Open to: Norwich Research Park

Abstract: Hypervirulent lineages of Klebsiella pneumoniae (hvKp) are unique in their clinical presentation as they cause bacteraemic hepatic abscesses. In addition, K2 ST25 strains are responsible for invasive disease in pigs. We have recently shown that intracellular replication of Streptococcus pneumoniae precedes the onset of bacteraemia. We aimed to test the hypothesis that Kp abscess formation starts after within macrophage replication. Using thirteen isolates representative of both hypervirulent and multidrug resistant lineages in murine infection models we showed that intracellular replication within hepatic tissue macrophages followed by release of neutrophil-resistant bacterial clusters correlated with the capacity to form abscesses. Bacterial blood counts or the capacity to survive within macrophages did not correlate with hvKp phenotype. Data in mice were confirmed in the translational model of porcine organ ex vivo co-perfusion of liver and spleen. Our data indicate that the efficient replication of hvKp isolates within tissue macrophages is the most likely mechanism for the origin of hvKp hepatic abscesses which characterise human disease.

Biography:  Prof. Marco Rinaldo Oggioni is an expert in bacterial genetics and pathogenesis of infection. MRO has worked as Consultant Microbiologist for 20 years at the University Hospital in Siena (Italy) and has joined as Professor of Microbial Genetics in 2013 the University of Leicester (UK). 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 treatment options and the analysis of antimicrobial resistance determinants. 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 novel drug targets or correlates of vaccine protection.