Mechanisms of folate metabolism-related substances affecting Staphylococcus aureus infection

Qiyuan Jin1, Xiaolu Xie1, Yaxuan Zhai1

  • 1Department of Clinical Laboratory, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Insights

Staphylococcus aureus can survive inside host cells, and its intracellular infection is linked to folate metabolism. Understanding these mechanisms offers new insights into S. aureus pathogenesis and potential therapeutic targets.

Area of Science:

  • Microbiology
  • Molecular Pathogenesis
  • Bacterial Physiology

Background:

  • Staphylococcus aureus is a significant clinical pathogen causing diverse infections.
  • While typically extracellular, S. aureus exhibits intracellular survival capabilities.
  • Folate metabolism is increasingly recognized as crucial for S. aureus intracellular infections.

Purpose of the Study:

  • To review the mechanisms of folate metabolism impacting S. aureus infection.
  • To explore the role of related substances in S. aureus pathogenesis.
  • To provide insights into the molecular basis of S. aureus intracellular survival.

Main Methods:

  • Literature review of studies on S. aureus folate metabolism and intracellular infection.
  • Analysis of molecular mechanisms involving folate pathway enzymes and deficiencies.
  • Examination of antibiotic effects on S. aureus folate metabolism and virulence.

Main Results:

  • Deficiency in pabA leads to loss of tetrahydrofolic acid (THF)-dependent dTMP, inhibiting nucleotide synthesis.
  • The antibiotic trimethoprim-sulfamethoxazole (TMP/SMX) disrupts folate metabolism, inducing thymidine-dependent small-colony variants (TD-SCVs).
  • Serine hydroxymethyltransferase (SHMT) confers resistance to lysostaphin in S. aureus.

Conclusions:

  • Folate metabolism is a critical factor in S. aureus intracellular pathogenesis.
  • Targeting folate pathways or related mechanisms may offer novel therapeutic strategies.
  • Understanding these pathways enhances knowledge of S. aureus virulence and resistance.

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