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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.

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.

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.

Quantifiable correlation of ToF-SIMS and XPS data from polymer surfaces with controlled amino acid and peptide content (2022)
Journal Article
Taylor, M., Simoes, F., Smith, J., Genapathy, S., Canning, A., Lledos, M., …Zelzer, M. (2022). Quantifiable correlation of ToF-SIMS and XPS data from polymer surfaces with controlled amino acid and peptide content. Surface and Interface Analysis, 54(4), 417-432. https://doi.org/10.1002/sia.7052

Peptide-coated surfaces are widely employed in biomaterial design, but quantifiable correlation between surface composition and biological response is challenging due to, for example, instrumental limitations, a lack of suitable model surfaces or lim... Read More about Quantifiable correlation of ToF-SIMS and XPS data from polymer surfaces with controlled amino acid and peptide content.

Clostridioides difficile: innovations in target discovery and potential for therapeutic success (2021)
Journal Article
Monaghan, T. M., Seekatz, A. M., Mullish, B. H., Moore-Gillon, C. E., Dawson, L., Ahmed, A., …Chan, W. C. (2021). Clostridioides difficile: innovations in target discovery and potential for therapeutic success. Expert Opinion on Therapeutic Targets, 25(11), 949-963. https://doi.org/10.1080/14728222.2021.2008907

Introduction: Clostridioides difficile infection (CDI) remains a worldwide clinical problem. Increased incidence of primary infection, occurrence of hypertoxigenic ribotypes, and more frequent occurrence of drug resistant, recurrent, and non-hospital... Read More about Clostridioides difficile: innovations in target discovery and potential for therapeutic success.

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.

Gaussia luciferase as a reporter for quorum sensing in staphylococcus aureus (2020)
Journal Article
Blower, I., Tong, C., Sun, X., Murray, E., Luckett, J., Chan, W., …Hill, P. (2020). Gaussia luciferase as a reporter for quorum sensing in staphylococcus aureus. Sensors, 20(15), 1-12. https://doi.org/10.3390/s20154305

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Gaussia luciferase (GLuc) is a secreted protein with significant potential for use as a reporter of gene expression in bacterial pathogenicity studies. To date there are relatively few example... Read More about Gaussia luciferase as a reporter for quorum sensing in staphylococcus aureus.

Timing is everything – impact of naturally occurring Staphylococcus aureus AgrC cytoplasmic domain adaptive mutations on auto-induction (2019)
Journal Article
Sloan, T. J., Murray, E., Yokoyama, M., Massey, R. C., Chan, W. C., Bonev, B., & Williams, P. (2019). Timing is everything – impact of naturally occurring Staphylococcus aureus AgrC cytoplasmic domain adaptive mutations on auto-induction. Journal of Bacteriology, 201(20), Article e00409-19. https://doi.org/10.1128/jb.00409-19

Mutations in the polymorphic Staphylococcus aureus agr locus responsible for quorum sensing (QS) dependent virulence gene regulation occur frequently during host adaptation. In two genomically closely related S. aureus clinical isolates exhibiting ma... Read More about Timing is everything – impact of naturally occurring Staphylococcus aureus AgrC cytoplasmic domain adaptive mutations on auto-induction.

Rational design and synthesis of modified teixobactin analogues: in vitro antibacterial activity against Staphylococcus aureus, Propionibacterium acnes and Pseudomonas aeruginosa (2018)
Journal Article
Ng, V., Kuehne, S. A., & Chan, W. (in press). Rational design and synthesis of modified teixobactin analogues: in vitro antibacterial activity against Staphylococcus aureus, Propionibacterium acnes and Pseudomonas aeruginosa. Chemistry - A European Journal, 24(36), 9136-9147. https://doi.org/10.1002/chem.201801423

Teixobactin, a recently discovered depsipeptide that binds to bacterial lipid II and lipid III, provides a promising molecular scaffold for the design of new antimicrobials. Herein, we describe the synthesis and antimicrobial evaluation of systematic... Read More about Rational design and synthesis of modified teixobactin analogues: in vitro antibacterial activity against Staphylococcus aureus, Propionibacterium acnes and Pseudomonas aeruginosa.

