Extensive Adaptive Changes Occur in the Transcriptome of Streptococcus agalactiae (Group B Streptococcus) in Response to Incubation with Human Blood

Abstract

To enhance understanding of how Streptococcus agalactiae (group B streptococcus, GBS) adapts during invasive infection, we performed a whole-genome transcriptome analysis after incubation with whole human blood. Global changes occurred in the GBS transcriptome rapidly in response to blood contact following shift from growth in a rich laboratory medium. Most (83%) of the significantly altered transcripts were down-regulated after 30 minutes of incubation in blood, and all functional categories of genes were abundantly represented. We observed complex dynamic changes in the expression of transcriptional regulators and stress response genes that allow GBS to rapidly adapt to blood. The transcripts of relatively few proven virulence genes were up-regulated during the first 90 minutes. However, a key discovery was that genes encoding proteins involved in interaction with the host coagulation/fibrinolysis system and bacterial-host interactions were rapidly up-regulated. Extensive transcript changes also occurred for genes involved in carbohydrate metabolism, including multi-functional proteins and regulators putatively involved in pathogenesis. Finally, we discovered that an incubation temperature closer to that occurring in patients with severe infection and high fever (40°C) induced additional differences in the GBS transcriptome relative to normal body temperature (37°C). Taken together, the data provide extensive new information about transcriptional adaptation of GBS exposed to human blood, a crucial step during GBS pathogenesis in invasive diseases, and identify many new leads for molecular pathogenesis research.

Leucine-rich Repeats of Bacterial Surface Proteins Serve as Common Pattern Recognition Motifs of Human Scavenger Receptor gp340

“…Expression pattern of differentially interacting surface molecules could also target the bacteria to different host sites. In that context, it is interesting to note that the expression of both Spy0843 and LrrG is increased in vivo during early phases of host-bacteria interaction (40,49,50).…”

Fever temperature enhances mechanisms of survival of Streptococcus agalactiae within human endothelial cells

“…Sudden temperature upshift may induce temporary growth inhibition of bacterial cells and rearrangement of gene expression directed towards survival, including for GBS strains (5,(14)(15)(16). The present study demonstrated that temperature changes may influence GBS survival within endothelial cells.…”

“…Many of these proteins may participate in adherence to host molecules during colonization or invasion. It has been shown previously that there was no significant difference in transcript levels between 30˚C and 40˚C for genes involved in the synthesis of the two known pilin systems in GBS (5). In contrast, several other genes encoding putative cell-surface proteins with an LPXTG/LPXTN cell-wall anchoring motif were differentially expressed according to the temperature.…”

“…Conversely, reduction in the number of intracellular viable bacteria in response to a temperature change from 37˚C to 40˚C was observed 2 h post-infection among serotype V strains. Such results underscore the great complexity of the bacterial stress response induced by growth temperature, with mechanisms involving proteins required during bacterial growth, whereas others are only necessary during a specific step of the growth (5).…”

“…Bacterial incubation at temperatures closer to that occurring in patients with severe infection and high fever (40˚C) induced differences in GBS genes implicated in virulence, as the up-regulation of several transcripts. For example, the genes in the hemolysin operon cyl, CAMP factor (an extracellular cytolytic protein involved in GBS pathogenesis), proteins with LPXTG motifs, chaperones, heat-shock proteins and a heat-inducible transcription regulator were clearly overexpressed at 40˚C (4,5).…”