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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.

Discovery of hemocompatible bacterial biofilm-resistant copolymers (2020)
Journal Article
Singh, T., Hook, A. L., Luckett, J., Maitz, M. F., Sperling, C., Werner, C., …Alexander, M. R. (2020). Discovery of hemocompatible bacterial biofilm-resistant copolymers. Biomaterials, 260, Article 120312. https://doi.org/10.1016/j.biomaterials.2020.120312

© 2020 The Authors Blood-contacting medical devices play an important role within healthcare and are required to be biocompatible, hemocompatible and resistant to microbial colonization. Here we describe a high throughput screen for copolymers with t... Read More about Discovery of hemocompatible bacterial biofilm-resistant copolymers.

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.

Microfluidic-based Growth and Imaging of Bacterial Biofilms (2019)
Journal Article
Brown, J., Blunk, B., Williams, P., & Hardie, K. (2019). Microfluidic-based Growth and Imaging of Bacterial Biofilms. Bio-protocol, 9(24), Article e3460. https://doi.org/10.21769/BioProtoc.3460

Biofilms are a ubiquitous form of growth for bacteria on surfaces in most environments, natural or manmade. Here we present a protocol using the Bioflux microfluidic system to investigate the organized structure and development of these multicellular... Read More about Microfluidic-based Growth and Imaging of Bacterial Biofilms.

Validating a Predictive Structure-Property Relationship by Discovery of Novel Polymers which Reduce Bacterial Biofilm Formation (2019)
Journal Article
Dundas, A. A., Sanni, O., Dubern, J.-F., Dimitrakis, G., Hook, A. L., Irvine, D. J., …Alexander, M. R. (2019). Validating a Predictive Structure-Property Relationship by Discovery of Novel Polymers which Reduce Bacterial Biofilm Formation. Advanced Materials, 31(49), Article 1903513. https://doi.org/10.1002/adma.201903513

ynthetic materials are an everyday component of modern healthcare yet often fail routinely as a consequence of medical‐device‐centered infections. The incidence rate for catheter‐associated urinary tract infections is between 3% and 7% for each day o... Read More about Validating a Predictive Structure-Property Relationship by Discovery of Novel Polymers which Reduce Bacterial Biofilm Formation.

Molecular recognition of lipopolysaccaride by the lantibiotic nisin (2018)
Journal Article
Lanne, A. B., Goode, A., Prattley, C., Kumari, D., Drasbek, M. R., Williams, P., …Bonev, B. B. (2019). Molecular recognition of lipopolysaccaride by the lantibiotic nisin. BBA - Biomembranes, 1861(1), 83-92. https://doi.org/10.1016/j.bbamem.2018.10.006

Nisin is a lanthionine antimicrobial effective against diverse Gram-positive bacteria and is used as a food preservative worldwide. Its action is mediated by pyrophosphate recognition of the bacterial cell wall receptors lipid II and undecaprenyl pyr... Read More about Molecular recognition of lipopolysaccaride by the lantibiotic nisin.

Model-based drug development in pulmonary delivery: pharmacokinetic analysis of novel drug candidates for treatment of Pseudomonas aeruginosa lung infection (2018)
Journal Article
Sou, T., Kukavica-Ibrulj, I., Soukarieh, F., Halliday, N., Levesque, R. C., Williams, P., …Bergström, C. A. (2019). Model-based drug development in pulmonary delivery: pharmacokinetic analysis of novel drug candidates for treatment of Pseudomonas aeruginosa lung infection. Journal of Pharmaceutical Sciences, 108(1), 630-640. https://doi.org/10.1016/j.xphs.2018.09.017

Antibiotic resistance is a major public health threat worldwide. In particular, about 80% of cystic fibrosis patients have chronic Pseudomonas aeruginosa (PA) lung infection resistant to many current antibiotics. We are therefore developing a novel c... Read More about Model-based drug development in pulmonary delivery: pharmacokinetic analysis of novel drug candidates for treatment of Pseudomonas aeruginosa lung infection.

