Paul Williams

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Verified

Paul verified their affiliation via an institutional email.

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• Ph.D
• Professor Emeritus at University of Nottingham

Background A grapevine crown gall tumor strain, Novosphingobium sp. strain Rr2-17 was previously reported to accumulate copious amounts of diverse quorum sensing signals during growth. Genome sequencing identified a single luxI homolog in strain Rr2-17, suggesting that it may encode for a AHL synthase with broad substrate range, pending functional...

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 a biofilm-resistant polymer. Materials and Methods Biofilm biomass and biomineralization on uncoate...

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 cell signaling system controlling virulence, has emerged as a promising approach as an antibiotic adj...

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, and diverse small organic molecules (primary and secondary metabolites) which are organized to optimi...

Chronic inflammation dominates disease pathogenesis in Cystic Fibrosis (CF) and there is a need to characterise CF immunity. Whole blood cultures offer a cost-effective and non-invasive approach to investigate immune responses within the host environment. Here we used whole blood cultures to investigate the differentiation potential of monocytes (C...

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 acute and chronic infections. Virulence and colonization factors are positively and negatively regula...

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 different bacterial species indicates that considerable cell-to-cell variation in the QS activation stat...

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 NagC regulates both GlcNAc biosynthesis and metabolism with GlcNAc acting as a signal that co-ordi...

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 development. Signalling via agr depends on the interaction of an autoinducing peptide (AIP) with AgrC,...

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 biosynthesis of diverse 2-alkyl-4-quinolones (AQs), of which 2-heptyl-4-hydroxyquinoline (HHQ) and 2-heptyl-...

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) generated via the initial processing of the AgrD pro-peptide by the transmembrane peptidase AgrB. S...

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 preserve the 3D location of an analyte in a sample. Polysaccharides are recognized as challenging analytes...

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 lactones (AHLs) and 2-alkyl-4-quinolones (AQs). Apparent population density-dependent phenomena such as...

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 class of shapeshifting vancomycin dimers (SVDs) that display potent activity against bacteria that a...

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 infections. Machine learning (ML) is a powerful method to find useful patterns in complex data from a...

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 discovery of novel biofilm‐resistant polymers. Herein, bacterial attachment and surface chemistry ar...

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, encrustation, and host protein deposition, which are major challenges associated with preventing C...

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 Pseudomonas aeruginosa. To achieve this, the potential of a range of recently reported, terpene-derived monom...

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 known to positively regulate the production of the major virulence factor exotoxin A and now, through...

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 known to positively regulate the production of the major virulence factor exotoxin A and now, through...

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 class of shapeshifting vancomycin dimers (SVDs) that display potent activity against bacteria that ar...

There is currently a need to develop simple biofilm models that facilitate investigation of the architecture/biology of mature bacterial biofilms in a consistent/standardized manner given their environmental and clinical importance and the need for new anti‐biofilm interventions. This study introduces a novel biofilm culture system termed the rolli...

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) and spread to humans. Here, we performed a longitudinal study in a large-scale commercial poultry...

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 development that can be attenuated via antagonists targeting the transcriptional regulator PqsR (MvfR). Here,...

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 of adults with CF were associated with adverse clinical outcomes. This is the first study to prospe...

Non-toxic, biocompatible materials that inhibit bacterial biofilm formation on implanted medical devices and so prevent infection are urgently required. Weakly amphiphilic acrylate polymers with rigid hydrocarbon pendant groups resist bacterial biofilm formation in vitro and in vivo but the biological mechanism involved is not known. By comparing b...

Bacterial biofilms represent a challenge to the healthcare system because of their resilience against antimicrobials and immune attack. Biofilms consist of bacterial aggregates embedded in an extracellular polymeric substance (EPS) composed of polysaccharides, nucleic acids and proteins. We hypothesised that carbohydrates could contribute to immune...

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 through ink-jet-based 3D printing using bacterial biofilm inhibiting formulations without the need for el...

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 most similar characterised species. However, whole-genome sequencing revealed an average nucleotide id...

Introduction. Pseudomonas aeruginosa produces quorum sensing signalling molecules including 2-alkyl-4-quinolones (AQs), which regulate virulence factor production in the cystic fibrosis (CF) airways. Hypothesis/Gap statement. Culture can lead to condition-dependent artefacts which may limit the potential insights and applications of AQs as minimall...

Pseudomonas aeruginosa produces specific signalling molecules, 2-alkyl-4-quinolones (AQs) that are de- tectable in the sputum of adults with cystic fibrosis (CF) and who have pulmonary infection with this opportunistic pathogen. This study aimed to determine whether AQs could be detected in saliva of pa- tients with CF and known infection with Pseu...

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-dimensional, surface-active materials were successfully used to control the surface properties of particle...

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 library to identify factors required for DNA release, mutants with insertions in the twin-arginine t...

P. aeruginosa (PA) continues to pose a threat to global public health due to its high levels of antimicrobial resistance (AMR). The ongoing AMR crisis has led to an alarming shortage of effective treatments for resistant microbes, and hence there is a pressing demand for the development of novel antimicrobial interventions. The potential use of ant...

