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Polymer-Coated Urinary Catheter Reduces Biofilm Formation and Biomineralization: A First-in-Man, Prospective Pilot Study (2024)
Journal Article
Kalenderski, K., Dubern, J., Lewis-Lloyd, C., Jeffery, N., Heeb, S., Irvine, D. J., …Williams, P. (2024). Polymer-Coated Urinary Catheter Reduces Biofilm Formation and Biomineralization: A First-in-Man, Prospective Pilot Study. Journal of Urology Open PLus, 2(1), Article e00005. https://doi.org/10.1097/JU9.0000000000000097

Purpose: Biofilm formation and biomineralization on urinary catheters may cause severe complications including infection and obstruction. Here, we describe an in vitro evaluation and prospective pilot clinical study of a silicone catheter coated with... Read More about Polymer-Coated Urinary Catheter Reduces Biofilm Formation and Biomineralization: A First-in-Man, Prospective Pilot Study.

Design, Synthesis, and Evaluation of New 1H-Benzo[d]imidazole Based PqsR Inhibitors as Adjuvant Therapy for Pseudomonas aeruginosa Infections (2024)
Journal Article
Soukarieh, F., Mashabi, A., Richardson, W., Oton, E. V., Romero, M., Dubern, J., …Cámara, M. (2024). Design, Synthesis, and Evaluation of New 1H-Benzo[d]imidazole Based PqsR Inhibitors as Adjuvant Therapy for Pseudomonas aeruginosa Infections. Journal of Medicinal Chemistry, 67(2), 1008-1023. https://doi.org/10.1021/acs.jmedchem.3c00973

Pseudomonas aeruginosa is one of the top priority pathogens that requires immediate attention according to the World Health Organisation (WHO). Due to the alarming shortage of novel antimicrobials, targeting quorum sensing (QS), a bacterial cell to c... Read More about Design, Synthesis, and Evaluation of New 1H-Benzo[d]imidazole Based PqsR Inhibitors as Adjuvant Therapy for Pseudomonas aeruginosa Infections.

Toward Comprehensive Analysis of the 3D Chemistry of Pseudomonas aeruginosa Biofilms (2023)
Journal Article
Kotowska, A. M., Zhang, J., Carabelli, A., Watts, J., Aylott, J. W., Gilmore, I. S., …Alexander, M. R. (2023). Toward Comprehensive Analysis of the 3D Chemistry of Pseudomonas aeruginosa Biofilms. Analytical Chemistry, 95(49), 18287-18294. https://doi.org/10.1021/acs.analchem.3c04443

Bacterial biofilms are structured communities consisting of cells enmeshed in a self-generated extracellular matrix usually attached to a surface. They contain diverse classes of molecules including polysaccharides, lipids, proteins, nucleic acids, a... Read More about Toward Comprehensive Analysis of the 3D Chemistry of Pseudomonas aeruginosa Biofilms.

Modelled-Microgravity Reduces Virulence Factor Production in Staphylococcus aureus through Downregulation of agr-Dependent Quorum Sensing (2023)
Journal Article
Green, M. J., Murray, E. J., Williams, P., Ghaemmaghami, A. M., Aylott, J. W., & Williams, P. M. (2023). Modelled-Microgravity Reduces Virulence Factor Production in Staphylococcus aureus through Downregulation of agr-Dependent Quorum Sensing. International Journal of Molecular Sciences, 24(21), Article 15997. https://doi.org/10.3390/ijms242115997

Bacterial contamination during space missions is problematic for human health and damages filters and other vital support systems. Staphylococcus aureus is both a human commensal and an opportunistic pathogen that colonizes human tissues and causes a... Read More about Modelled-Microgravity Reduces Virulence Factor Production in Staphylococcus aureus through Downregulation of agr-Dependent Quorum Sensing.

RsaL-driven negative regulation promotes heterogeneity in Pseudomonas aeruginosa quorum sensing (2023)
Journal Article
Mellini, M., Letizia, M., Caruso, L., Guiducci, A., Meneghini, C., Heeb, S., …Rampioni, G. (2023). RsaL-driven negative regulation promotes heterogeneity in Pseudomonas aeruginosa quorum sensing. mBio, 14(6), Article e02039-23. https://doi.org/10.1128/mbio.02039-23

In its canonical interpretation, quorum sensing (QS) allows single cells in a bacterial population to synchronize gene expression and hence perform specific tasks collectively once the quorum cell density is reached. However, growing evidence in diff... Read More about RsaL-driven negative regulation promotes heterogeneity in Pseudomonas aeruginosa quorum sensing.

