Cao Yanfan, Zeng Yu, Yang Yuze, Gan Guowu, Chen Shuai, Huang Xiaojing
Fujian Key Laboratory of Oral Diseases and Fujian Provincial Engineering Research Center of Oral Biomaterial and Clinical Research Center for Oral Tissue Deficiency Diseases of Fujian Province, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China.
Front Microbiol. 2025 Jul 31;16:1612841. doi: 10.3389/fmicb.2025.1612841. eCollection 2025.
This study elucidated the critical role of the gene in the () two-component signal (TCS) transduction system during cross-kingdom interactions with (). This gene governs the cariogenic potential of dual-species biofilms.
Gene expression analysis of cocultured samples was performed. The survival rate during HO treatment in single and dual-species was assessed. Bacterial adhesion, extracellular polysaccharide (EPS) synthesis, acidic metabolite accumulation, and early adhesion of in dual-species biofilms were evaluated.
Compared with the wild-type () and complemented strains (liaS-comp), liaS- exhibited impaired acid tolerance due to downregulated comDE expression. The knockout mutant strain also presented reduced expression, leading to diminished glucosyltransferase (Gtf)-mediated bacterial adhesion, EPS synthesis, and acidic metabolite accumulation. Although alleviated oxidative stress by secreting superoxide dismutase, liaS- markedly compromised the intracellular reactive oxygen species (ROS) scavenging capacity and reduced the survival rate during HO treatment in single and dual-species. Furthermore, liaS- inactivation suppressed the early adhesion of in dual-species biofilms by reducing the synthesis of cyclic adenosine monophosphate (cAMP).
This work provides the first evidence that orchestrates a multidimensional phenotypic regulatory network that coordinately modulates biofilm architecture and metabolic activity. This activity ultimately attenuates cariogenicity , thus highlighting liaS as a pivotal virulence determinant in cross-kingdom infections and emphasizing its potential as a therapeutic target against dental caries.
本研究阐明了该基因在与()进行跨界相互作用期间,在()双组分信号(TCS)转导系统中的关键作用。该基因控制着双物种生物膜的致龋潜力。
对共培养样本进行基因表达分析。评估了单物种和双物种在过氧化氢处理期间的存活率。对双物种生物膜中的细菌黏附、胞外多糖(EPS)合成、酸性代谢产物积累以及()的早期黏附进行了评估。
与野生型()和互补菌株(liaS-comp)相比,liaS-由于comDE表达下调而表现出耐酸性受损。liaS基因敲除突变株还呈现出()表达降低,导致葡糖基转移酶(Gtf)介导的细菌黏附、EPS合成和酸性代谢产物积累减少。尽管()通过分泌超氧化物歧化酶减轻了氧化应激,但liaS-显著损害了细胞内活性氧(ROS)清除能力,并降低了单物种和双物种在过氧化氢处理期间的存活率。此外,liaS-失活通过减少环磷酸腺苷(cAMP)的合成抑制了()在双物种生物膜中的早期黏附。
本研究首次证明()精心编排了一个多维表型调控网络,该网络协调调节生物膜结构和代谢活性。这种活性最终减弱了()的致龋性,从而突出了liaS作为跨界感染中关键毒力决定因素的地位,并强调了其作为抗龋齿治疗靶点的潜力。