Pseudomonas aeruginosa quorum sensing systems as drug discovery targets: current position and future perspectives (2018)
Journal Article
Soukarieh, F., Williams, P., Stocks, M. J., & Camara, M. (in press). Pseudomonas aeruginosa quorum sensing systems as drug discovery targets: current position and future perspectives. Journal of Medicinal Chemistry, https://doi.org/10.1021/acs.jmedchem.8b00540

Antimicrobial resistance (AMR) is a serious threat to public health globally, manifested by the frequent emergence of multi-drug resistant pathogens that render current chemotherapy inadequate. Health organizations worldwide have recognized the sever... Read More about Pseudomonas aeruginosa quorum sensing systems as drug discovery targets: current position and future perspectives.

The quorum sensing system of Yersinia enterocolitica 8081 regulates swimming motility, host cell attachment, and virulence plasmid maintenance (2018)
Journal Article
Ng, Y.-K., Grasso, M., Wright, V., Garcia, V., Williams, P., & Atkinson, S. (2018). The quorum sensing system of Yersinia enterocolitica 8081 regulates swimming motility, host cell attachment, and virulence plasmid maintenance. Genes, 9(6), Article 307. https://doi.org/10.3390/genes9060307

Although Yersinia enterocolitica genomes are highly heterogeneous, they contain a conserved N-acylhomoserine lactone-dependent (AHL) quorum sensing (QS) system consisting of the luxR and luxI orthologs yenR and yenI respectively. Certain hypervirulen... Read More about The quorum sensing system of Yersinia enterocolitica 8081 regulates swimming motility, host cell attachment, and virulence plasmid maintenance.

To boil an egg: substrate binding affects critical stability in thermal unfolding of proteins (2018)
Journal Article
Hussain, R., Hughes, C. S., Jávorfi, T., Siligardi, G., Williams, P., & Bonev, B. B. (2018). To boil an egg: substrate binding affects critical stability in thermal unfolding of proteins. Journal of Physical Chemistry B, 122(8), 2213-2218. https://doi.org/10.1021/acs.jpcb.7b10643

Thermal unfolding of proteins is used extensively in screening of drug candidates because molecular interactions with ligands and substrates affect strongly protein stability, transition temperature, and cooperativity. We use synchrotron radiation ci... Read More about To boil an egg: substrate binding affects critical stability in thermal unfolding of proteins.

In Silico and in Vitro-Guided Identification of Inhibitors of Alkylquinolone-Dependent Quorum Sensing in Pseudomonas aeruginosa (2018)
Journal Article
Soukarieh, F., Vico Oton, E., Dubern, J.-F., Gomes, J., Halliday, N., de Pilar Crespo, M., …Cámara, M. (2018). In Silico and in Vitro-Guided Identification of Inhibitors of Alkylquinolone-Dependent Quorum Sensing in Pseudomonas aeruginosa. Molecules, 23(2), 1-15. https://doi.org/10.3390/molecules23020257

Pseudomonas aeruginosa is a major opportunistic pathogen in cystic fibrosis, wound and nosocomial infections, posing a serious burden to public health, due to its antibiotic resistance. The P. aeruginosa Pseudomonas Quinolone System (pqs) quorum sens... Read More about In Silico and in Vitro-Guided Identification of Inhibitors of Alkylquinolone-Dependent Quorum Sensing in Pseudomonas aeruginosa.

Water contact angle is not a good predictor of biological responses to materials (2017)
Journal Article
Alexander, M. R., & Williams, P. (in press). Water contact angle is not a good predictor of biological responses to materials. Biointerphases, 12(2), Article 02C201. https://doi.org/10.1116/1.4989843

Often the view is expressed that water contact angle (WCA) or other wettability/surface energy measurements made on a material surface can be used to predict cellular attachment to materials, e.g., bacteria attach to hydrophobic surfaces. In this art... Read More about Water contact angle is not a good predictor of biological responses to materials.