Bacterial Biofilm Resistant Composite Devices Medical implants would benefit from bespoke 3D printing, however microbial infection remains a challenge. By combining functional materials, voxelated manufacturing and algorithmic design, Morgan R. Alexander, Ricky D. Wildman, and co-workers demonstrate in article number 2100249 a multi-material inkjet...

Surface topography is a tool to endow biomaterials with bioactive properties. However, the large number of possible designs makes it challenging to find the optimal surface structure to induce a specific cell response. The TopoChip platform is currently the largest collection of topographies with 2176 in silico designed microtopographies. Still, it...

As the understanding of disease grows, so does the opportunity for personalization of therapies targeted to the needs of the individual. To bring about a step change in the personalization of medical devices it is shown that multi‐material inkjet‐based 3D printing can meet this demand by combining functional materials, voxelated manufacturing, and...

Introduction Catheter associated urinary tract infections account for 40% of hospital acquired infections. They are associated with biofilms consisting of bacterial cells enmeshed in a self-generated extracellular matrix adhering to catheter surfaces. We have developed a novel polymer family that, coated onto urinary catheters, creates a “non-stick...

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. It was previously shown to inhibit or boost Aspergillus, depending on the milieu iron concentratio...

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 pipeline drying up, antivirulence therapy has become an attractive alternative strategy to the traditional...

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 protein family known to regulate N-acylhomoserine lactone (AHL) dependent QS in other β- and γ-prot...

Extracellular DNA (eDNA) is a major constituent of the extracellular matrix of Pseudomonas aeruginosa biofilms and its release is regulated via the pseudomonas quinolone signal (PQS) dependent quorum sensing (QS). By screening a P. aeruginosa transposon library to identify factors required for DNA release, mutants with insertions in the twin-argini...

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 these space missions or cultured in a microgravity analogue exhibit increased virulence, enhanced for...

Immune dysfunction has long been reported by medical professionals regarding astronauts suffering from opportunistic infections both during their time in space and a short time period afterwards once back on Earth. Various species of prokaryotes on board these space missions or cultured in a microgravity analogue exhibit increased virulence, enhanc...

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 pipeline drying up, anti-virulence therapy has become an attractive alternative strategy to the traditional...

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 protein family known to regulate N -acylhomoserine lactone (AHL) dependent QS in other β- and γ-p...

Bacterial biofilms exhibit up to 1000 times greater resistance to antibiotic or host immune clearance than planktonic cells. Pseudomonas aeruginosa produces retractable type IV pili (T4P) that facilitate twitching motility on surfaces. The deployment of pili is one of the first responses of bacteria to surface interactions and because of their abil...

The prevention of biofilm development on the surfaces of implanted medical devices is a global challenge for the healthcare sector. Bio-instructive materials that intrinsically prevent bacterial biofilm formation and drive an appropriate host immune response are required to reduce the burden of healthcare associated infections. Although bacterial s...

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 interest in pulmonary delivery, the pharmacokinetics (PK) of drugs following pulmonary administration remains to be elucidated. In this context, the...

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 examples of its use in bacteriology. In this study we show that GLuc can be functionally expressed in the human pathogen Staphylococcus aureus and furthermore show t...

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 these specific properties. A series of weakly amphiphilic monomers were combinatorially polymerized with acrylate glycol...

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 virulence attenuation where anti-virulence compounds, designed to reduce pathogenicity without affording bactericidal ef...

p>As our understanding of disease grows, it is becoming established that treatment needs to be personalized and targeted to the needs of the individual. In this paper we show that multi-material inkjet-based 3D printing, when backed with generative design algorithms, can bring a step change in the personalization of medical devices. We take cell-in...

We demonstrate the formulation of advanced functional 3D printing inks that prevent the formation of bacterial biofilms in vivo. Starting from polymer libraries, we show that a biofilm resistant object can be 3D printed with the potential for shape and cell instructive function to be selected independently. When tested in vivo, the candidate materi...

Biofilms are communities of microorganisms that attach to various surfaces and are widely associated with infections. Our investigation is focussed on a current and growing concern: the formation of biofilms in washing machines. Many countries wash clothes at reduced temperatures (30°C to 40°C) rather than at higher temperatures above 60°C that wou...

A flow-focusing microfluidic device is used to produce functionalized mono-disperse polymer particles with surface chemistries designed to control bacterial biofilm formation. This is achieved by using molecularly designed bespoke surfactants synthesized via catalytic chain transfer polymerization. This novel approach of using polymeric surfactants, o...

Secondary ion mass spectrometry (SIMS) is gaining popularity for molecular imaging in the life-sciences since it is label-free and allows imaging in two and three dimensions. The recent introduction of the OrbiSIMS has significantly improved the utility for biological imaging through combining sub-cellular spatial resolution with high-performance O...

