Article
Biochemistry & Molecular Biology
Selene Garcia-Reyes, Miguel Cocotl-Yanez, Martin Paolo Soto-Aceves, Abigail Gonzalez-Valdez, Luis Servin-Gonzalez, Gloria Soberon-Chavez
Summary: This study characterized the PqsE-dependent production of PYO in Pseudomonas aeruginosa ATCC 9027 and found that PqsE promotes the RhlR-dependent production of PYO, although this production is not strictly dependent on PqsE. The interaction between PqsE and RhlR modifies the transcription of genes involved in PYO production, highlighting the variability of the quorum-sensing response among different P. aeruginosa clades and strains.
MOLECULAR MICROBIOLOGY
(2021)
Article
Microbiology
Morgana Letizia, Marta Mellini, Alessandra Fortuna, Paolo Visca, Francesco Imperi, Livia Leoni, Giordano Rampioni
Summary: This study investigates the regulatory link between the pqs and rhl QS systems mediated by PqsE and RhlR in Pseudomonas aeruginosa. The results show that PqsE mainly impacts the P. aeruginosa transcriptome via an RhlR-dependent pathway and splits the RhlR regulon into PqsE-dependent and PqsE-independent subregulons.
MICROBIOLOGY SPECTRUM
(2022)
Article
Microbiology
Shouyi Li, Xuetao Gong, Liwen Yin, Xiaolei Pan, Yongxin Jin, Fang Bai, Zhihui Cheng, Un-Hwan Ha, Weihui Wu
Summary: This study reveals a novel regulatory mechanism in Pseudomonas aeruginosa, where CspC protein regulates the quorum-sensing systems by repressing the translation of a negative regulator gene, rsaL, in response to a host-generated metabolite.
Article
Biochemistry & Molecular Biology
Wenjie Cai, Huimin Liao, Mingqi Lu, Xiangting Zhou, Xiaoyan Cheng, Christian Staehelin, Weijun Dai
Summary: This study developed an experimental evolutionary approach to identify additional determinants for quorum-sensing (QS) reprogramming in Pseudomonas aeruginosa. The study revealed a new functional role for RpoA in regulating QS activity and identified a RpoA-dependent regulatory circuit critical for QS-reprogramming.
MOLECULAR BIOLOGY AND EVOLUTION
(2023)
Article
Biochemistry & Molecular Biology
Chaoyue Zhao, Hongda Zheng, Liman Zhou, Hongrui Ji, Lu Zhao, Wengong Yu, Qianhong Gong
Summary: Falcarindiol, a component of Notopterygium incisum, showed inhibitory effects on biofilm formation and virulence factor production in Pseudomonas aeruginosa by downregulating QS-related genes and destabilizing LasR, providing a theoretical basis for its medicinal application as a potential anti-virulence agent.
Article
Biotechnology & Applied Microbiology
Adilson Jose da Silva, Josivan de Souza Cunha, Teri Hreha, Kelli Cristina Micocci, Heloisa Sobreiro Selistre-de-Araujo, Blanca Barquera, Mattheos A. G. Koffas
Summary: This study engineered the pyocyanin biosynthetic pathway for high production in a heterologous host for the first time. Optimized culture and induction parameters led to a 3.5-fold increase in pyocyanin accumulation, while pathway balancing through testing plasmids with different copy numbers resulted in a fourfold difference in product titer among the engineered strains. Co-expression of Vitreoscilla hemoglobin Vhb further improved pyocyanin production to a final titer of 18.8 mg/L, demonstrating the potential of using Escherichia coli for phenazines production in electro-fermentation systems.
METABOLIC ENGINEERING
(2021)
Article
Microbiology
Marta Mellini, Morgana Letizia, Lorenzo Caruso, Alessandra Guiducci, Carlo Meneghini, Stephan Heeb, Paul Williams, Miguel Camara, Paolo Visca, Francesco Imperi, Livia Leoni, Giordano Rampioni
Summary: Quorum sensing allows single cells to synchronize gene expression in bacterial populations, but studies have shown significant cell-to-cell variation in this process, resulting in coexisting subpopulations of active and inactive cells. The molecular mechanisms behind this phenomenon, particularly in the las QS system of Pseudomonas aeruginosa, have not been fully defined.
