Functional dissection of polymicrobial synergy between Porphyromonas gingivalis and Streptococcus gordonii

Whole proteome proteomics data for P. gingivalis in the presence or absence of 4 aminobenzoate/para-amino benzoic acid (pABA)Many human infections are polymicrobial in origin, and synergistic interactions among community inhabitants control colonization and pathogenic potential (Murray et al., 2014). However, few interspecies interactions have been functionally dissected at the molecular level or characterized on a systems level. Periodontitis, which is the sixth most prevalent infectious disease worldwide (Kassebaum et al., 2014), is associated with a dysbiotic microbial community, and the keystone pathogen Porphyromonas gingivalis forms synergistic communities with the accessory pathogen Streptococcus gordonii (Lamont and Hajishengallis, 2015). P. gingivalis and S. gordonii communicate through co-adhesion and metabolite perception, and close association between P. gingivalis and S. gordonii results in significant changes in the expressed proteomes of both organisms (Kuboniwa et al., 2012, Hendrickson et al., 2012). Here we show that streptococcal 4 aminobenzoate/para-amino benzoic acid (pABA) is required for maximal accumulation of P. gingivalis in communities with S. gordonii. Exogenous pABA upregulates production of fimbrial interspecies adhesins and of a tyrosine phosphorylation-dependent signaling system in P. gingivalis. Consequently, fimbrial-dependent attachment and invasion of epithelial cells by P. gingivalis is also increased by pABA. Moreover, trans-omics studies performed by proteomics and metabolomics showed that pABA induces metabolic shifts within P. gingivalis, predominantly folate derivative biosynthesis. In a murine oral infection model, pABA increased colonization and survival of P. gingivalis, but did not increase virulence. The results establish streptococcal pABA as a major component of the interspecies S. gordonii-P. gingivalis interaction which regulates distinct aspects of polymicrobial synergy