ORCID Profile
0000-0003-3625-4021
Current Organisations
University of Nottingham
,
University of Cambridge
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Publisher: Cold Spring Harbor Laboratory
Date: 10-10-2020
DOI: 10.1101/2020.10.10.328146
Abstract: Bio-instructive materials that prevent bacterial biofilm formation and drive an appropriate host immune response have the potential to significantly reduce the burden of medical device-associated infections. Since bacterial surface attachment is known to be sensitive to surface topography, we experimentally survey 2,176 combinatorially generated shapes using an unbiased high-throughput micro topographical screen on polystyrene. This identifies topographies that reduce colonization in vitro by up to 15-fold compared with a flat surface for both motile and non-motile bacterial pathogens. Equivalent reductions are achieved on polyurethane, a polymer commonly used in medical devices. Using machine learning methods, a set of design rules based on generalisable descriptors is established for predicting bacteria-resistant micro topographies. In a murine foreign body infection model, anti-attachment topographies are shown to be refractory to P. aeruginosa and to recruit a productive host response, highlighting the potential of simple topographical patterning of non-eluting implants for preventing medical device associated infections.
Publisher: American Association for the Advancement of Science (AAAS)
Date: 27-01-2023
Abstract: 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 CAUTIs. After screening ~400 acrylate polymers, poly( tert -butyl cyclohexyl acrylate) was selected for its biofilm- and encrustation-resistant properties. When combined with the swarming inhibitory poly(2-hydroxy-3-phenoxypropyl acrylate), the copolymer retained the bioinstructive properties of the respective homopolymers when challenged with Proteus mirabilis , Pseudomonas aeruginosa , Staphylococcus aureus , and Escherichia coli . Urinary tract catheterization causes the release of host proteins that are exploited by pathogens to colonize catheters. After preconditioning the copolymer with urine collected from patients before and after catheterization, reduced host fibrinogen deposition was observed, and resistance to erse uropathogens was maintained. These data highlight the potential of the copolymer as a urinary catheter coating for preventing CAUTIs.
Publisher: American Chemical Society (ACS)
Date: 06-11-2020
Publisher: Research Square Platform LLC
Date: 31-05-2022
DOI: 10.21203/RS.3.RS-1662334/V1
Abstract: 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 erse environmental conditions. In this opportunistic pathogen, ToxR was known to positively regulate the production of the major virulence factor exotoxin A and now, through analysis of genetic changes between two sublines of P. aeruginosa PAO1 and functional complementation of swarming, we have identified a previously unknown role of ToxR in surface-associated motility in P. aeruginosa . Further analysis revealed that ToxR had an impact on swarming motility by regulating the Rhl quorum sensing system and subsequent production of rhamnolipid surfactants. Additionally, ToxR was found to tightly bind cyclic diguanylate (c-di-GMP) and negatively affect traits controlled by this second messenger including reducing biofilm formation and the expression of Psl and Pel exopolysaccharides, necessary for attachment and sessile communities’ matrix scaffolding, in P. aeruginosa . Moreover, a link between the post-transcriptional regulator RsmA and toxR expression via the alternative sigma factor PvdS, induced under iron-limiting conditions, is established. This study reveals the importance of ToxR in a novel sophisticated regulation of free-living and biofilm-associated lifestyles, appropriate for establishing acute or chronic P. aeruginosa infections.
Publisher: Springer Science and Business Media LLC
Date: 18-08-2022
DOI: 10.1038/S41522-022-00325-9
Abstract: 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 erse environmental conditions. In this opportunistic pathogen, ToxR was known to positively regulate the production of the major virulence factor exotoxin A and now, through analysis of genetic changes between two sublines of P. aeruginosa PAO1 and functional complementation of swarming, we have identified a previously unknown role of ToxR in surface-associated motility in P. aeruginosa . Further analysis revealed that ToxR had an impact on swarming motility by regulating the Rhl quorum sensing system and subsequent production of rhamnolipid surfactants. Additionally, ToxR was found to tightly bind cyclic diguanylate (c-di-GMP) and negatively affect traits controlled by this second messenger including reducing biofilm formation and the expression of Psl and Pel exopolysaccharides, necessary for attachment and sessile communities matrix scaffolding, in P. aeruginosa . Moreover, a link between the post-transcriptional regulator RsmA and toxR expression via the alternative sigma factor PvdS, induced under iron-limiting conditions, is established. This study reveals the importance of ToxR in a sophisticated regulation of free-living and biofilm-associated lifestyles, appropriate for establishing acute or chronic P. aeruginosa infections.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Alessandro Maria Carabelli.