Surface topography guides cell behavior and is a tool to endow biomaterials with bioactive properties. The large number of possible designs makes it challenging to find the optimal surface structure to induce a specific cell response. The TopoChip platform is currently the largest collection of topographies with 2176 in silico designed micro-topogr...

Current treatments for Pseudomonas aeruginosa infections are becoming less effective because of the increasing rates of multi-antibiotic resistance. Pharmacological targeting of virulence through inhibition of quorum sensing (QS) dependent virulence gene regulation has considerable therapeutic potential. In P. aeruginosa, the pqs QS system regulate...

Macrophages play a central role in orchestrating immune responses to foreign materials, which are often responsible for the failure of implanted medical devices. Material topography is known to influence macrophage attachment and phenotype, providing opportunities for the rational design of “immune‐instructive” topographies to modulate macrophage f...

Bacterial biofilms represent a challenge to the healthcare system because of their resilience against antimicrobials and immune attack. Biofilms consist of bacterial aggregates embedded in an extracellular polymeric substance (EPS) composed of carbohydrate polymers, nucleic acids and proteins. Carbohydrates within P. aeruginosa biofilms include neu...

To overcome the widespread misuse of antibiotics and reduce the growing problem of multidrug resistance, rapid, sensitive and specific novel methods to determine bacterial antibiotic susceptibility are needed. This study presents a combined dielectrophoresis (DEP) - Raman Spectroscopy (RS) method to obtain direct, real-time measurements of the susc...

Skin offers protection against external insults, with the skin microbiota playing a crucial defensive role against pathogens that gain access when the skin barrier is breached. Linkages between skin microbes, biofilms and disease have not been well established although single-species biofilm formation by skin microbiota in vitro has been extensivel...

Real time monitoring of bacterial attachment to medical devices provides opportunities to detect early biofilm formation and instigate appropriate interventions before infection develops. This study utilises long period grating (LPG) optical fibre sensors, incorporated into the lumen of endotracheal tubes (ETTs), to monitor in real time, Pseudomona...

We describe a method for label-free molecular imaging of biological materials, preserved in a native state, by using an OrbiSIMS instrument equipped with cryogenic sample handling and developing a high-pressure freezing protocol compatible with mass spectrometry. We studied the 3D distribution of quorum sensing signalling molecules, nucleobases and...

Introduction.Pseudomonas aeruginosa is an important respiratory pathogen in cystic fibrosis (CF), which is associated with an accelerated decline in lung function, frequent pulmonary exacerbations and increased mortality. P. aeruginosa produces intercellular signalling molecules including 2-alkyl-4-quinolones (AQs), which regulate virulence-factor...

Synthetic 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 of use, which means that infection is inevitable when resident for sufficient time. The O'Neill Revi...

Many debilitating infections result from persistent microbial biofilms that do not respond to conventional antibiotic regimens. A potential method to treat such chronic infections is to combine agents which interfere with bacterial biofilm development together with an antibiotic in a single formulation. Here, we explore the use of a new bioresponsi...

We have established a methodology to enable the movement of individual bacterial cells to be followed within a 3D space without requiring any labeling. Such an approach is important to observe and understand how bacteria interact with surfaces and form biofilm. We investigated the swimming behavior of Pseudomonas aeruginosa , which has two flagella...

Virulence factor expression in Staphylococcus aureus is regulated via autoinducing peptide (AIP)-dependent activation of the sensor kinase AgrC, which forms an integral part of the agr quorum sensing system. In response to bound AIP, the cytoplasmic domain of AgrC (AgrC-cyt) undergoes conformational changes resulting in dimerization, autophosphoryl...

An investigation of Pseudomonas aeruginosa attachment to a diverse range of polymers in a high-throughput microarray format resulted in the discovery of novel biofilm-resistant and biofilm-stimulating materials. These findings raised questions about the nature of the surface interactions involved and in particular the sensory mechanisms use by P. a...

Chronic wounds (CW) are a common complication of diabetic ulcers (DUs), which are a major burden to health care systems worldwide and can result in lower limb amputation due to the intractability of the infection. In DUs there is a high probability of the infecting bacteria evolving considerable phenotypic and genetic diversity, as has previously b...

Biofilms are communities of microorganisms that attach to various surfaces and are widely associated with infection for animals and plants. Our investigation is focussed on a current and growing concern: the distribution and formation of biofilms in washing machines. Many countries wash clothes at reduced temperatures around 30 to 40 °C degrees rat...

Bacterial biofilms are highly complex communities, composed of highly structured extracellular polymers and subpopulations of differentiated cells, such as persisters. These contribute to the resistance of bacterial biofilms to antibiotics, creating a significant issue in the treatment of infections and resulting in elevated levels of mortality and...

[This corrects the article DOI: 10.3389/fmicb.2018.03018.].

To better understand key behaviors of living cells, such as bacterial biofilm formation, they must be observed above surfaces and at the interface between the surface and liquid medium. We have established a methodology for label-free imaging and tracking of individual cells simultaneously at both the solid-liquid interface and within the bulk, uti...