Reciprocal regulation of NagC and quorum sensing systems and their roles in hmsHFRS expression and biofilm formation in Yersinia pseudotuberculosis (2023)
Journal Article
Wiechmann, A., Garcia, V., Elton, L., Williams, P., & Atkinson, S. (2023). Reciprocal regulation of NagC and quorum sensing systems and their roles in hmsHFRS expression and biofilm formation in Yersinia pseudotuberculosis. Microbiology, 169(10), Article 001397. https://doi.org/10.1099/mic.0.001397

Biofilm formation by Yersinia pseudotuberculosis is regulated by quorum sensing (QS) and dependent on the haemin storage locus hms, required for the extracellular polysaccharide poly-N-acetylglucosamine (poly-GlcNAc) production. In Escherichia coli N... Read More about Reciprocal regulation of NagC and quorum sensing systems and their roles in hmsHFRS expression and biofilm formation in Yersinia pseudotuberculosis.

Quorum-sensing, intra- and inter-species competition in the staphylococci (2023)
Journal Article
Williams, P., Hill, P., Bonev, B., & Chan, W. C. (2023). Quorum-sensing, intra- and inter-species competition in the staphylococci. Microbiology, 169(8), https://doi.org/10.1099/mic.0.001381

In Gram-positive bacteria such as Staphylococcus aureus and the coagulase-negative staphylococci (CoNS), the accessory gene regulator (agr) is a highly conserved but polymorphic quorum-sensing system involved in colonization, virulence and biofilm de... Read More about Quorum-sensing, intra- and inter-species competition in the staphylococci.

Identification of Pseudomonas aeruginosa exopolysaccharide Psl in biofilms using 3D OrbiSIMS (2023)
Journal Article
Khateb, H., Hook, A. L., Kern, S., Watts, J. A., Singh, S., Jackson, D., …Alexander, M. R. (2023). Identification of Pseudomonas aeruginosa exopolysaccharide Psl in biofilms using 3D OrbiSIMS. Biointerphases, 18(3), Article 031007. https://doi.org/10.1116/6.0002604

Secondary ion mass spectrometry (SIMS) offers advantages over both liquid extraction mass spectrometry and matrix assisted laser desorption mass spectrometry in that it provides the direct in situ analysis of molecules and has the potential to preser... Read More about Identification of Pseudomonas aeruginosa exopolysaccharide Psl in biofilms using 3D OrbiSIMS.

Alkyl-quinolone-dependent quorum sensing controls prophage-mediated autolysis in Pseudomonas aeruginosa colony biofilms (2023)
Journal Article
Giallonardi, G., Letizia, M., Mellini, M., Frangipani, E., Halliday, N., Heeb, S., …Rampioni, G. (2023). Alkyl-quinolone-dependent quorum sensing controls prophage-mediated autolysis in Pseudomonas aeruginosa colony biofilms. Frontiers in Cellular and Infection Microbiology, 13, Article 1183681. https://doi.org/10.3389/fcimb.2023.1183681

Pseudomonas aeruginosa is a model quorum sensing (QS) pathogen with three interconnected QS circuits that control the production of virulence factors and antibiotic tolerant biofilms. The pqs QS system of P. aeruginosa is responsible for the biosynth... Read More about Alkyl-quinolone-dependent quorum sensing controls prophage-mediated autolysis in Pseudomonas aeruginosa colony biofilms.

Conformational analysis and interaction of the Staphylococcus aureus transmembrane peptidase AgrB with its AgrD propeptide substrate (2023)
Journal Article
Bardelang, P., Murray, E. J., Blower, I., Zandomeneghi, S., Goode, A., Hussain, R., …Bonev, B. B. (2023). Conformational analysis and interaction of the Staphylococcus aureus transmembrane peptidase AgrB with its AgrD propeptide substrate. Frontiers in Chemistry, 11, Article 1113885. https://doi.org/10.3389/fchem.2023.1113885

Virulence gene expression in the human pathogen, S. aureus is regulated by the agr (accessory gene regulator) quorum sensing (QS) system which is conserved in diverse Gram-positive bacteria. The agr QS signal molecule is an autoinducing peptide (AIP)... Read More about Conformational analysis and interaction of the Staphylococcus aureus transmembrane peptidase AgrB with its AgrD propeptide substrate.

