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One-carbon metabolism and microbial pathogenicity.

Kendall S Stocke1, Richard J Lamont1

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One-carbon metabolism (OCM) is crucial for microbial biosynthesis and virulence. This study reveals how Porphyromonas gingivalis uniquely responds to para-aminobenzoic acid (pABA) levels, impacting pathogenicity and host interactions.

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Area of Science:

  • Microbiology
  • Biochemistry
  • Molecular Biology

Background:

  • One-carbon metabolism (OCM) pathways generate essential biomolecule precursors.
  • Folates, synthesized via OCM, are vital for human health and microbial processes.
  • OCM influences microbial virulence, often through para-aminobenzoic acid (pABA) availability.

Purpose of the Study:

  • To investigate the role of OCM and pABA in Porphyromonas gingivalis pathogenicity.
  • To explore the differential responses of P. gingivalis to pABA compared to other microbes.
  • To understand the interplay between OCM, protein synthesis, and host-microbe dynamics.

Main Methods:

  • Analysis of OCM pathways and their intermediates.
  • Investigating the impact of pABA availability on P. gingivalis virulence.
  • Examining the role of alarmones ZMP and ZTP in folate homeostasis.
  • Studying heterotypic microbial communities involving P. gingivalis.

Main Results:

  • P. gingivalis exhibits increased pathogenicity with lower pABA levels, contrasting typical microbial responses.
  • Exogenous pABA can modulate the behavior of P. gingivalis in mixed microbial communities.
  • OCM links protein translation regulation to adaptive responses to folate levels via alarmones ZMP and ZTP.

Conclusions:

  • OCM plays a complex role in microbial virulence, with P. gingivalis showing unique pABA-dependent pathogenicity.
  • Understanding these OCM dynamics offers insights into host-microbe interactions and potential therapeutic targets.