David W. Niesel, PhD

Streptococcus pneumoniaeis a leading cause of community-acquired pneumonia, bacterial meningitis, and otitis media. Our understanding of pneumococcal pathogenesis remains fragmentary. It is generally believed that the identification and characterization of genes whose expression is enhanced in vivo will provide new insights into the mechanisms underlying bacterial pathogenesis and may point to new vaccine or pharmacological targets. We have established two in vivo culture models: the murine peritoneal culture and a murine bacteremic culture model to investigate in vivo gene expression. Using these models, we are assessing the expression of virulence genes/proteins and functional assays for virulence factors/properties. The goal of this work is to document and characterize S. pneumoniae, gene or protein expression differences, or differences in virulence properties, which occur during animal infection.

We are also investigating changes to the S. pneumoniae proteome and global transcriptional activity after extended passage in the laboratory. Passage on laboratory media has been shown to attenuate the virulence of some bacterial pathogens; however the mechanism of this attenuation is unknown. Recent experiments have demonstrated extensive changes to the proteome and global transcriptional gene profiles after 50, 100 and 150 passages on blood agar plates. Significantly, the virulence activity of passage strains is also altered. Current experimentation is focused on identifying the basis of virulence attenuation on the gene and protein expression level after passage. This could lead to a better understanding of virulence and the development of new vaccines and therapeutics for this pathogen.

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