[Seminar] Intracellular replication of Streptococcus pneumoniae inside splenic macrophages serves as a reservoir for septicaemia

Seminar

Title: Intracellular replication of Streptococcus pneumoniae inside splenic macrophages serves as a reservoir for septicaemia

Speaker: Prof. Marco Rinaldo Oggioni

Affiliation: Professor of Microbial Genetics, Department of Genetics and Genome Biology, University of Leicester

Honorary Consultant Microbiologist, University Hospitals of Leicester, NHS Trust

Abstract

Bacterial septicaemia is a major cause of mortality, but its pathogenesis remains poorly understood. In experimental pneumococcal murine intravenous infection, an initial reduction of bacteria in the blood is followed hours later by a fatal septicaemia. These events represent a population bottleneck driven by efficient clearance of pneumococci by splenic macrophages and neutrophils, but as we show in this study, accompanied by occasional intracellular replication of bacteria that are taken up by a subset of CD169+ splenic macrophages in mice and pigs. In this model, proliferation of these sequestered bacteria provides a reservoir for dissemination of pneumococci into the bloodstream. Intracellular replication of pneumococci within CD169+ splenic macrophages was now observed also during pneumonia in mice and baboons and importantly the prevention of splenic replication of bacteria prevented bacteraemia irrespective of ongoing acute pneumonia. These key events preceding invasive disease are now being translated to humans by monitoring inflation in a model of ex vivo perfusion of human spleens. We hypothesis that these findings will rewrite some aspects of the pathogenesis of invasive infection and possible revise current strategies for treatment and prevention.

Short bio

Prof. Marco Rinaldo Oggioni is an expert in bacterial genetics, pathogenesis of infection and antimicrobial drug resistance. MRO graduated from Medical School in 1990 (University of Verona, Italy) and completed then a Specialisation in Clinical Microbiology (1994, University of Siena, Italy). MRO has worked as Clinical Microbiologist for 20 years at the University Hospital in Siena Italy (1993-2013) where he held also a teaching non-tenure position at the University of Siena. In 2013 MRO has as Professor of Microbial Genetics the University of Leicester and is since 2015 an Honorary Consultant Microbiologist with the University Hospitals of Leicester, NHS Trust. MRO has published over 115 articles.

MRO has two main areas of research interest which are the discovery of specific details in the interaction of pathogenic bacteria with the host that could lead to new options for treatment or prevention of infection. MRO addresses 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 targets for intervention. In this context MRO has focused in the bacterium Streptococcus pneumoniae on carbon metabolism, discovered a novel phase variable methylation mechanism with an epigenetic impact on bacterial phenotypes and most recently the ability of bacteria to replicate within a subset of host cells early in disease before the onset of bacteraemia leading to sepsis. This discovery of this key aspect in the pathogenesis of invasive bacterial infection and the setup of a model of ex vivo  human spleen perfusion is opening many exciting research questions and projects, some of which possibly leading to revision of current strategies for treatment and prevention.

In addition, MRO has currently projects on phase variation in pneumococci, Listeria, enterococci and Lactobacillus and on mobile genetic elements and drug resistance in staphylococci, Acinetobacter and Pseudomonas.