Metabolic crosstalk regulates Porphyromonas gingivalis colonization and virulence during oral polymicrobial infection

Nat Microbiol. 2017 Nov;2(11):1493-1499. doi: 10.1038/s41564-017-0021-6. Epub 2017 Sep 18.

Abstract

Many human infections are polymicrobial in origin, and interactions among community inhabitants shape colonization patterns and pathogenic potential 1 . Periodontitis, which is the sixth most prevalent infectious disease worldwide 2 , ensues from the action of dysbiotic polymicrobial communities 3 . The keystone pathogen Porphyromonas gingivalis and the accessory pathogen Streptococcus gordonii interact to form communities in vitro and exhibit increased fitness in vivo 3,4 . The mechanistic basis of this polymicrobial synergy, however, has not been fully elucidated. Here we show that streptococcal 4-aminobenzoate/para-amino benzoic acid (pABA) is required for maximal accumulation of P. gingivalis in dual-species communities. Metabolomic and proteomic data showed that exogenous pABA is used for folate biosynthesis, and leads to decreased stress and elevated expression of fimbrial adhesins. Moreover, pABA increased the colonization and survival of P. gingivalis in a murine oral infection model. However, pABA also caused a reduction in virulence in vivo and suppressed extracellular polysaccharide production by P. gingivalis. Collectively, these data reveal a multidimensional aspect to P. gingivalis-S. gordonii interactions and establish pABA as a critical cue produced by a partner species that enhances the fitness of P. gingivalis while diminishing its virulence.

MeSH terms

  • 4-Aminobenzoic Acid / metabolism
  • 4-Aminobenzoic Acid / pharmacology
  • Adhesins, Bacterial / metabolism
  • Animals
  • Bacterial Adhesion
  • Bacteroidaceae Infections / microbiology*
  • Biofilms
  • Coinfection / metabolism
  • Coinfection / microbiology*
  • Disease Models, Animal
  • Dysbiosis
  • Female
  • Humans
  • Metabolomics
  • Mice
  • Mice, Inbred BALB C
  • Microbial Interactions*
  • Periodontitis / microbiology
  • Porphyromonas gingivalis / drug effects
  • Porphyromonas gingivalis / growth & development
  • Porphyromonas gingivalis / metabolism*
  • Porphyromonas gingivalis / pathogenicity*
  • Proteomics
  • Streptococcal Infections / microbiology*
  • Streptococcus gordonii / drug effects
  • Streptococcus gordonii / genetics
  • Streptococcus gordonii / metabolism*
  • Streptococcus gordonii / pathogenicity
  • Virulence
  • para-Aminobenzoates / metabolism
  • para-Aminobenzoates / pharmacology

Substances

  • Adhesins, Bacterial
  • para-Aminobenzoates
  • 4-Aminobenzoic Acid