My research interests span for the physiology of bacterial pathogens during infection, work on bacterial genetics/genomics and antimicrobial drug resistance. My main area of research interest is the discovery of specific details in the interaction of pathogenic bacteria with the host that could lead to new treatment options and the analysis of antimicrobial resistance determinants. I address the study of bacterial virulence mechanisms, by use of genomic tools, the exploration of microbial physiology, and the detailed analysis of events occurring in experimental infection models. Main scope of this work is the recognition of specific phases characterising microbial physiology during infection with the aim of identification of novel drug targets.
In this context I have focused in the bacterium Streptococcus pneumoniae where I have discovered a novel phase variable methylation mechanism with an epigenetic impact on bacterial phenotypes. This work on epigenetic gene regulation, an aspect which is understudied in prokaryotic biology, is yielding very exciting and novel data showing how methylation of DNA can influence bacterial gene expression.
More recently I have described that pneumococci are capable of replicating in a subset of splenic macrophages prior starting invasive disease in mice and that invasive disease can be prevented by blocking this intracellular replication (Ercoli et al., Nature Microbiology 2018). In order to explore the validity of these findings an ex vivo perfusion model for porcine spleens was developed and intracellular replication of pneumococci in the same subset of splenic macrophages could be confirmed (Chung et al., ALTEX 2019). Most recently MRO was awarded as Chief Investigator by the Health Research Authority a clinical trial to use human spleens in ex vivo perfusion models. This work is now providing the first functional analysis of the roles of specific macrophage subsets in the human spleen during the first phases of infection. This innovative work holds promise to rewrite some of the concepts of the pathogenesis of infection and the rational for antimicrobial drug treatment.
Additional interests include investigation into the molecular determinants of antimicrobial drug resistance, biocide resistance and mechanisms governing mobile genetic elements. This work includes genetic and genomic and description in many bacterial species including the Gram positive Enterococcus faecalis, Listeria monocytogenes, Streptococcus pneumoniae, Staphylococcus aureus, Staphylococcus epidermidis and Clostridium difficile and the Gram negative bacteria Klebsiella pneumoniae, Bacteroides fragilis, Neisseria meningitidis, Escherichia coli, Pseudomonas aeruginosa, Moraxella catarrhalis, and Acinetobacter baumannii.
