Publications by authors named "Angela H Nobbs"

Orthopedic implant-related bacterial infections and resultant antibiotic-resistant biofilms hinder implant-tissue integration and failure. Biofilm quorum sensing (QS) communication determines the pathogen colonization success. However, it remains unclear how implant modifications and host cells are influenced by, or influence, QS.

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The design and construction of continuous flow biochemical reactors comprising immobilized biocatalysts have generated great interest in the efficient synthesis of value-added chemicals. Living cells use compartmentalization and reaction-diffusion processes for spatiotemporal regulation of biocatalytic reactions, and implementing these strategies into continuous flow reactors can offer new opportunities in reactor design and application. Herein, the fabrication of protocell-based continuous flow reactors for enzyme and whole-cell mediated biocatalysis is demonstrated.

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Novel strategies employing mechano-transducing materials eliciting biological outcomes have recently emerged for controlling cellular behaviour. Targeted cellular responses are achieved by manipulating physical, chemical, or biochemical modification of material properties. Advances in techniques such as nanopatterning, chemical modification, biochemical molecule embedding, force-tuneable materials, and artificial extracellular matrices are helping understand cellular mechanotransduction.

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and other closely related pathogenic yeast-like fungi carry on their surface numerous loosely adsorbed "moonlighting proteins"-proteins that play evolutionarily conserved intracellular functions but also appear on the cell surface and exhibit additional functions, e.g., contributing to attachment to host tissues.

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Bioinspired nanotopography is a promising approach to generate antimicrobial surfaces to combat implant-associated infection. Despite efforts to develop bactericidal 1D structures, the antibacterial capacity of 2D structures and their mechanism of action remains uncertain. Here, hydrothermal synthesis is utilized to generate two 2D nanoflake surfaces on titanium (Ti) substrates and investigate the physiological effects of nanoflakes on bacteria.

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Medical implant-associated infections pose a significant challenge to modern medicine, with aseptic loosening and bacterial infiltration being the primary causes of implant failure. While nanostructured surfaces have demonstrated promising antibacterial properties, the translation of their efficacy from 2D to 3D substrates remains a challenge. Here, we used scalable alkaline etching to fabricate nanospike and nanonetwork topologies on 2D and laser powder-bed fusion printed 3D titanium.

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Bacterial fibrillar adhesins are specialized extracellular polypeptides that promote the attachment of bacteria to the surfaces of other cells or materials. Adhesin-mediated interactions are critical for the establishment and persistence of stable bacterial populations within diverse environmental niches and are important determinants of virulence. The fibronectin (Fn)-binding fibrillar adhesin CshA, and its paralogue CshB, play important roles in host colonization by the oral commensal and opportunistic pathogen Streptococcus gordonii.

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Nature-inspired antimicrobial surfaces and antimicrobial peptides (AMPs) have emerged as promising strategies to combat implant-associated infections. In this study, a bioinspired antimicrobial peptide was functionalized onto a nanospike (NS) surface by physical adsorption with the aim that its gradual release into the local environment would enhance inhibition of bacterial growth. Peptide adsorbed on a control flat surface exhibited different release kinetics compared to the nanotopography, but both surfaces showed excellent antibacterial properties.

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Extracellular DNA (eDNA) is a key component of many microbial biofilms including dental plaque. However, the roles of extracellular deoxyribonuclease (DNase) enzymes within biofilms are poorly understood. Streptococcus gordonii is a pioneer colonizer of dental plaque.

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Streptococcus agalactiae, otherwise known as Group B Streptococcus (GBS), is an opportunistic pathogen that vaginally colonizes approximately one third of healthy women. During pregnancy, this can lead to infection, resulting in premature rupture of membranes, chorioamnionitis, and stillbirths. Furthermore, GBS causes serious infection in newborns, including sepsis, pneumonia, and meningitis.

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Article Synopsis
  • Extracellular DNA (eDNA) is a key component of biofilm structures, aiding in structural integrity, gene exchange, and protection against antimicrobials, though current assessment methods for eDNA are insufficient.
  • This study developed a new imaging and analysis platform that effectively measures eDNA networks within biofilms, specifically using Streptococcus gordonii to validate the system's capability.
  • The research revealed interactions between eDNA and glucans, as well as regulatory mechanisms affecting eDNA release, suggesting that this imaging technology could greatly enhance our understanding of biofilm dynamics and therapeutic strategies.
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Dental plaque is the key etiological agent in caries formation and the development of the prevalent chronic oral inflammatory disease, periodontitis. The dental plaque biofilm comprises a diverse range of microbial species encased within a rich extracellular matrix, of which extracellular DNA (eDNA) has been identified as an important component. The molecular mechanisms of eDNA release and the structure of eDNA have yet to be fully characterized.

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Dental implants are an increasingly popular way to replace missing teeth. Whilst implant survival rates are high, a small number fail soon after placement, with various factors, including bacterial contamination, capable of disrupting osseointegration. This work describes the development of chlorhexidine-hexametaphosphate coatings for titanium that hydrolyse to release the antiseptic agent chlorhexidine.

