Lias From Two-Component System Is Essential For Caries

This study aimed to investigate the role of the liaS in Streptococcus mutans during cross-kingdom interactions with Candida albicans, focusing on its regulatory effects on cariogenic potential. S. mutans 593, liaS⁻, and liaS⁻-comp were compared. Gene expression was analyzed via RT-PCR. Functional assays assessed acid tolerance, glucosyltransferase (Gtfs)-mediated adhesion, extracellular polysaccharide (EPS) synthesis, reactive oxygen species (ROS) scavenging capacity, and survival. The impact of liaS on C. albicans signaling pathways (Ras1-cAMP-Efg1) was evaluated by measuring cAMP contents and hyphal development. Dual-species biofilm cariogenicity was validated in an in vivo model. 1.liaS⁻ impaired acid tolerance via downregulated comDE and reduced vicRK expression, diminishing Gtfs-mediated adhesion, EPS production, and acid accumulation. 2.Despite C. albicans secreting superoxide dismutase to mitigate oxidative stress, liaS⁻ compromised intracellular ROS scavenging, reducing survival under H2O2 stress. liaS inactivation suppressed C. albicans cAMP synthesis, downregulating the Ras1-cAMP-Efg1 pathway and weakening fungal adhesion and hyphal growth in dual-species biofilms. In vivo, liaS⁻ attenuated biofilm cariogenicity, highlighting its role in virulence regulation. The liaS coordinates a multidimensional network regulating dual-species cross-kingdom interactions, influencing biofilm virulence through acid tolerance, EPS synthesis, ROS scavenging, and fungal signaling. As a pivotal virulence determinant, liaS represents a promising therapeutic target for disrupting cariogenic biofilms and combating dental caries.