general instructions of menadione

Menadione and heme auxotrophic strains were the two most common SCV phenotypes. It has been reported that point mutations in the menadione biosynthetic genes menB, menC, menE, and menF of menadione auxotrophic SCV favor SCV formation. Mutations menadione included bp deletions from nucleotides 55 to 63, frameshift mutations that induce a premature stop codon at position 230, and point mutations (eg, substitution of Gly to Val amino acid at codon 233 in menB). Complementation of mutant alleles of these menadione biosynthetic genes restored wild-type colony morphology and growth characteristics of cultures, and also enhanced virulence in mice.
The common auxotrophs commonly observed in SCV are based on two main mechanisms: (1) defects in electron transport (menadione and heme auxotrophs); (2) defects in thymidylate biosynthesis (thymidine-dependent SCV). Altered hemin biosynthesis is due to mutations in biosynthetic genes (such as hemB) that are associated with reduced phagocytosis, slowed extracellular growth, and abrogated vancomycin bactericidal effect. Similarly, thymidine dependence in clinical S. aureus SCV may be due to non-synonymous point mutations or deletions in thyA, the gene encoding thymidylate synthase. Of particular interest for pharmacological targeting of auxotrophic SCVs, a recent study demonstrated that a metabolic signature of central carbon metabolism is commonly found in SCVs regardless of their auxotrophy. Of note, the study was designed to evaluate clinically relevant thymidine, menadione, and heme auxotrophs of SCV, non-auxotrophic mutants exhibiting SCV phenotypes, and corresponding parental strains (normal phenotypes). all possible metabolic differences. 37 Notably, fractions of (13)C2-aspartate and glutamate and absence of (13)C3-glutamate were observed in all SCVs, indicating reduced carbon flux through the TCA cycle. Likewise, the gene acnA encoding the TCA cycle key enzyme aconitase was downregulated in all investigated SCV phenotypes. These findings strongly suggest that TCA cycle targeting is a good target for SCV eradication despite the SCV genetic background.
Other metabolic changes commonly observed in the SCV phenotype include (1) downregulation of many S. aureus active metabolic genes, such as the α-hemolysin gene (hlY) and coagulase gene (coa), and the effect of staphylococcal Agr Molecular quorum sensing system RNAIII (controls bacterial virulence); (2) Upregulation of genes involved in glycolysis and arginine deiminase pathways, as well as capsule biosynthesis.

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