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One of defense mechanisms of the human immune system to counteract infection by the opportunistic fungal pathogen is the recruitment of neutrophils to the site of invasion, and the subsequent production of neutrophil extracellular traps (NETs) that efficiently capture and kill the invader cells. In the current study, we demonstrate that within these structures composed of chromatin and proteins, the latter play a pivotal role in the entrapment of the fungal pathogen. The proteinous components of NETs, such as the granular enzymes elastase, myeloperoxidase and lactotransferrin, as well as histones and cathelicidin-derived peptide LL-37, are involved in contact with the surface of cells.

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To robustly assess the antibacterial mechanisms of nanotopographies, it is critical to analyze the bacteria-nanotopography adhesion interface. Here, we utilize focused ion beam milling combined with scanning electron microscopy to generate three-dimensional reconstructions of or interacting with nanotopographies. For the first time, 3D morphometric analysis has been exploited to quantify the intrinsic contact area between each nanostructure and the bacterial envelope, providing an objective framework from which to derive the possible antibacterial mechanisms of synthetic nanotopographies.

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Nanopillared surfaces have emerged as a promising strategy to combat bacterial infections on medical devices. However, the mechanisms that underpin nanopillar-induced rupture of the bacterial cell membrane remain speculative. In this study, we have tested three medically relevant poly(ethylene terephthalate) (PET) nanopillared-surfaces with well-defined nanotopographies against both Gram-negative and Gram-positive bacteria.

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Streptococci are Gram-positive bacteria that belong to the natural microbiota of humans and animals. Certain streptococcal species are known as opportunistic pathogens with the potential to cause severe invasive disease. Antigen I/II (AgI/II) family proteins are sortase anchored cell surface adhesins that are nearly ubiquitous across streptococci and contribute to many streptococcal diseases, including dental caries, respiratory tract infections, and meningitis.

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The multifunctional protein enolase has repeatedly been identified on the surface of numerous cell types, including a variety of pathogenic microorganisms. In Candida albicans-one of the most common fungal pathogens in humans-a surface-exposed enolase form has been previously demonstrated to play an important role in candidal pathogenicity. In our current study, the presence of enolase at the fungal cell surface under different growth conditions was examined, and a higher abundance of enolase at the surface of C.

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To cause infection, must withstand damage caused by host immune defenses. However, the mechanisms by which staphylococcal DNA is damaged and repaired during infection are poorly understood. Using a panel of transposon mutants, we identified the operon as being important for the survival of in whole human blood.

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Glycosylation of proteins, previously thought to be absent in prokaryotes, is increasingly recognized as important for both bacterial colonization and pathogenesis. For mucosal pathobionts, glycoproteins that function as cell wall-associated adhesins facilitate interactions with mucosal surfaces, permitting persistent adherence, invasion of deeper tissues and transition to disease. This is exemplified by and , which can switch from being relatively harmless members of the mucosal tract microbiota to bona fide pathogens that cause life-threatening diseases.

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(group B streptococcus; GBS) is a colonizer of the gastrointestinal and urogenital tracts, and an opportunistic pathogen of infants and adults. The worldwide population of GBS is characterized by clonal complexes (CCs) with different invasive potentials. CC17, for example, is a hypervirulent lineage commonly associated with neonatal sepsis and meningitis, while CC1 is less invasive in neonates and more commonly causes invasive disease in adults with comorbidities.

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The cell surfaces of many bacteria carry filamentous polypeptides termed adhesins that enable binding to both biotic and abiotic surfaces. Surface adherence is facilitated by the exquisite selectivity of the adhesins for their cognate ligands or receptors and is a key step in niche or host colonization and pathogenicity. is a primary colonizer of the human oral cavity and an opportunistic pathogen, as well as a leading cause of infective endocarditis in humans.

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Background: Syndecans are heparan sulfate proteoglycans that occur in membrane-bound or soluble forms. Syndecan-3, the least well-characterised of the syndecan family, is highly expressed on synovial endothelial cells in rheumatoid arthritis patients. Here, it binds pro-inflammatory chemokines with evidence for a role in chemokine presentation and leukocyte trafficking into the joint, promoting the inflammatory response.

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Streptococcus agalactiae (Group B Streptococcus, GBS) normally colonizes healthy adults but can cause invasive disease, such as meningitis, in the newborn. To gain access to the central nervous system, GBS must interact with and penetrate brain or meningeal blood vessels; however, the exact mechanisms are still being elucidated. Here, we investigate the contribution of BspC, an antigen I/II family adhesin, to the pathogenesis of GBS meningitis.

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The oral cavity contains different types of microbial species that colonize human host via extensive cell-to-cell interactions and biofilm formation. Candida albicans-a yeast-like fungus that inhabits mucosal surfaces-is also a significant colonizer of subgingival sites in patients with chronic periodontitis. It is notable however that one of the main infectious agents that causes periodontal disease is an anaerobic bacterium-Porphyromonas gingivalis.

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