Article
Microbiology
Wouter A. G. Beenker, Jelmer Hoeksma, Marie Bannier-Helaouet, Hans Clevers, Jeroen den Hertog
Summary: Antibiotics are losing effectiveness against bacterial infections due to the rise of resistance in bacteria. Pseudomonas aeruginosa is a Gram-negative pathogen that is difficult to treat because of its high inherent resistance to antimicrobial agents. Therefore, new treatment targets are needed, with one interesting approach being to target quorum sensing.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biochemistry & Molecular Biology
Silvia Schinner, Matthias Preusse, Christopher Kesthely, Susanne Haeussler
Summary: The overlapping genes encoding the major Pseudomonas aeruginosa quorum-sensing regulator, LasR, and its opponent, RsaL, have a system of checks and balances to prevent dominant and unilateral control by LasR over RsaL. Although complementary RNA is produced, it does not interfere with gene expression levels, showing that the natural organization with partial overlap at the 3' ends plays an important role in avoiding excessive interference and one-sided control.
MOLECULAR MICROBIOLOGY
(2021)
Article
Multidisciplinary Sciences
Martin Schuster, Christina Li, Parker Smith, Christina Kuttler
Summary: Quorum sensing in bacteria is a widespread process that controls collective behaviors through the perception of self-produced chemical signals. This study integrates experiments with mathematical modeling to analyze the LasI/LasR quorum sensing pathway in Pseudomonas aeruginosa, revealing its bistable hysteretic switch behavior and the significance of feedback architecture.
JOURNAL OF THE ROYAL SOCIETY INTERFACE
(2023)
Article
Biotechnology & Applied Microbiology
Xiaoyan Cheng, Mingqi Lu, Huifang Qiu, Yuanhao Li, Linfeng Huang, Weijun Dai
Summary: In this study, the QS phenotypes and genetic basis of laboratory PAO1 strains were systematically investigated using QS reporter and whole-genome sequencing (WGS). It was found that the PAO1-z strain carries an inactive LasR protein but an active Rhl QS system, and an 18-bp insertion in the mexT gene gives rise to the active QS system in the PAO1-z strain.
Article
Microbiology
Isabelle R. Taylor, Laura A. Murray-Nerger, Todd M. Greco, Dawei Liu, Ileana M. Cristea, Bonnie L. Bassler
Summary: This study reveals specific protein interactions involving PqsE and the role of RhlR in these interactions. These findings contribute to the understanding of the pathogenic mechanisms and quorum sensing process in Pseudomonas aeruginosa.
Article
Biochemistry & Molecular Biology
Theerthankar Das, Shekh Sabir, Ren Chen, Jessica Farrell, Frederik H. Kriel, Gregory S. Whiteley, Trevor O. Glasbey, Jim Manos, Mark D. P. Willcox, Naresh Kumar
Summary: The study found that halogenated dihydropyrrol-2-ones (DHP) compounds were able to inhibit the quorum-sensing system of Pseudomonas aeruginosa, reducing biofilm formation and virulence factor production. Halogenated DHPs showed better inhibitory effects compared to non-halogenated DHP.
Article
Chemistry, Multidisciplinary
Eleanor R. Clifford, Robert W. Bradley, Laura T. Wey, Joshua M. Lawrence, Xiaolong Chen, Christopher J. Howe, Jenny Z. Zhang
Summary: The research demonstrates that using low-midpoint potential phenazines can improve energy conversion efficiency in photosynthetic bioelectrochemical systems. Adjusting the concentration of the mediator is necessary to prevent undesirable side reactions and avoid toxicity to biological cells.
Article
Microbiology
Vijay K. K. Singh, Marianna Almpani, Kelsey M. M. Wheeler, Laurence G. G. Rahme
Summary: Pseudomonas aeruginosa is a common multidrug-resistant bacterial pathogen that poses a serious threat to critically ill and immunocompromised patients. Intestinal colonization by this pathogen is associated with increased mortality rates. In this study, the role of the three major communication systems in P. aeruginosa was investigated, and it was found that the MvfR system plays a key role in intestinal inflammation while the other systems have relatively minor effects. This study reveals the interrelationships of the quorum sensing systems during infection and provides important insights for developing effective antivirulence strategies.
Article
Biochemical Research Methods
Zixin Peng, Alexandre Maciel-Guerra, Michelle Baker, Xibin Zhang, Yue Hu, Wei Wang, Jia Rong, Jing Zhang, Ning Xue, Paul Barrow, David Renney, Dov Stekel, Paul Williams, Longhai Liu, Junshi Chen, Fengqin Li, Tania Dottorini
Summary: This study conducted a long-term investigation in a large-scale commercial poultry farm in China and found highly interrelated non-pathogenic and pathogenic Escherichia coli strains with a high prevalence of multidrug resistance profiles. Through an original data processing method, the study investigated the resistance to 26 different antimicrobials and identified 361 genes associated with antimicrobial resistance phenotypes. It also found shared mobile genetic elements carrying antimicrobial resistance genes among humans, livestock, and the environment.
