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A Tandem Liquid Chromatography–Mass Spectrometry-based Approach for Metabolite Analysis of Staphylococcus aureus
Published on: March 28, 2017
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.
Abstract:
Staphylococcus aureus (S. aureus) is one of the critical clinical pathogens which can cause multiple diseases ranging from skin infections to fatal sepsis. S. aureus is generally considered to be an extracellular pathogen. However, more and more evidence has shown that S. aureus can survive inside various cells. Folate plays an essential role in multiple life activities, including the conversion of serine and glycine, the remethylation of homocysteine to methionine, and the de novo synthesis of purine /dTMP, et al. More and more studies reported that S. aureus intracellular infection requires the involvement of folate metabolism. This review focused on the mechanisms of folate metabolism and related substances affecting S. aureus infection. Loss of tetrahydrofolic acid (THF)-dependent dTMP directly inhibits the nucleotide synthesis pathway of the S. aureus due to pabA deficiency. Besides, trimethoprim-sulfamethoxazole (TMP/SMX), a potent antibiotic that treats S. aureus infections, interferes in the process of the folate mechanism and leads to the production of thymidine-dependent small-colony variants (TD-SCVs). In addition, S. aureus is resistant to lysostaphin in the presence of serine hydroxymethyltransferase (SHMT). We provide new insights for understanding the molecular pathogenesis of S. aureus infection.
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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