Development and characterization of a stable adhesive bond between a poly(dimethylsiloxane) catheter material and a bacterial biofilm resistant acrylate polymer coating (2017)
Journal Article
Tyler, B. J., Hook, A. L., Pelster, A., Williams, P., Alexander, M. R., & Arlinghaus, H. F. (2017). Development and characterization of a stable adhesive bond between a poly(dimethylsiloxane) catheter material and a bacterial biofilm resistant acrylate polymer coating. Biointerphases, 12(2), Article 02C412. https://doi.org/10.1116/1.4984011

Catheter associated urinary tract infections (CA-UTIs) are the most common health related infections world wide, contributing significantly to patient morbidity and mortality and increased health care costs. To reduce the incidence of these infection... Read More about Development and characterization of a stable adhesive bond between a poly(dimethylsiloxane) catheter material and a bacterial biofilm resistant acrylate polymer coating.

Negative regulation of violacein biosynthesis in Chromobacterium violaceum (2017)
Journal Article
Devescovi, G., Kojic, M., Covaceuszach, S., Cámara, M., Williams, P., Bertani, I., …Venturi, V. (in press). Negative regulation of violacein biosynthesis in Chromobacterium violaceum. Frontiers in Microbiology, 8, Article 349. https://doi.org/10.3389/fmicb.2017.00349

In Chromobacteium violaceum, the purple pigment violacein is under positive regulation by the N-acylhomoserine lactone CviI/R quorum sensing system and negative regulation by an uncharacterized putative repressor. In this study we report that the bio... Read More about Negative regulation of violacein biosynthesis in Chromobacterium violaceum.

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.

Making Silicone Rubber Highly Resistant to Bacterial Attachment Using Thiol-ene Grafting (2016)
Journal Article
Magennis, E. P., Hook, A. L., Williams, P., & Alexander, M. R. (2016). Making Silicone Rubber Highly Resistant to Bacterial Attachment Using Thiol-ene Grafting. ACS Applied Materials and Interfaces, 8(45), 30780-30787. https://doi.org/10.1021/acsami.6b10986

Biomedical devices are indispensable in modern medicine yet offer surfaces that promote bacterial attachment and biofilm formation, resulting in acute and chronic healthcare-associated infections. We have developed a simple method to graft acrylates... Read More about Making Silicone Rubber Highly Resistant to Bacterial Attachment Using Thiol-ene Grafting.

Cystic Fibrosis isolates of Pseudomonas aeruginosa retain iron-regulated antimicrobial activity against Staphylococcus aureus through the action of multiple alkylquinolones (2016)
Journal Article
Nguyen, A. T., Jones, J. W., Cámara, M., Williams, P., Kane, M. A., & Oglesby-Sherrouse, A. G. (2016). Cystic Fibrosis isolates of Pseudomonas aeruginosa retain iron-regulated antimicrobial activity against Staphylococcus aureus through the action of multiple alkylquinolones. Frontiers in Microbiology, 7, https://doi.org/10.3389/fmicb.2016.01171

Cystic fibrosis (CF) is a hereditary disease that predisposes individuals to pulmonary dysfunction and chronic infections. Early infection of the CF lung with Staphylococcus aureus is common, while Pseudomonas aeruginosa becomes dominant as disease p... Read More about Cystic Fibrosis isolates of Pseudomonas aeruginosa retain iron-regulated antimicrobial activity against Staphylococcus aureus through the action of multiple alkylquinolones.

Yersinia virulence factors: a sophisticated arsenal for combating host defences (2016)
Journal Article
Atkinson, S., & Williams, P. (2016). Yersinia virulence factors: a sophisticated arsenal for combating host defences. F1000Research, 5, 1370. https://doi.org/10.12688/f1000research.8466.1

The human pathogens Yersinia pseudotuberculosis and Yersinia enterocolitica cause enterocolitis, while Yersinia pestis is responsible for pneumonic, bubonic, and septicaemic plague. All three share an infection strategy that relies on a virulence fac... Read More about Yersinia virulence factors: a sophisticated arsenal for combating host defences.