PLOS COMPUTATIONAL BIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Jean-Frederic Dubern, Manuel Romero, Anne Mai-Prochnow, Marco Messina, Eleftheria Trampari, Hardeep Naghra-van Gijzel, Kok-Gan Chan, Alessandro M. Carabelli, Nicolas Barraud, James Lazenby, Ye Chen, Shaun Robertson, Jacob G. Malone, Paul Williams, Stephan Heeb, Miguel Camara
Summary: Pseudomonas aeruginosa uses multiple protein regulators, including ToxR, to control the production of virulence factors and adapt to different environments. This study reveals the previously unknown role of ToxR in surface-associated motility and its impact on the Rhl quorum sensing system and biofilm formation in P. aeruginosa.
NPJ BIOFILMS AND MICROBIOMES
(2022)
Article
Biochemistry & Molecular Biology
Valentina Cuzzucoli Crucitti, Aleksandar Ilchev, Jonathan C. Moore, Harriet R. Fowler, Jean-Frederic Dubern, Olutoba Sanni, Xuan Xue, Bethany K. Husband, Adam A. Dundas, Sean Smith, Joni L. Wildman, Vincenzo Taresco, Paul Williams, Morgan R. Alexander, Steven M. Howdle, Ricky D. Wildman, Robert A. Stockman, Derek J. Irvine
Summary: This study utilized the alpha parameter, a molecular descriptor, to design terpene-based polymers resistant to biofilm formation by Pseudomonas aeruginosa. The potential biofilm resistance of terpene-derived monomers was predicted and ranked using the alpha parameter. The monomers from commercially available terpenes were polymerized and confirmed to have biofilm resistance properties. The scaled-up monomers were successfully printed and used to create bio-instructive microparticles. The observations in this study have significant potential to produce bio-resistant coatings, packaging materials, fibers, and medical devices.
Article
Multidisciplinary Sciences
Jean-Frederic Dubern, Andrew L. Hook, Alessandro M. Carabelli, Chien-Yi Chang, Christopher A. Lewis-Lloyd, Jeni C. Luckett, Laurence Burroughs, Adam A. Dundas, David J. Humes, Derek J. Irvine, Morgan R. Alexander, Paul Williams
Summary: Innovative approaches are urgently needed to prevent catheter-associated urinary tract infections (CAUTIs). A newly discovered acrylate copolymer has shown promising resistance against bacterial biofilm formation, swarming, encrustation, and host protein deposition, all of which are major challenges in preventing CAUTIs. The copolymer, poly(tert-butyl cyclohexyl acrylate), combined with poly(2-hydroxy-3-phenoxypropyl acrylate) has demonstrated its potential as a urinary catheter coating by retaining its bioinstructive properties and maintaining resistance against various uropathogens.
Article
Nanoscience & Nanotechnology
Leonardo Contreas, Andrew L. Hook, David A. Winkler, Grazziela Figueredo, Paul Williams, Charles A. Laughton, Morgan R. Alexander, Philip M. Williams
Summary: Bacterial infections are becoming a greater concern due to antimicrobial resistance. The rational design of materials resistant to biofilm formation is a crucial strategy to prevent infections related to medical devices. Machine learning has been used to identify strong associations between bacterial adhesion and the physicochemical properties of polyacrylate libraries. However, the interpretability of nonlinear models is limited, making it challenging to understand the molecular interactions between materials and bacteria.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Biophysics
Heba Khateb, Andrew L. Hook, Stefanie Kern, Julie A. Watts, Sonali Singh, Darryl Jackson, Luisa Marinez-Pomares, Paul Williams, Morgan R. Alexander
Summary: The use of OrbiTrap analyzer with SIMS (3D OrbiSIMS) enables label-free mass spectrometry of Psl, accurately identifying secondary ion peaks specific to the Psl structure. By studying P. aeruginosa biofilm and purified Psl, 17 peaks associated with Psl fragments within the biofilm matrix were confidently identified. Additionally, the neutral loss sequences approach can also identify multiple oligosaccharide fragments without a biological reference sample.
Article
Microbiology
Jean-Frederic Dubern, Nigel Halliday, Miguel Camara, Klaus Winzer, David A. Barrett, Kim R. Hardie, Paul Williams
Summary: Quorum sensing (QS) in Pseudomonas aeruginosa relies on the Las, Rhl, and Pqs systems to regulate the synthesis of AHLs and AQs. While QS is commonly thought to be population density-dependent, this study demonstrates that growth rate and population density independently modulate the accumulation of AHLs and AQs. Different nutrient limitations, temperature, and mutation of key QS genes also affect the production of AHLs and AQs in P. aeruginosa. QS imposes an energetic drain on the bacterium by consuming key substrates and ATP.
