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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., Williams, P., Cámara, M., Visca, P., Imperi, F., Leoni, L., & 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.

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.

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.

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.

Ink-jet 3D printing as a strategy for developing bespoke non-eluting biofilm resistant medical devices (2021)
Journal Article
He, Y., Luckett, J., Begines, B., Dubern, J. F., Hook, A. L., Prina, E., …Wildman, R. D. (2022). Ink-jet 3D printing as a strategy for developing bespoke non-eluting biofilm resistant medical devices. Biomaterials, 281, Article 121350. https://doi.org/10.1016/j.biomaterials.2021.121350

Chronic infection as a result of bacterial biofilm formation on implanted medical devices is a major global healthcare problem requiring new biocompatible, biofilm-resistant materials. Here we demonstrate how bespoke devices can be manufactured throu... Read More about Ink-jet 3D printing as a strategy for developing bespoke non-eluting biofilm resistant medical devices.

Actinomadura graeca sp. nov.: A novel producer of the macrocyclic antibiotic zelkovamycin (2021)
Journal Article
Tarantini, F. S., Brunati, M., Taravella, A., Carrano, L., Parenti, F., Hong, K. W., …Chan, W. C. (2021). Actinomadura graeca sp. nov.: A novel producer of the macrocyclic antibiotic zelkovamycin. PLoS ONE, 16(11), Article e0260413. https://doi.org/10.1371/journal.pone.0260413

As part of a screening programme for antibiotic-producing bacteria, a novel Actinomadura species was discovered from a soil sample collected in Santorini, Greece. Preliminary 16S rRNA gene sequence comparisons highlighted Actinomadura macra as the mo... Read More about Actinomadura graeca sp. nov.: A novel producer of the macrocyclic antibiotic zelkovamycin.

Generation and Characterization of a Library of Novel Biologically Active Functional Surfactants (Surfmers) Using Combined High-Throughput Methods (2021)
Journal Article
Cuzzucoli Crucitti, V., Contreas, L., Taresco, V., Howard, S. C., Dundas, A. A., Limo, M. J., …Irvine, D. J. (2021). Generation and Characterization of a Library of Novel Biologically Active Functional Surfactants (Surfmers) Using Combined High-Throughput Methods. ACS Applied Materials and Interfaces, 13(36), 43290-43300. https://doi.org/10.1021/acsami.1c08662

We report the first successful combination of three distinct high-throughput techniques to deliver the accelerated design, synthesis, and property screening of a library of novel, bio-instructive, polymeric, comb-graft surfactants. These three-dimens... Read More about Generation and Characterization of a Library of Novel Biologically Active Functional Surfactants (Surfmers) Using Combined High-Throughput Methods.

Disruption of the Pseudomonas aeruginosa Tat system perturbs PQS-dependent quorum sensing and biofilm maturation through lack of the Rieske cytochrome bc1sub-unit (2021)
Journal Article
Soh, E. Y.-C., Smith, F., Gimenez, M. R., Yang, L., Vejborg, R. M., Fletcher, M., …Williams, P. (2021). Disruption of the Pseudomonas aeruginosa Tat system perturbs PQS-dependent quorum sensing and biofilm maturation through lack of the Rieske cytochrome bc1sub-unit. PLoS Pathogens, 17(8), Article e1009425. https://doi.org/10.1371/journal.ppat.1009425

Extracellular DNA (eDNA) is a major constituent of the extracellular matrix of Pseudomonas aeruginosa biofilms and its release is regulated via pseudomonas quinolone signal (PQS) dependent quorum sensing (QS). By screening a P. aeruginosa transposon... Read More about Disruption of the Pseudomonas aeruginosa Tat system perturbs PQS-dependent quorum sensing and biofilm maturation through lack of the Rieske cytochrome bc1sub-unit.

Molecular modifications of the pseudomonas quinolone signal in the intermicrobial competition with aspergillus (2021)
Journal Article
Nazik, H., Sass, G., Williams, P., Déziel, E., & Stevens, D. A. (2021). Molecular modifications of the pseudomonas quinolone signal in the intermicrobial competition with aspergillus. Journal of Fungi, 7(5), Article 343. https://doi.org/10.3390/jof7050343

The Pseudomonas quinolone signal (PQS) is an important quorum-sensing molecule for Pseudomonas aeruginosa that regulates virulence factors, chelates iron, and is an important factor in interactions with eukaryotes, including fungi and mammalian hosts... Read More about Molecular modifications of the pseudomonas quinolone signal in the intermicrobial competition with aspergillus.

