Biology subjects

Dawson, L.

Publications and source records attributed to Dawson, L..

3 recordsLinked to original sources

bioRxiv2026

A panel of genotypically and phenotypically characterised WHO priority Gram-negative bacteria to facilitate antimicrobial and diagnostic development

Background Antimicrobial-resistant Gram-negative bacteria pose a major threat to global health. In the WHO Bacterial Priority Pathogen List (BPPL) 2024, several species were classified as critical or high priority for research and development of new antimicrobial therapeutics and diagnostics. However, access to well-characterised and clinically relevant bacterial isolate panels remains an unmet need for development and validation. Methods We constructed five panels of Gram-negative bacterial isolates, cultured from samples originally referred to the UK Health Security Agency Antimicrobial Resistance and Healthcare-Associated Infections Reference Unit for analysis between 2014 and 2025. For each isolate, antimicrobial susceptibilities were determined against a range of clinically relevant antibiotics, including third-generation cephalosporins, carbapenems, colistin and other last-line antibiotics. WGS was performed on all isolates, and previously described resistance determinants were characterised. Results The five panels consist of 145 isolates and represent 81 sequence types across Escherichia coli (30 isolates), Klebsiella pneumoniae (30 isolates), carbapenem-resistant Acinetobacter baumannii (30 isolates), carbapenem-resistant Pseudomonas aeruginosa (30 isolates), and a mixed panel of other healthcare-associated Enterobacterales species (25 isolates). Panels are highly representative of globally relevant strains, including those currently in circulation and on the WHO BPPL 2024, and of resistance mechanisms of public health importance. Conclusion The panels provide a diverse, comprehensive set of multidrug-resistant Gram-negative bacterial isolates, representative of strains currently in circulation globally. Selected isolates carry a breadth of important resistance mechanisms and are highly relevant to the current epidemiological landscape. The isolates and associated metadata are available to industry, academia, and other laboratories for use in developing novel antimicrobial compounds and diagnostic assays.

microbiology↗

bioRxiv2024

Mechanical activation of VE-cadherin stimulates AMPK to increase endothelial cell metabolism and vasodilation

Endothelia cells respond to mechanical force by stimulating cellular signaling, but how these pathways are linked to elevations in cell metabolism and whether metabolism supports the mechanical response remains poorly understood. Here, we show that application of force to VE-cadherin stimulates liver kinase B1 (LKB1) to activate AMP-activated protein kinase (AMPK), a master regulator of energy homeostasis. VE-cadherin stimulated AMPK increases eNOS activity and localization to the plasma membrane as well as reinforcement of the actin cytoskeleton and cadherin adhesion complex, and glucose uptake. We present evidence for the increase in metabolism being necessary to fortify the adhesion complex, actin cytoskeleton, and cellular alignment. Together these data extend the paradigm for how mechanotransduction and metabolism are linked to include a connection to vasodilation, thereby providing new insight into how diseases involving contractile, metabolic, and vasodilatory disturbances arise.

cell biology↗

bioRxiv2017

Macrophages are required to coordinate mouse digit tip regeneration

In mammals, macrophages are known to play a major role in tissue regeneration. These cells contribute to inflammation, histolysis, re-epithelialization, re-vascularization and cell proliferation. While macrophages have been shown to be essential for epimorphic regeneration in salamanders and fish, their role has not been elucidated in mammalian epimorphic regeneration. Here, using the mouse digit tip model as a mammalian model of epimorphic regeneration, we demonstrate that macrophages are essential for the regeneration process. Using cell depletion strategies, we show that regeneration is completely inhibited; bone histolysis does not occur, wound re-epithelization is inhibited and the blastema does not form. Rescue of epidermal wound closure, in the absence of macrophages, promotes blastema accumulation but not differentiation indicating that macrophage play a role in re-differentiation. Additionally, inhibition of osteoclasts and the degradation process is not sufficient to inhibit regeneration. These findings show that macrophages play an essential role in coordinating the epimorphic regenerative response in mammals.

developmental biology↗