Glycerol suppresses lactose-dependent growth of Streptococcus pyogenes through a transcription-independent mechanism

Bando, A.; Hirose, Y.; Bertolla, O. M.; Takemoto, N.; Brouwer, S.; O'Donohue, J.; Ono, M.; Ikeda, E.; Nizet, V.; Walker, M. J.; Kawabata, S.

doi:10.1101/2025.11.24.690200

bioRxiv · 10.1101/2025.11.24.690200

Glycerol suppresses lactose-dependent growth of Streptococcus pyogenes through a transcription-independent mechanism

Bando, A.·Hirose, Y.·Bertolla, O. M.·Takemoto, N.·Brouwer, S.·O'Donohue, J.·Ono, M.·Ikeda, E.·Nizet, V.·Walker, M. J.·Kawabata, S.

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Abstract

Streptococcus pyogenes (group A Streptococcus; GAS) requires flexible metabolic regulation to adapt to diverse host environments; however, its physiological responses to lactose and glycerol remain poorly characterized compared with glucose. In this study, we analyzed three representative serotype M1 GAS strains--the M1global strain 5448, the ancestral M1 strain SF370, and SP1380 as a representative of the recently emerged M1UK lineage. Glycerol consistently suppressed lactose-dependent growth across all strains, while glycerol-dependent respiratory activity was observed in 5448 and SF370 but was absent in SP1380. RNA-seq analysis of strain 5448 revealed no significant transcriptional changes upon glycerol supplementation, indicating that this inhibitory effect likely occurs through a non-transcriptional mechanism. In contrast, lactose supplementation induced distinct transcriptional programs compared with glucose, including coordinated expression changes gene sets regulated by carbohydrate-responsive transcription factors (CcpA, MalR, and NanR) and by the virulence regulator Mga and the stress-response regulator Rgg. Together, these findings identify a previously unrecognized layer of carbon source-dependent metabolic regulation and growth control in GAS.

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Bando, A., Hirose, Y., Bertolla, O. M., Takemoto, N., Brouwer, S., O'Donohue, J., Ono, M., Ikeda, E., Nizet, V., Walker, M. J., Kawabata, S.. 2025-11-24. Glycerol suppresses lactose-dependent growth of Streptococcus pyogenes through a transcription-independent mechanism. https://doi.org/10.1101/2025.11.24.690200

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