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New insights into the landscape relationships of host response to bacterial pathogens

Modern understanding of microbiology largely lays foundation in the biological characterization of microorganisms. However, the landscape relationships of host transcriptional response (HTR) to different bacterial pathogens have not yet been systematically explored. Here, we established the first generation of HTR network (HTRN) according to the HTR similarities among 21 different human pathogenic bacterial species by integrating 258 pairs of host cellular gene expression profiles upon infections. Further, the network was dissected into five bacterial communities of more consensus internal HTR. Interestingly, analysis of signature genes across different communities revealed that distinct community signatures (CS) present differential gene expression patterns. Functional annotation suggested a common feature of host cell response to bacterial infections that specific functional gene clusters (BPs and/or signaling pathways) were preferentially elicited or subverted by community bacterial pathogens. Notably, community signatures (especially key associators participating dissimilar functional profiles) were highly enriched of GWAS disease-related genes, which associated bacterial infections with common and specific non-infectious human disease(s). About 40% of the associations were confirmed by literature investigation that further indicated possible/potential association directionality. Our characterization and analysis were the first to feature differential community HTRs upon bacterial pathogen infections and suggested new perspective of understanding infection-disease associations and underlying pathogenesis.