Biology subjects

Pentland, D. R.

Publications and source records attributed to Pentland, D. R..

3 recordsLinked to original sources

bioRxiv2025

Multiscale Analysis of Candida albicans Biofilms

Candida albicans is an opportunistic fungal pathogen of significant biomedical concern. Its ability to colonize abiotic surfaces of clinical devices -- such as catheters and airway management systems -- can result in life-threatening sepsis, especially in immunocompromised patients. A deeper understanding of C. albicans biofilm development under different environmental conditions is essential for improving antifungal treatments. In this study, we examine C. albicans biofilm formation using live fluorescence microscopy across multiple scales and modalities, and introduce new quantification approaches. High-magnification tracking of hyphal tips reveals that hyphal elongation occurs intermittently rather than continuously. Using a new automated tracking approach, we show that hyphal emergence is initially rapid and slows down after approximately two hours. At lower magnifications, area coverage across large fields of view proves to be a robust and scalable metric. It is strongly influenced by seed density and extends analysis to later stages of growth. Elevated carbon dioxide levels significantly accelerate area coverage, promoting rapid biofilm expansion. Blue light illumination reduces C. albicans growth in a dose-dependent manner. Light-sheet imaging enables the long-term capture of vertical biofilm growth, complementing widefield-based approaches. We introduce logistic model parameters to effectively quantify the dynamics of surface area growth. The methodologies presented here are well-suited for high-content screening applications aimed at identifying compounds that inhibit or suppress fungal biofilm formation under clinically relevant conditions.

microbiology↗

bioRxiv2020

CO2 enhances the ability of Candida albicans to form biofilms, overcome nutritional immunity and resist antifungal treatment

C. albicans is the predominant fungal pathogen of humans and frequently colonises medical devices, such as voice prosthesis, as a biofilm. It is a dimorphic yeast that can switch between yeast and hyphal forms in response to environmental cues, a property that is essential during biofilm establishment and maturation. One such cue is the elevation of CO2 levels, as observed in exhaled breath.. However, despite the clear medical relevance, the effects of CO2 on C. albicans biofilm growth has not been investigated to date. Here, we show that physiologically relevant CO2 elevation enhances each stage of the C. albicans biofilm forming process;from attachment through to maturation and dispersion.. The effects of CO2 are mediated via the Ras/cAMP/PKA signalling pathway and the central biofilm regulators Efg1, Brg1, Bcr1 and Ndt80. Biofilms grown under elevated CO2 conditions also exhibit increased azole resistance, tolerance to nutritional immunity and enhanced glucose uptake to support their rapid growth. These findings suggest that C. albicans has evolved to utilise the CO2 signal to promote biofilm formation within the host. We investigate the possibility of targeting CO2 activated processes and propose 2-Deoxyglucose as a drug that may be repurposed to prevent C. albicans biofilm formation on medical airway management implants. We thus characterise the mechanisms by which CO2 promotes C. albicans biofilm formation and suggest new approaches for future preventative strategies.

microbiology↗

bioRxiv2019

An analysis of respiratory function and mitochondrial morphology in Candida albicans

Respiratory function and mitochondrial dynamics have been well characterised in a number of cell types, including the model yeast Saccharomyces cerevisiae, but remain under-researched in fungal pathogens such as Candida albicans. An understanding of mitochondrial activity and morphology is important if we are to understand the role that this organelle plays in adaption and response to stress. Here we examine the respiratory profiles of several prominent pathogenic Candida species and present a useful GFP probe for the study of mitochondrial morphology. We examine mitochondrial morphology under a variety of conditions that Candida species may encounter within the host, such as acidic pH, respiratory and oxidative stress. The GFP probe also allowed for the visualisation of mitochondria during hyphal development, during growth following macrophage engulfment and distribution within biofilms. These data demonstrate that the mitochondrial network of C. albicans is highly responsive to both environmental conditions and developmental cues, suggesting important roles for this organelle in environmental adaption.

cell biology↗