Understanding Shigella persistent infection and antimicrobial resistance

Shigella is a diarrhoeal pathogen and is responsible for a significant burden worldwide. It has recently emerged that Shigella can establish persistent infections. These infections are not fully cleared by the immune system and cannot be eradicated by antibiotic treatments. Understanding the factors that contribute to Shigella persistent infections and antibiotic tolerance is crucial to inform new disease management and prevention measures. To shed light on the Shigella ability to establish persistent infections and develop tolerance against antibiotics, we study the role of both host and pathogen factors, taking advantage of in vitro models as well as the zebrafish-Shigella in vivo model. This study supports the development of targeted interventions and therapeutic approaches to mitigate the impact of Shigella on human health.

• Understanding Shigella persistent infection and antimicrobial resistance

Phylogenetic and phenotypic characterisation of E. coli from diabetic foot ulcers

Infections of diabetic foot ulcers (DFUs) are a common complication of diabetes, frequently leading to lower-limb amputations. We combine whole genome sequencing (WGS) and laboratory assays to elucidate the diversity of Escherichia coli associated with DFUs. Using WGS data, we aim to reconstruct the phylogenetic tree of DFU-associated Escherichia coli, identify virulence factors, and antibiotic resistance genes. We also aim to characterise phenotypically DFU-associated Escherichia coli isolates by assessing their ability to form biofilms and cause hallmarks of disease in cell and animal models. By integrating genomic and phenotypic data, our research aims to enhance our understanding of E. coli infections in DFUs, ultimately leading to the development of targeted prevention and management strategies. This study has the potential to significantly improve the health and well-being of individuals with diabetes by reducing the incidence of DFU-associated complications and mitigating the need for lower-limb amputations.

• Phylogenetic and phenotypic characterisation of E. coli from diabetic foot ulcers

Use of zebrafish to study the neurotropism of Sindbis virus

Sindbis virus (SINV) is an alphavirus primarily transmitted to vertebrate hosts through mosquito bites. The broad host spectrum of SINV makes it an ideal model for other alphaviruses provoking more severe symptoms in humans, like Chikungunya virus, whose incidence is on the rise in Europe because of climate change. Like other alphaviruses, SINV can cross the blood-brain barrier (BBB) and infect the central nervous system (CNS). However, the exact mechanisms by which alphaviruses breach the BBB, infiltrate the CNS, and impact neuronal function are poorly understood. In this project we established an interdisciplinary collaboration between the Department of Infectious Diseases and the Centre for Developmental Neurobiology. Together we apply the zebrafish model to study the mechanisms of SINV neurotropism and its effects on the CNS. The data obtained will provide valuable insights into SINV pathogenesis and contribute to elucidate the complex interactions of alphaviruses with the host.