Relatively little is understood about the dynamics of global host-pathogen transcriptome changes that occur during
bacterial infection of mucosal surfaces. To test the hypothesis that group A Streptococcus (GAS)
infection of the oropharynx provokes a distinct host transcriptome response, we performed genome-wide transcriptome analysis using a nonhuman primate model of experimental
pharyngitis. We also identified host and pathogen biological processes and individual host and pathogen gene pairs with correlated patterns of expression, suggesting interaction. For this study, 509 host genes and seven
biological pathways were differentially expressed throughout the entire 32-day
infection cycle. GAS
infection produced an initial widespread significant decrease in expression of many host genes, including those involved in
cytokine production, vesicle formation, metabolism, and signal transduction. This repression lasted until day 4, at which time a large increase in expression of host genes was observed, including those involved in protein translation, antigen presentation, and
GTP-mediated signaling. The interactome analysis identified 73 host and pathogen gene pairs with correlated expression levels. We discovered significant correlations between transcripts of GAS genes involved in hyaluronic
capsule production and host endocytic vesicle formation, GAS
GTPases and host fibrinolytic genes, and GAS response to interaction with neutrophils. We also identified a strong signal, suggesting interaction between host gammadelta T cells and genes in the GAS
mevalonic acid synthesis pathway responsible for production of
isopentenyl-pyrophosphate, a short-chain
phospholipid that stimulates these T cells. Taken together, our results are unique in providing a comprehensive understanding of the host-pathogen interactome during mucosal
infection by a bacterial pathogen.