5-Hydroxyethyl-3-tetradecanoyltetramic acid represents a novel treatment for intravascular catheter infections due to Staphylococcus aureus (2016)
Journal Article
Zapotoczna, M., Murray, E. J., Hogan, S., O'Gara, J. P., Chhabra, S. R., Chan, W. C., …Williams, P. (2017). 5-Hydroxyethyl-3-tetradecanoyltetramic acid represents a novel treatment for intravascular catheter infections due to Staphylococcus aureus. Journal of Antimicrobial Chemotherapy, 72(3), 744-753. https://doi.org/10.1093/jac/dkw482

Objectives: Biofilm infections of intravascular catheters caused by Staphylococcus aureus may be treated with catheter lock solutions (CLSs). Here we investigated the antibacterial activity, cytotoxicity and CLS potential of 5-hydroxyethyl-3-tetradec... Read More about 5-Hydroxyethyl-3-tetradecanoyltetramic acid represents a novel treatment for intravascular catheter infections due to Staphylococcus aureus.

Controlled intracellular generation of reactive oxygen species in human mesenchymal stem cells using porphyrin conjugated nanoparticles (2015)
Journal Article
Lavado, A. S., Chauhan, V. M., Alhaj Zen, A., Giuntini, F., Jones, D. R. E., Boyle, R. W., …Aylott, J. W. (2015). Controlled intracellular generation of reactive oxygen species in human mesenchymal stem cells using porphyrin conjugated nanoparticles. Nanoscale, 7(34), https://doi.org/10.1039/c5nr00795j

Nanoparticles capable of generating controlled amounts of intracellular reactive oxygen species (ROS), that advance the study of oxidative stress and cellular communication, were synthesized by functionalizing polyacrylamide nanoparticles with zinc(I... Read More about Controlled intracellular generation of reactive oxygen species in human mesenchymal stem cells using porphyrin conjugated nanoparticles.

A facile approach to tryptophan derivatives for the total synthesis of argyrin analogues (2014)
Journal Article
Chen, C.-H., Genapathy, S., Fischer, P. M., & Chan, W. C. (2014). A facile approach to tryptophan derivatives for the total synthesis of argyrin analogues. Organic and Biomolecular Chemistry, 12(48), 9764-9768. https://doi.org/10.1039/c4ob02107j

A facile route has been established for the synthesis of indole-substituted (S)-tryptophans from corresponding indoles, which utilizes a chiral auxiliary-facilitated Strecker amino acid synthesis strategy. The chiral auxiliary reagents evaluated were... Read More about A facile approach to tryptophan derivatives for the total synthesis of argyrin analogues.

An appraisal of the Suzuki cross-coupling reaction for the synthesis of novel fluorescent coumarin derivatives (2014)
Journal Article
Alhaj Zen, A., Aylott, J. W., & Chan, W. C. (2014). An appraisal of the Suzuki cross-coupling reaction for the synthesis of novel fluorescent coumarin derivatives. Tetrahedron Letters, 55(40), https://doi.org/10.1016/j.tetlet.2014.08.058

We report the chemical design and development of 3-aryl-substituted 7-alkoxy-4-methylcoumarins with enhanced fluorogenic properties. The 3-aryl substituents are installed via an optimized Suzuki–Miyaura cross-coupling (SMC) reaction between a 7-alkox... Read More about An appraisal of the Suzuki cross-coupling reaction for the synthesis of novel fluorescent coumarin derivatives.

Targeting Staphylococcus aureus quorum sensing with nonpeptidic small molecule inhibitors (2014)
Journal Article
Murray, E. J., Crowley, R. C., Truman, A., Clarke, S. R., Cottam, J. A., Jadhav, G. P., …Williams, P. (2014). Targeting Staphylococcus aureus quorum sensing with nonpeptidic small molecule inhibitors. Journal of Medicinal Chemistry, 57(6), 2813-2819. https://doi.org/10.1021/jm500215s

A series of 3-oxo-C 12 -HSL, tetramic acid, and tetronic acid analogues were synthesized to gain insights into the structural requirements for quorum sensing inhibition in Staphylococcus aureus. Compounds active against agr were noncompetitive inhibi... Read More about Targeting Staphylococcus aureus quorum sensing with nonpeptidic small molecule inhibitors.