Growth rate and nutrient limitation as key drivers of extracellular quorum sensing signal molecule accumulation in Pseudomonas aeruginosa (2023)
Journal Article
Dubern, J., Halliday, N., Cámara, M., Winzer, K., Barrett, D. A., Hardie, K. R., & Williams, P. (2023). Growth rate and nutrient limitation as key drivers of extracellular quorum sensing signal molecule accumulation in Pseudomonas aeruginosa. Microbiology, 169(4), Article 001316. https://doi.org/10.1099/mic.0.001316

In Pseudomonas aeruginosa, quorum sensing (QS) depends on an interconnected regulatory hierarchy involving the Las, Rhl and Pqs systems, which are collectively responsible for the co-ordinated synthesis of a diverse repertoire of N-acylhomoserine lac... Read More about Growth rate and nutrient limitation as key drivers of extracellular quorum sensing signal molecule accumulation in Pseudomonas aeruginosa.

Shapeshifting bullvalene-linked vancomycin dimers as effective antibiotics against multidrug-resistant gram-positive bacteria (2023)
Journal Article
Ottonello, A., Wyllie, J. A., Yahiaoui, O., Sun, S., Koelln, R. A., Homer, J. A., …Moses, J. E. (2023). Shapeshifting bullvalene-linked vancomycin dimers as effective antibiotics against multidrug-resistant gram-positive bacteria. Proceedings of the National Academy of Sciences, 120(15), Article e2208737120. https://doi.org/10.1073/pnas.2208737120

The alarming rise in superbugs that are resistant to drugs of last resort, including vancomycin-resistant enterococci and staphylococci, has become a significant global health hazard. Here, we report the click chemistry synthesis of an unprecedented... Read More about Shapeshifting bullvalene-linked vancomycin dimers as effective antibiotics against multidrug-resistant gram-positive bacteria.

Linear Binary Classifier to Predict Bacterial Biofilm Formation on Polyacrylates (2023)
Journal Article
Contreas, L., Hook, A. L., Winkler, D. A., Figueredo, G., Williams, P., Laughton, C. A., …Williams, P. M. (2023). Linear Binary Classifier to Predict Bacterial Biofilm Formation on Polyacrylates. ACS Applied Materials and Interfaces, 15(11), 14155-14163. https://doi.org/10.1021/acsami.2c23182

Bacterial infections are increasingly problematic due to the rise of antimicrobial resistance. Consequently, the rational design of materials naturally resistant to biofilm formation is an important strategy for preventing medical device-associated i... Read More about Linear Binary Classifier to Predict Bacterial Biofilm Formation on Polyacrylates.

Exploring the Relationship between Polymer Surface Chemistry and Bacterial Attachment Using ToF-SIMS and Self-Organizing maps (2023)
Journal Article
Wong, S. Y., Hook, A. L., Gardner, W., Chang, C., Mei, Y., Davies, M. C., …Pigram, P. J. (2023). Exploring the Relationship between Polymer Surface Chemistry and Bacterial Attachment Using ToF-SIMS and Self-Organizing maps. Advanced Materials Interfaces, 10(9), Article 2202334. https://doi.org/10.1002/admi.202202334

Biofilm formation is a major cause of hospital-acquired infections. Research into biofilm-resistant materials is therefore critical to reduce the frequency of these events. Polymer microarrays offer a high-throughput approach to enable the efficient... Read More about Exploring the Relationship between Polymer Surface Chemistry and Bacterial Attachment Using ToF-SIMS and Self-Organizing maps.

Discovery of a polymer resistant to bacterial biofilm, swarming, and encrustation (2023)
Journal Article
Dubern, J. F., Hook, A. L., Carabelli, A. M., Chang, C. Y., Lewis-Lloyd, C. A., Luckett, J. C., …Williams, P. (2023). Discovery of a polymer resistant to bacterial biofilm, swarming, and encrustation. Science Advances, 9(4), Article eadd7474. https://doi.org/10.1126/sciadv.add7474

Innovative approaches to prevent catheter-associated urinary tract infections (CAUTIs) are urgently required. Here, we describe the discovery of an acrylate copolymer capable of resisting single- and multispecies bacterial biofilm formation, swarming... Read More about Discovery of a polymer resistant to bacterial biofilm, swarming, and encrustation.

