The quorum sensing peptide BlpC regulates the transcription of genes outside its associated gene cluster and impacts the growth of Streptococcus thermophilus

Authors: McAnulty, Michael; Guron, Giselle; Oest, Adam; Miller, Amanda; Renye, John

Submitted to: Frontiers in Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/8/2023
Publication Date: 1/8/2024
Citation: McAnulty, M.J., Guron, G.P., Oest, A.M., Miller, A.L., Renye Jr, J.A. 2024. The quorum sensing peptide BlpC regulates the transcription of genes outside its associated gene cluster and impacts the growth of Streptococcus thermophilus. Frontiers in Microbiology. https://doi.org/10.3389/fmicb.2023.1304136.
DOI: https://doi.org/10.3389/fmicb.2023.1304136

Interpretive Summary: The yogurt bacterium Streptococcus thermophilus (S. thermophilus) is capable of producing antimicrobial compounds that have potential for use as food preservatives or alternatives to antibiotics. This study demonstrated that the signaling molecule BlpC required to induce production of the antimicrobial can also affect the expression of other genes by S. thermophilus. BlpC was shown to negatively affect the growth of several S. thermophilus strains, possibly explaining why some strains do not produce BlpC and bacteriocin on their own unless BlpC is added to their environment. Results from this study have the potential to identify methods for optimizing the production of natural antimicrobial compounds from dairy cultures to allow for their use in food safety and human/animal health applications.

Technical Abstract: Bacteriocin production in Streptococcus thermophilus is regulated by cell density dependent signaling molecules, including BlpC which regulates transcription from within the bacteriocin-like peptide (blp) gene cluster. In some strains, like S. thermophilus ST106, this signaling system does not function properly, but bacteriocin production can be induced using a synthetic signaling molecule. Transcriptomic analysis was used to compare global gene expression within ST106 in the presence or absence of synthetic BlpC. In addition to the genes involved with bacteriocin production, BlpC affected expression of several transcription regulators outside the blp gene cluster, including a putative YtrA-subfamily transcriptional repressor. In S. thermophilus B59671, thermophilin 110 is encoded within the blp gene cluster and naturally expressed. BlpC regulates expression of thermophilin 110, but also suppresses the production of another bacteriocin, thermophilin 13, and induced the same YtrA-subfamily transcriptional repressor identified in ST106. Additionally, it was shown that the broad-spectrum antimicrobial activity associated with strain B59671 was due to the production of thermophilin 110, while thermophilin 13 appears to be a redundant system for suppressing intraspecies growth. BlpC production was shown to negatively affect the growth of strains B59671, ST106 and LMG18311, further suggesting it may induce or suppress the transcription of genes that are not associated with the production of bacteriocins. Results from this study are expected to assist in defining conditions to optimize the production of bacteriocins for applications in agriculture or human and animal health.