Hospital of Stomatology, Guanghua School of Stomatology, Sun Yat-sen University, 56 Lingyuanxi Road, Guangzhou, 510055, China.
Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China.
Appl Microbiol Biotechnol. 2024 May 18;108(1):336. doi: 10.1007/s00253-024-13172-9.
To investigate the cell-cell interactions of intergeneric bacterial species, the study detected the survival of Enterococcus faecalis (Ef) under monospecies or coaggregation state with Fusobacterium nucleatum subsp. polymorphum (Fnp) in environmental stress. Ef and Fnp infected the human macrophages with different forms (Ef and Fnp monospecies, Ef-Fnp coaggregates, Ef + Fnp cocultures) for exploring the immunoregulatory effects and the relevant molecular mechanisms. Meanwhile, the transcriptomic profiles of coaggregated Ef and Fnp were analyzed. Ef was shown to coaggregate with Fnp strongly in CAB within 90 min by forming multiplexes clumps. Coaggregation with Fnp reinforced Ef resistance against unfavorable conditions including alkaline, hypertonic, nutrient-starvation, and antibiotic challenges. Compared with monospecies and coculture species, the coaggregation of Ef and Fnp significantly facilitates both species to invade dTHP-1 cells and aid Ef to survive within the cells. Compared with coculture species, dual-species interaction of Ef and Fnp significantly decreased the levels of pro-inflammatory cytokines IL-6, TNF-α, and chemokines MCP-1 secreted by dTHP-1 cells and lessened the phosphorylation of p38, JNK, and p65 signaling pathways. The transcriptome sequencing results showed that 111 genes were differentially expressed or Ef-Fnp coaggregated species compared to Ef monospecies; 651 genes were differentially expressed for Fnp when coaggregation with Ef. The analysis of KEGG pathway showed that Ef differentially expressed genes (DEGs) were enriched in quorum sensing and arginine biosynthesis pathway; Fnp DEGs were differentially concentrated in lipopolysaccharide (LPS) biosynthesis, biofilm formation, and lysine degradation pathway compared to monospecies. KEY POINTS: • Coaggregated with Fnp aids Ef's survival in environmental stress, especially in root canals after endodontic treatment. • The coaggregation of Ef and Fnp may weaken the pro-inflammatory response and facilitate Ef to evade killed by macrophages. • The coaggregation between Ef and Fnp altered interspecies transcriptional profiles.
为了研究属间细菌种间的细胞间相互作用,本研究检测了粪肠球菌(Ef)在单种或共聚状态下在环境胁迫下与核梭杆菌亚种多形亚种(Fnp)共生时的存活情况。Ef 和 Fnp 以不同形式感染人巨噬细胞(Ef 和 Fnp 单种、Ef-Fnp 共聚、Ef+Fnp 共培养),以探索其免疫调节作用和相关分子机制。同时,还分析了共聚 Ef 和 Fnp 的转录组谱。Ef 在 90 分钟内通过形成多重聚集体与 Fnp 强烈共聚。与 Fnp 共聚增强了 Ef 对包括碱性、高渗、营养饥饿和抗生素挑战等不利条件的抗性。与单种和共培养种相比,Ef 和 Fnp 的共聚显著促进了两种细菌对 dTHP-1 细胞的侵袭,并帮助 Ef 在细胞内存活。与共培养种相比,Ef 和 Fnp 的双种相互作用显著降低了 dTHP-1 细胞分泌的促炎细胞因子 IL-6、TNF-α 和趋化因子 MCP-1 的水平,并减少了 p38、JNK 和 p65 信号通路的磷酸化。转录组测序结果表明,与 Ef 单种相比,Ef-Fnp 共聚种有 111 个基因差异表达;当与 Ef 共聚时,Fnp 有 651 个基因差异表达。KEGG 通路分析表明,Ef 差异表达基因(DEGs)富集在群体感应和精氨酸生物合成途径;与单种相比,Fnp DEGs 差异集中在脂多糖(LPS)生物合成、生物膜形成和赖氨酸降解途径。关键点:• 与 Fnp 共聚有助于 Ef 在环境压力下生存,尤其是在牙髓治疗后根管内。• Ef 和 Fnp 的共聚可能会减弱促炎反应并促进 Ef 逃避巨噬细胞的杀伤。• Ef 和 Fnp 之间的共聚改变了种间转录谱。
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