Predictive Molecular Design and Structure–Property Validation of Novel Terpene-Based, Sustainably Sourced Bacterial Biofilm-Resistant Materials (2023)
Journal Article
Cuzzucoli Crucitti, V., Ilchev, A., Moore, J. C., Fowler, H. R., Dubern, J., Sanni, O., …Irvine, D. J. (2023). Predictive Molecular Design and Structure–Property Validation of Novel Terpene-Based, Sustainably Sourced Bacterial Biofilm-Resistant Materials. Biomacromolecules, https://doi.org/10.1021/acs.biomac.2c00721

Presented in this work is the use of a molecular descriptor, termed the α parameter, to aid in the design of a series of novel, terpene-based, and sustainable polymers that were resistant to biofilm formation by the model bacterial pathogen Pseudomon... Read More about Predictive Molecular Design and Structure–Property Validation of Novel Terpene-Based, Sustainably Sourced Bacterial Biofilm-Resistant Materials.

ToxR is a c-di-GMP binding protein that modulates surface-associated behaviour in Pseudomonas aeruginosa (2022)
Journal Article
Camara, M., Dubern, J., Romero, M., Mai-Prochnow, A., Messina, M., Trampari, E., …Heeb, S. (2022). ToxR is a c-di-GMP binding protein that modulates surface-associated behaviour in Pseudomonas aeruginosa. npj Biofilms and Microbiomes, 8, Article 64. https://doi.org/10.1038/s41522-022-00325-9

Pseudomonas aeruginosa uses multiple protein regulators that work in tandem to control the production of a wide range of virulence factors and facilitate rapid adaptation to diverse environmental conditions. In this opportunistic pathogen, ToxR was k... Read More about ToxR is a c-di-GMP binding protein that modulates surface-associated behaviour in Pseudomonas aeruginosa.

A Pseudomonas aeruginosa PQS quorum-sensing system inhibitor with anti-staphylococcal activity sensitizes polymicrobial biofilms to tobramycin (2022)
Journal Article
Murray, E. J., Dubern, J., Chan, W. C., Chhabra, S. R., & Williams, P. (2022). A Pseudomonas aeruginosa PQS quorum-sensing system inhibitor with anti-staphylococcal activity sensitizes polymicrobial biofilms to tobramycin. Cell Chemical Biology, 29(7), 1187-1199.e6. https://doi.org/10.1016/j.chembiol.2022.02.007

As single- and mixed-species biofilms, Staphylococcus aureus and Pseudomonas aeruginosa cause difficult-to-eradicate chronic infections. In P. aeruginosa, pseudomonas quinolone (PQS)-dependent quorum sensing regulates virulence and biofilm developmen... Read More about A Pseudomonas aeruginosa PQS quorum-sensing system inhibitor with anti-staphylococcal activity sensitizes polymicrobial biofilms to tobramycin.

Whole-genome sequencing and gene sharing network analysis powered by machine learning identifies antibiotic resistance sharing between animals, humans and environment in livestock farming (2022)
Journal Article
Peng, Z., Maciel-Guerra, A., Baker, M., Zhang, X., Hu, Y., Wang, W., …Dottorini, T. (2022). Whole-genome sequencing and gene sharing network analysis powered by machine learning identifies antibiotic resistance sharing between animals, humans and environment in livestock farming. PLoS Computational Biology, 18(3), Article e1010018. https://doi.org/10.1371/journal.pcbi.1010018

Anthropogenic environments such as those created by intensive farming of livestock, have been proposed to provide ideal selection pressure for the emergence of antimicrobial-resistant Escherichia coli bacteria and antimicrobial resistance genes (ARGs... Read More about Whole-genome sequencing and gene sharing network analysis powered by machine learning identifies antibiotic resistance sharing between animals, humans and environment in livestock farming.

Porphyromonas pasteri and Prevotella nanceiensis in the sputum microbiota are associated with increased decline in lung function in individuals with cystic fibrosis (2022)
Journal Article
Webb, K., Zain, N. M. M., Stewart, I., Fogarty, A., Nash, E. F., Whitehouse, J. L., …Barr, H. L. (2022). Porphyromonas pasteri and Prevotella nanceiensis in the sputum microbiota are associated with increased decline in lung function in individuals with cystic fibrosis. Journal of Medical Microbiology, 71(2), Article 001481. https://doi.org/10.1099/jmm.0.001481

Although anaerobic bacteria exist in abundance in cystic fibrosis (CF) airways, their role in disease progression is poorly understood. We hypothesized that the presence and relative abundance of the most prevalent, live, anaerobic bacteria in sputum... Read More about Porphyromonas pasteri and Prevotella nanceiensis in the sputum microbiota are associated with increased decline in lung function in individuals with cystic fibrosis.