Latest Publications
Metabolic profiling and antibacterial activity of tree wood extracts obtained under variable extraction conditions
Diana Vinchira-Villarraga, Sabrine Dhaouadi, Vanja Milenkovic, Jiaqi Wei, Emily R. Grace, Katherine G. Hinton, Amy J. Webster, Andrea Vadillo-Dieguez, Sophie E. Powell, Naina Korotania, Leonardo Castellanos, Freddy A. Ramos, Richard J. Harrison, Mojgan Rabiey & Robert W. Jackson
This study aimed to develop a methodological approach to obtain extracts from different tree species with the highest reproducibility and chemical diversity possible, to ensure proper coverage of the trees’ metabolome. Each tree species has a unique metabolic profile, which means that no single protocol is universally effective. Extraction at 50 °C for three cycles using 80% methanol or chloroform/methanol/water showed the best results and is suggested for studying wood metabolome. These observations highlight the need to tailor extraction protocols to each tree species to ensure comprehensive metabolome coverage for metabolic profiling.
Delivery determinants of an Acinetobacter baumannii type VI secretion system bifunctional peptidoglycan hydrolase
Valeriya Bezkorovayna, Brooke K. Hayes, Francesca N. Gillett, Amy Wright, David I. Roper, Marina Harper, Sheena McGowan, John D. Boyce
Acinetobacter baumannii is a Gram-negative opportunistic pathogen and is a common cause of nosocomial infections.). Here we define the regions of interaction between Tae17 and its cognate delivery protein VgrG17 and identify that amino acids G1069 and W1075 in VgrG17 are essential for Tae17 delivery via the T6SS, the first time such specific delivery determinants of T6SS cargo effectors have been defined. Furthermore, we determine that the Tae17 effector is a multidomain, bifunctional, peptidoglycan-degrading enzyme that has both amidase activity, which targets the sugar-peptide bonds, and lytic transglycosylase activity, which targets the peptidoglycan sugar backbone. Moreover, we show that the Tae17 transglycosylase activity is more important than amidase activity for the killing of Escherichia coli. This study provides molecular insight into how the T6SS allows A. baumannii strains to gain dominance in polymicrobial communities and thus improve their chances of survival and transmission.
Characterisation of Itersonilia spp. from Parsnip and Other Hosts
Lauren HK Chappell, Guy C Barker, John P Clarkson
Parsnips (Pastinaca sativa) are a speciality UK crop with an economic value of at least 31M GBP annually. Currently, the major constraints to production are losses associated with root canker disease due to a range of fungal pathogens, among which Itersonilia pastinacae is of most concern to growers. With limited research conducted on this species, this work aimed to provide a much-needed characterisation of isolates from across the UK, continental Europe, and New Zealand. Following whole genome sequencing, specific primers were designed for the molecular characterisation of the isolates using six housekeeping genes and three highly variable functional genes. Phylogenetic analysis separated isolates into two and six clades, respectively, but the grouping was not associated with hosts or locations. Based on the results of this research, there was no evidence to support more than a single species of Itersonilia among the isolates studied.
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.