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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