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. 2026 Mar 31;11(4):e00668-25. doi: 10.1128/msphere.00668-25

Fig 1.

Metabolic network showing how carbon sources regulate GAS virulence. Traces pathways from sucrose, maltose and GlcNAc through glycolysis with metabolic intermediates signaling to global regulators controlling virulence factors.

The central metabolic decision-making network of GAS links carbon source availability to virulence expression. Carbon sources depicted include sucrose (Suc), maltose (Mal), lactose (Lac), N-acetylglucosamine (GlcNAc), galactose (Gal), and sialic acid (Sia). Environmental and nutrient cues shape carbon flux through core pathways, including glycolysis, homolactic fermentation (LDH), and mixed-acid fermentation (PDH/PFL), which together define GAS core metabolism. Under nutrient-limited conditions, metabolic flux is reprogrammed to promote amino acid catabolism (e.g., the ADI pathway) and to downregulate fatty acid biosynthesis. Metabolic intermediates and end-products function as signaling molecules that modulate the activity of global regulators (indicated in magenta), thereby coupling metabolic state to transcriptional control. These regulators directly govern the expression of key virulence determinants, including the hyaluronic acid capsule, exotoxins (SpeA, SpeB), and other immunomodulatory effectors, coordinating virulence programs with metabolic capacity and environmental adaptation. Dotted arrows indicate pathways not depicted in detail. Created with BioRender.com.