Dissecting the essential role of luxS-relevant small RNAs in biofilm formation of Streptococcus mutans

Transcriptome analysis revealed that several genes related to carbohydrate utilization were differentially expressed, with ccpA being markedly upregulated in both SmqsR2 and SmqsR4 overexpression strains. Specifically, SmqsRs promoted ccpA transcript, and CcpA triggered transcription of SmqsR2 and SmqsR4 via direct binding, thus forming a positive feedback loop. We speculate that SmqsRs augment LuxS-mediated biofilm matrix production, most likely through the activation of gtfB/C/D expression and the reprogramming of S. mutans central carbon metabolism by ccpA.

In summary, we have confirmed that SmqsR2 and SmqsR4 function as supporting factors that maintain the optimal status of the LuxS/AI-2 system in S. mutans, which is important for cell growth, EPS synthesis, and biofilm formation. Hence, sRNA activity may represent a promising target to modulate S. mutans cariogenicity.