Ikeda, E. | Search bioRxiv

bioRxiv2025

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

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.

microbiology↗

bioRxiv2023

Gut microbiota-mediated alleviation of dextran sulfate sodium-induced colitis in mice.

SummaryWe found a disease-resistant BALB/c substrain with lower susceptibility to DSS-induced colitis. Gut microbiota analysis using 16S rRNA analysis observed the expansion of butyrate-producing Roseburia species in mice with decreased susceptibility to the disease. Gut dysbiosis characterized by an imbalanced microbiota is closed involved in the pathogenesis of a widespread gastrointestinal inflammatory disorder, inflammatory bowel disease. However, it is unclear how the complex intestinal microbiota affects resistance to mucosal inflammation. Here, we showed differences in the susceptibility of inbred BALB/c mice from three main distributors of laboratory animals to colitis; clinical symptoms, such as weight loss, disease activity index score, and colon shortening were assessed. Analysis of the gut microbiota using 16S rRNA sequencing revealed clear separation of the gut microbial composition among mice from the vendors. Notably, the abundance of the phylum Actinobacteriota was strongly associated with disease activity. We also observed the expansion of butyrate-producing Roseburia species in mice with decreased susceptibility to the disease. Further cohousing experiments showed that variation in clinical outcomes was more correlated with the gut microbiota than genetic variants among substrains from different suppliers. Targeting butyrate-producing bacteria could have therapeutic potential for ulcerative colitis.

microbiology↗