NirA Is an Alternative Nitrite Reductase from Pseudomonas aeruginosa with Potential as an Antivirulence Target (2021)
Journal Article
Fenn, S., Dubern, J.-F., Cigana, C., De Simone, M., Lazenby, J., Juhas, M., …Cámara, M. (2021). NirA Is an Alternative Nitrite Reductase from Pseudomonas aeruginosa with Potential as an Antivirulence Target. mBio, 12(2), Article e00207-21. https://doi.org/10.1128/mbio.00207-21

The opportunistic pathogen Pseudomonas aeruginosa produces an arsenal of virulence factors causing a wide range of diseases in multiple hosts and is difficult to eradicate due to its intrinsic resistance to antibiotics. With the antibacterial pipelin... Read More about NirA Is an Alternative Nitrite Reductase from Pseudomonas aeruginosa with Potential as an Antivirulence Target.

Immunity in space: prokaryote adaptations and immune response in microgravity (2021)
Journal Article
Green, M. J., Aylott, J. W., Williams, P., Ghaemmaghami, A. M., & Williams, P. M. (2021). Immunity in space: prokaryote adaptations and immune response in microgravity. Life, 11(2), Article 112. https://doi.org/10.3390/life11020112

Immune dysfunction has long been reported by medical professionals regarding astronauts suffering from opportunistic infections both during their time in space and a short period afterwards once back on Earth. Various species of prokaryotes onboard t... Read More about Immunity in space: prokaryote adaptations and immune response in microgravity.

AbaM Regulates Quorum Sensing, Biofilm Formation and Virulence in Acinetobacter baumannii (2021)
Journal Article
López-Martín, M., Dubern, J.-F., Alexander, M. R., & Williams, P. (2021). AbaM Regulates Quorum Sensing, Biofilm Formation and Virulence in Acinetobacter baumannii. Journal of Bacteriology, 203(8), Article e00635-20. https://doi.org/10.1128/jb.00635-20

Acinetobacter baumannii possesses a single divergent luxR/luxI-type quorum sensing (QS) locus named abaR/abaI. This locus also contains a third gene located between abaR and abaI which we term abaM that codes for an uncharacterized member of the RsaM... Read More about AbaM Regulates Quorum Sensing, Biofilm Formation and Virulence in Acinetobacter baumannii.

Model-Informed Drug Discovery and Development in Pulmonary Delivery: Biopharmaceutical Pharmacometric Modeling for Formulation Evaluation of Pulmonary Suspensions (2020)
Journal Article
Sou, T., Soukarieh, F., Williams, P., Stocks, M. J., Cámara, M., & Bergström, C. A. S. (2020). Model-Informed Drug Discovery and Development in Pulmonary Delivery: Biopharmaceutical Pharmacometric Modeling for Formulation Evaluation of Pulmonary Suspensions. ACS Omega, 5(40), 25733-25746. https://doi.org/10.1021/acsomega.0c03004

Copyright © 2020 American Chemical Society. For respiratory conditions, targeted drug delivery to the lungs could produce higher local concentrations with reduced risk of adverse events compared to systemic administration. Despite the increasing inte... Read More about Model-Informed Drug Discovery and Development in Pulmonary Delivery: Biopharmaceutical Pharmacometric Modeling for Formulation Evaluation of Pulmonary Suspensions.

Novel quinazolinone inhibitors of the Pseudomonas aeruginosa quorum sensing transcriptional regulator PqsR (2020)
Journal Article
Grossman, S., Soukarieh, F., Richardson, W., Liu, R., Mashabi, A., Emsley, J., …Stocks, M. J. (2020). Novel quinazolinone inhibitors of the Pseudomonas aeruginosa quorum sensing transcriptional regulator PqsR. European Journal of Medicinal Chemistry, 208, Article 112778. https://doi.org/10.1016/j.ejmech.2020.112778

© 2020 The Authors Rising numbers of cases of multidrug- and extensively drug-resistant Pseudomonas aeruginosa over recent years have created an urgent need for novel therapeutic approaches to cure potentially fatal infections. One such approach is v... Read More about Novel quinazolinone inhibitors of the Pseudomonas aeruginosa quorum sensing transcriptional regulator PqsR.