Publications by authors named "G Ramage"

181 Publications

Effects of Antifungal Carriers Based on Chitosan-Coated Iron Oxide Nanoparticles on Microcosm Biofilms.

Antibiotics (Basel) 2021 May 17;10(5). Epub 2021 May 17.

Graduate Program in Dentistry (GPD-Master's Degree), University of Western São Paulo (UNOESTE), Presidente Prudente 19050-920, Brazil.

Resistance of species to conventional therapies has motivated the development of antifungal nanocarriers based on iron oxide nanoparticles (IONPs) coated with chitosan (CS). This study evaluates the effects of IONPs-CS as carriers of miconazole (MCZ) or fluconazole (FLZ) on microcosm biofilms. Pooled saliva from two healthy volunteers supplemented with and was the inoculum for biofilm formation. Biofilms were formed for 96 h on coverslips using the Amsterdam Active Attachment model, followed by 24 h treatment with nanocarriers containing different concentrations of each antifungal (78 and 156 µg/mL). MCZ or FLZ (156 µg/mL), and untreated biofilms were considered as controls. Anti-biofilm effects were evaluated by enumeration of colony-forming units (CFUs), composition of the extracellular matrix, lactic acid production, and structure and live/dead biofilm cells (confocal laser scanning microscopy-CLSM). Data were analyzed by one-way ANOVA and Fisher LSD's test (α = 0.05). IONPs-CS carrying MCZ or FLZ were the most effective treatments in reducing CFUs compared to either an antifungal agent alone for and MCZ for . Significant reductions in mutans streptococci and spp. were shown, though mainly for the MCZ nanocarrier. Antifungals and their nanocarriers also showed significantly higher proportions of dead cells compared to untreated biofilm by CLSM ( < 0.001), and promoted significant reductions in lactic acid, while simultaneously showing increases in some components of the extracellular matrix. These findings reinforce the use of nanocarriers as effective alternatives to fight oral fungal infections.
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http://dx.doi.org/10.3390/antibiotics10050588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8155828PMC
May 2021

Mechanical biofilm disruption causes microbial and immunological shifts in periodontitis patients.

Sci Rep 2021 May 7;11(1):9796. Epub 2021 May 7.

Oral Sciences, Glasgow Dental Hospital and School, School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, G12 8TA, UK.

Periodontitis is characterized by subgingival biofilm dysbiosis, inflammation and tissue destruction. Current treatment involves mechanical biofilm disruption known as non-surgical periodontal therapy (NSPT). This study sought to characterise the impact of treatment on microbial diversity and overall community, and the parallel impact on host inflammation in the oral cavity. Fourty-two periodontitis patients were included in this study, with periodontal clinical parameters, subgingival plaque and saliva samples collected at baseline and 90 days after treatment. Salivary cytokines were quantified, and subgingival plaque was analysed using 16S rRNA sequencing. After treatment, there were marked health-associated alterations in microbial composition and diversity, including differential abundance of 42 genera and 61 species. These changes were accompanied by substantial clinical improvement (pockets ≥ 5 mm, 27.50% to 9.00%, p < 0.001) and a decrease in salivary IL-1β (p < 0.001)-a putative marker of periodontal inflammation. Despite significant reductions in disease associated anaerobes, several genera (Fusobacterium, Prevotella, Tanenerella, Treponema) remained present and formed a distinct subnetwork associated with residual disease. Collectively, this study shows that current periodontal treatment results in partial restoration of a healthy microbial ecosystem, but features of biofilm dysbiosis and host inflammation remain in some patients, which were surprisingly independent of clinical response.
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http://dx.doi.org/10.1038/s41598-021-89002-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8105330PMC
May 2021

Assessing the Bioactive Profile of Antifungal-Loaded Calcium Sulfate against Fungal Biofilms.

Antimicrob Agents Chemother 2021 05 18;65(6). Epub 2021 May 18.

Oral Sciences Research Group, Glasgow Dental School, School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

Calcium sulfate (CS) has been used clinically as a bone- or void-filling biomaterial, and its resorptive properties have provided the prospect for its use as a release mechanism for local antibiotics to control biofilms. Here, we aimed to test CS beads loaded with three antifungal drugs against planktonic and sessile fungal species to assess whether these antifungal beads could be harnessed to provide consistent release of antifungals at biofilm-inhibitory doses. A panel of different fungal species ( = 15) were selected for planktonic broth microdilution testing with fluconazole (FLZ), amphotericin B (AMB), and caspofungin (CSP). After establishing planktonic inhibition, antifungal CS beads were introduced to fungal biofilms ( = 5) to assess biofilm formation and cell viability through a combination of standard quantitative and qualitative biofilm assays. Inoculation of a hydrogel substrate, packed with antifungal CS beads, was also used to assess diffusion through a semidry material, to mimic active infection In general, antifungals released from loaded CS beads were all effective at inhibiting the pathogenic fungi over 7 days within standard MIC ranges for these fungi. We observed a significant reduction of pregrown fungal biofilms across key fungal pathogens following treatment, with visually observable changes in cell morphology and biofilm coverage provided by scanning electron microscopy. Assessment of biofilm inhibition also revealed reductions in total and viable cells across all organisms tested. These data show that antifungal-loaded CS beads produce a sustained antimicrobial effect that inhibits and kills clinically relevant fungal species as planktonic and biofilm cells.
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http://dx.doi.org/10.1128/AAC.02551-20DOI Listing
May 2021

Correction for Arias et al., "Chitosan Ameliorates Candida auris Virulence in a Galleria mellonella Infection Model".

Antimicrob Agents Chemother 2021 Feb 17;65(3). Epub 2021 Feb 17.

Oral Sciences Research Group, Glasgow Dental School, School of Medicine, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, United Kingdom

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http://dx.doi.org/10.1128/AAC.02560-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8092501PMC
February 2021

A curcumin-sophorolipid nanocomplex inhibits Candida albicans filamentation and biofilm development.

Colloids Surf B Biointerfaces 2021 Apr 6;200:111617. Epub 2021 Feb 6.

Faculty of Dentistry, The University of Hong Kong, Hong Kong Special Administrative Region. Electronic address:

Candida albicans is an opportunistic fungal pathogen that is highly resistant to contemporary antifungals, due to their biofilm lifestyle. The ability of C. albicans to invade human tissues is due to its filamentation. Therefore, inhibition of biofilms and filamentation of the yeast are high value targets to develop the next-generation antifungals. Curcumin (CU) is a natural polyphenol with excellent pharmacological attributes, but limitations such as poor solubility, acid, and enzyme tolerance have impeded its practical utility. Sophorolipids (SL) are biologically-derived surfactants that serve as efficient carriers of hydrophobic molecules such as curcumin into biofilms. Here, we synthesised a curcumin-sophorolipid nanocomplex (CUSL), and comprehensively evaluated its effects on C. albicans biofilms and filamentation. Our results demonstrated that sub-inhibitory concentration of CUSL (9.37 μg/mL) significantly inhibited fungal adhesion to substrates, and subsequent biofilm development, maturation, and filamentation. This effect was associated with significant downregulation of a select group of biofilm, adhesins, and hyphal regulatory genes. In conclusion, the curcumin-sophorolipid nanocomplex is a potent inhibitor of the two major virulence attributes of C. albicans, biofilm formation and filamentation, thus highlighting its promise as a putative anti-fungal agent with biofilm penetrative potential.
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http://dx.doi.org/10.1016/j.colsurfb.2021.111617DOI Listing
April 2021