides also decreases the internalization of the bacteria. The study unveils AhpC as a major interactant of CD81-LEL, and pre-exposure of macrophages with soluble AhpC inhibits mycobacterial uptake while overexpression of AhpC in Mab enhances its internalization. These findings highlight the previously unexplored role of CD81/AhpC in promoting the uptake of pathogenic mycobacteria by host cells.