Latest Publications
Mike Tildesley publications
The impact of natural climate variability on the global distribution of Aedes aegypti : a mathematical modelling study
Kaye, A. R., Obolski, U., Sun, L., Hart, W. S., Hurrell, J. W., Tildesley, M. J. and Thompson, R. N.
Aedes aegypti spread pathogens affecting humans, including dengue, Zika, and yellow fever viruses. Anthropogenic climate change is altering the spatial distribution of Ae aegypti and therefore the locations at risk of vector-borne disease. In addition to climate change, natural climate variability, resulting from internal atmospheric processes and interactions between climate system components (eg, atmosphere–land and atmosphere–ocean interactions), determines climate outcomes. However, the role of natural climate variability in modifying the effects of anthropogenic climate change on future environmental suitability for Ae aegypti has not been assessed fully. In this study, we aim to assess uncertainty arising from natural climate variability in projections of Ae aegypti suitability up to the year 2100. Lancet Planetary Health. December 2024
The time between symptom onset and various clinical outcomes : a statistical analysis of MERS-CoV patients in Saudi Arabia
Althobaity, Yehya, Alkhudaydi, Muhammad, Hill, Edward M., Thompson, Robin N. and Tildesley, Michael J
In this study, we investigate the impact of demographic characteristics on MERS-CoV cases in Saudi Arabia, specifically focusing on the time intervals between symptom onset and key events such as hospitalization, case confirmation, reporting and death. Importantly, we observe age-based differences in the risk of hospitalization and other measures of infection severity, including the probability of death conditional on hospitalization. Careful quantification of epidemiological characteristics, including inference of key epidemiological periods and assessments of differences between cases of different ages, plays a crucial role in understanding the progression of MERS-CoV outbreaks and formulating effective public health strategies to mitigate their impact.
Identification of a terpene synthase arsenal using long-read sequencing and genome assembly of Aspergillus wentii
Richard Olumakaiye, Christophe Corre, Fabrizio Alberti
Fungi are talented producers of secondary metabolites with applications in the pharmaceutical and agrochemical sectors. Aspergillus wentii CBS 141173 has gathered research interest due to its ability to produce high-value norditerpenoid compounds, including anticancer molecules. In this study, we aimed to expand the genomic information available for A. wentii to facilitate the identification of terpenoid biosynthetic genes that may be involved in the production of bioactive molecules.
The results provide a scaffold for the future exploration of terpenoid biosynthetic pathways for bioactive molecules in A. wentii. The terpenoid clusters identified in this study are candidates for heterologous gene expression and/or gene disruption experiments. The description and availability of the long-read genome assembly of A. wentii CBS 141173 further provides the basis for downstream genome analysis and biotechnological exploitation of this species.
Transcription factor deformed wings is an Atg8a-Interacting protein that regulates autophagy
Kołodziej, Marta, Tsapras, Panagiotis, Cameron, Alexander and Nezis, Ioannis P
LC3 (microtubule-associated protein 1 light chain 3, called Atg8 in yeast and Drosophila) is one of the most well-studied autophagy-related proteins. LC3 controls the selectivity of autophagic degradation by interacting with LIR (LC3-interacting region) motifs also known as AIM (Atg8-interacting motifs) on selective autophagy receptors that carry cargo for degradation. Although the function of Atg8 family proteins is primarily cytoplasmic, they are also enriched in the nucleus. Here, we used yeast two-hybrid screening, and we identified transcription factor Deformed wings (Dwg) as an Atg8a-interacting protein in Drosophila. Dwg-Atg8a interaction is LIR motif-dependent. We have created Dwg Y129A/I132A LIR mutant flies and shown that they exhibit elevated autophagy, improved resistance to oxidative stress, and starvation. Our results provide novel insights into the transcriptional regulation of autophagy in Drosophila.
Understanding the ecological versatility of Tetracladium species in temperate forest soils
Anna Lazar, Richard P Phillips, Stephanie Kivlin, Gary D Bending, Ryan M Mushinski
Although Tetracladium species have traditionally been studied as aquatic saprotrophs, the growing number of metagenomic and metabarcoding reports detecting them in soil environments raises important questions about their ecological adaptability and versatility. We investigated the factors associated with the relative abundance, diversity and ecological dynamics of Tetracladium in temperate forest soils. Collectively, our findings highlight the ecological significance of Tetracladium in temperate forest soils and emphasize the importance of site-specific factors and microbial interactions in shaping their distribution patterns and ecological dynamics.
Gladiolin produced by pathogenic Burkholderia synergizes with amphotericin B through membrane lipid rearrangements
Claudia Simm, Tzong-Hsien Lee, Harshini Weerasinghe, Dean Walsh, Ioanna T Nakou, Madhu Shankar, Wai Chung Tse, Rebecca Inman, Robert J Mulder, Freya Harrison, Marie-Isabel Aguilar, Gregory L Challis, Ana Traven
Amphotericin B (AmpB) is an effective but toxic antifungal drug.. AmpB disrupts fungal membranes by two proposed mechanisms: ergosterol sequestration from the membrane and pore formation. Whether these two mechanisms operate in conjunction and how they could be potentiated remains to be fully understood. Here, we report that gladiolin, a polyketide antibiotic produced by Burkholderia gladioli, is a strong potentiator of AmpB and acts synergistically against Cryptococcus and Candida species, including drug-resistant C. auris. Gladiolin also synergizes with AmpB against drug-resistant fungal biofilms, while exerting no mammalian cytotoxicity.. Collectively, our findings shed light on AmpB’s mechanism of action and characterize gladiolin as an AmpB potentiator, showing an antifungal mechanism distinct from its proposed antibiotic activity. We shed light on the synergistic mechanism at the membrane, and provide insights into potentiation strategies to improve AmpB’s activity/toxicity relationship.
Membrane staining and phospholipid tracking in Pseudomonas aeruginosa PAO1 using the phosphatidylcholine mimic propargyl-choline
Chris L B Graham, Jack Bryant, David I Roper, Manuel Banzhaf
Here we describe a method for in vivo phospholipid labelling by fluorescent imaging in Pseudomonas aeruginosa using a phosphatidylcholine (PC) mimic, “propargyl-choline”(PCho). This click-chemistry liable headgroup mimic is visible by microscopy and allows the covalent labelling of lipids. Fluorescence of the cell membranes, visible in heterogenous patches, is dependent on PCho concentration and is localised in the membrane fraction of cells, demonstrating that it is suitable for membrane labelling and cell imaging.