Gene regulatory mechanisms of metabolic adaptation in Neisseria meningitidis in ex vivo infection models

• Applicant: Professor Dr. Christoph Schoen
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms
• Term: from 2011 to 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 201416097

Neisseria meningitidis usually lives as a commensal bacterium in the upper airways of humans but occasionally can also cause life threatening diseases such as sepsis and acute bacterial meningitis. The genetic basis of meningococcal virulence is still enigmatic, and so far comparative genomics has failed to identify a classical virulence gene set in N. meningitidis. However, recent whole-transcriptome comparisons of a carriage and an invasive strain under in vivo mimicking conditions revealed large differences in the regulation of numerous metabolic genes from the meningococcal core genome. In particular, meningococcal survival in whole blood which is crucial for causing invasive diseases seems to be linked to the bacterial metabolic status via the stringent response. We also found evidence for a cross-talk between the stringent response pathway and other signalling networks including the sigma- E and the MisR regulons. From these data a new picture is emerging where metabolism is closely linked to meningococcal virulence, and genetic factors of metabolic regulation might therefore comprise a novel class of meningococcal virulence-associated genes. Accordingly, in this project we will (i) analyse the meningococcal stringent response pathway and its contribution to blood stream survival of bacterial cells, and (ii) characterize the regulons found to be differentially regulated under ex vivo conditions in a carriage and an invasive strain.

• DFG Programme: Priority Programmes
• Subproject of: SPP 1316: Host-adapted Metabolism of Bacterial Pathogens