Attenuating Staphylococcus aureus virulence gene regulation: A medicinal chemistry perspective (2013)
Journal Article
Gordon, C. P., Williams, P., & Chan, W. C. (2013). Attenuating Staphylococcus aureus virulence gene regulation: A medicinal chemistry perspective. Journal of Medicinal Chemistry, 56(4), 1389-1404. https://doi.org/10.1021/jm3014635

Virulence gene expression in Staphylococcus aureus is tightly regulated by intricate networks of transcriptional regulators and two-component signal transduction systems. There is now an emerging body of evidence to suggest that the blockade of S. au... Read More about Attenuating Staphylococcus aureus virulence gene regulation: A medicinal chemistry perspective.

Enhanced uptake of nanoparticle drug carriers via a thermoresponsive shell enhances cytotoxicity in a cancer cell line (2013)
Journal Article
Abulateefeh, S. R., Spain, S. G., Thurecht, K. J., Aylott, J. W., Chan, W. C., Garnett, M. C., & Alexander, C. (2013). Enhanced uptake of nanoparticle drug carriers via a thermoresponsive shell enhances cytotoxicity in a cancer cell line. Biomaterials Science, 1(4), 434-442. https://doi.org/10.1039/c2bm00184e

Polymer particles consisting of a biodegradable poly[lactide-co-glycolide] (PLGA) core and a thermoresponsive shell have been formulated to encapsulate the dye rhodamine 6G and the potent cytotoxic drug paclitaxel. Cellular uptake of these particles... Read More about Enhanced uptake of nanoparticle drug carriers via a thermoresponsive shell enhances cytotoxicity in a cancer cell line.

Synthetic peptides derived from an N-terminal domain of the E2 protein of GB virus C in the study of GBV-C/HIV-1 co-infection (2012)
Journal Article
Fernández, L., Chan, W. C., Egido, M., Gómara, M. J., & Haro, I. (2012). Synthetic peptides derived from an N-terminal domain of the E2 protein of GB virus C in the study of GBV-C/HIV-1 co-infection. Journal of Peptide Science, 18(5), 326-335. https://doi.org/10.1002/psc.2403

Synthetic peptides derived from GB virus C (GBV-C) have previously been studied in our group for the development of new systems capable of diagnosing diseases caused by this humanotropic virus. We also recently described specific peptide domains of t... Read More about Synthetic peptides derived from an N-terminal domain of the E2 protein of GB virus C in the study of GBV-C/HIV-1 co-infection.

Methicillin resistance reduces the virulence of healthcare-associated methicillin-resistant staphylococcus aureus by interfering with the agr quorum sensing system (2012)
Journal Article
Rudkin, J. K., Edwards, A. M., Bowden, M. G., Brown, E. L., Pozzi, C., Waters, E. M., …Massey, R. C. (2012). Methicillin resistance reduces the virulence of healthcare-associated methicillin-resistant staphylococcus aureus by interfering with the agr quorum sensing system. Journal of Infectious Diseases, 205(5), 798-806. https://doi.org/10.1093/infdis/jir845

The difficulty in successfully treating infections caused by methicillin-resistant Staphylococcus aureus (MRSA) has led to them being referred to as highly virulent or pathogenic. In our study of one of the major healthcare-associated MRSA (HA-MRSA)... Read More about Methicillin resistance reduces the virulence of healthcare-associated methicillin-resistant staphylococcus aureus by interfering with the agr quorum sensing system.

Thermoresponsive polymer colloids for drug delivery and cancer therapy (2011)
Journal Article
Abulateefeh, S. R., Spain, S. G., Aylott, J. W., Chan, W. C., Garnett, M. C., & Alexander, C. (2011). Thermoresponsive polymer colloids for drug delivery and cancer therapy. Macromolecular Bioscience, 11(12), 1722-1734. https://doi.org/10.1002/mabi.201100252

Many difficulties in treating cancer arise from the problems in directing highly cytotoxic agents to the deseased tissues, cells and intracellular compartments. Many drug delivery systems have been devised to address this problem, including those tha... Read More about Thermoresponsive polymer colloids for drug delivery and cancer therapy.

End-stapled homo and hetero collagen triple helices: A click chemistry approach (2010)
Journal Article
Byrne, C., McEwan, P. A., Emsley, J., Fischer, P. M., & Chan, W. C. (2011). End-stapled homo and hetero collagen triple helices: A click chemistry approach. Chemical Communications, 47(9), 2589-2591. https://doi.org/10.1039/c0cc04795c

A CuAAC reaction was established for modular synthesis of end-stapled homo- and hetero-triple helical peptides, generating "clicked" macro-assemblies with enhanced thermal stability. © 2011 The Royal Society of Chemistry.