Article
Multidisciplinary Sciences
Alessandra Ottonello, Jessica A. Wyllie, Oussama Yahiaoui, Shoujun Sun, Rebecca A. Koelln, Joshua A. Homer, Robert M. Johnson, Ewan Murray, Paul Williams, Jani R. Bolla, Carol Robinson, Thomas Fallon, Tatiana P. Soares da Costa, John E. Moses
Summary: The rise of drug-resistant superbugs poses a significant global health hazard. A new class of shapeshifting vancomycin dimers has been synthesized, which shows potent activity against drug-resistant bacteria. These shapeshifting antibiotics have the ability to inhibit bacterial cell wall biosynthesis and are not easily affected by common resistance mechanisms.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
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
See Yoong Wong, Andrew L. Hook, Wil Gardner, Chien-Yi Chang, Ying Mei, Martyn C. Davies, Paul Williams, Morgan R. Alexander, Davide Ballabio, Benjamin W. Muir, David A. Winkler, Paul J. Pigram
Summary: Biofilm formation is a major problem in hospitals, and researching biofilm-resistant materials is critical. Polymer microarrays can efficiently discover new biofilm-resistant polymers. This study investigates bacterial attachment and surface chemistry on a polymer microarray to better understand Pseudomonas aeruginosa biofilm formation. Analyzing the data using linear multivariate analysis and a nonlinear self-organizing map reveals fragment ions associated with bacterial biofilm formation. Considering these insights, a second analysis is conducted that explicitly considers interactions between key fragments. This improved model provides chemical insights for designing materials that prevent pathogen attachment.
ADVANCED MATERIALS INTERFACES
(2023)
Article
Chemistry, Multidisciplinary
Philip Bardelang, Ewan J. Murray, Isobel Blower, Sara Zandomeneghi, Alice Goode, Rohanah Hussain, Divya Kumari, Giuliano Siligardi, Katsuaki Inoue, Jeni Luckett, James Doutch, Jonas Emsley, Weng C. Chan, Philip Hill, Paul Williams, Boyan B. Bonev
Summary: The virulence gene expression in S. aureus is controlled by the agr quorum sensing system, and the AgrB and AgrD proteins play important roles in this process. Through homology modelling and molecular dynamics techniques, the conformations of AgrB and AgrD were characterized and their interaction mechanisms were analyzed. Experimental evidence confirmed the direct interaction between AgrB and AgrD, and the formation of AgrBD complex in vitro. These findings contribute to a better understanding of the mechanisms behind the regulation of virulence gene expression in S. aureus.
FRONTIERS IN CHEMISTRY
(2023)
Article
Microbiology
Diletta Collalto, Alessandra Fortuna, Paolo Visca, Francesco Imperi, Giordano Rampioni, Livia Leoni
Summary: Co-administration of colistin and clofoctol enhances the bactericidal effect of colistin and reduces the minimum inhibitory concentration (MIC) of colistin in resistant strains. This study suggests the potential development of inhaled clofoctol-colistin formulations for the treatment of difficult-to-treat airway infections caused by drug-resistant Gram-negative pathogens.
MICROBIOLOGY SPECTRUM
(2023)
Article
Biochemistry & Molecular Biology
Macauley J. Green, Ewan J. Murray, Paul Williams, Amir M. Ghaemmaghami, Jonathan W. Aylott, Philip M. Williams
Summary: Under low-shear modeled microgravity conditions, Staphylococcus aureus exhibited a colonization phenotype instead of a pathogenic one, due to reduced production of autoinducing peptide signal molecules.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Microbiology
Marta Mellini, Morgana Letizia, Lorenzo Caruso, Alessandra Guiducci, Carlo Meneghini, Stephan Heeb, Paul Williams, Miguel Camara, Paolo Visca, Francesco Imperi, Livia Leoni, Giordano Rampioni
Summary: Quorum sensing allows single cells to synchronize gene expression in bacterial populations, but studies have shown significant cell-to-cell variation in this process, resulting in coexisting subpopulations of active and inactive cells. The molecular mechanisms behind this phenomenon, particularly in the las QS system of Pseudomonas aeruginosa, have not been fully defined.
Article
Biochemistry & Molecular Biology
Ewan J. Murray, Jean-Frederic Dubern, Weng C. Chan, Siri Ram Chhabra, Paul Williams
Summary: In this study, the researchers discovered that the PqsR inhibitor QZN 34 can prevent the biofilm formation of Staphylococcus aureus, damage established S. aureus biofilms, and interfere with the biofilm development of Pseudomonas aeruginosa. The combination of the aminoglycoside antibiotic tobramycin with QZN 34 can effectively eradicate mixed-species biofilms.
CELL CHEMICAL BIOLOGY
(2022)