Global transcription profiling and virulence potential of Streptococcus pneumoniae after serial passage

Streptococcus pneumoniae, a facultative human pathogen associated with wide variety of diseases, such as pneumonia, meningitis, sepsis and otitis media. Factors involved in the initial colonization, survival and etiology of this commensal bacteria in the human host from the ex vivo environment is still not clearly understood. Here, we report alterations in global transcriptional profiles of S. pneumoniae 6304 serotype 4 after 50 passages (50P) and 100 passages (100P) on laboratory media to better understand gene expression strategies employed by the bacterium during progression from the nasopharynx to the blood. The results show that six-fold more genes were differentially expressed after 100P as compared to 50P. After 100P on blood agar plates, 726 genes (33%) of 2192 genes in the S. pneumoniae genome were differentially expressed. Moreover, the majority of these genes (68%) were expressed at higher levels with increasing passage number and from different functional groups. Significantly, all the genes present in Region of Diversity 10 (RD10) are required for virulence during blood stream infection showed enhanced expression after passage. However, there was no significant decrease in the LD(50) of serial passage strains compare to single passage strain in a mouse challenge model. Overall, our data suggest that bacteria adapt to extended laboratory passage by substantially altering gene expression. Furthermore, extended passage on blood agar plates reduces the expression of genes associated with initial colonization and adherence but enhances the expression of genes needed for systemic infection.