PDF(Pubmed)
Abstract：
UNASSIGNED: This study unveils the intricate functional association between cyclic di-3\',5\'-adenylic acid (c-di-AMP) signaling, cellular bioenergetics, and the regulation of lipopolysaccharide (LPS) profile in Porphyromonas gingivalis, a Gram-negative obligate anaerobe considered as a keystone pathogen involved in the pathogenesis of chronic periodontitis. Previous research has identified variations in P. gingivalis LPS profile as a major virulence factor, yet the underlying mechanism of its modulation has remained elusive.
UNASSIGNED: We employed a comprehensive methodological approach, combining two mutants exhibiting varying levels of c-di-AMP compared to the wild type, alongside an optimized analytical methodology that combines conventional mass spectrometry techniques with a novel approach known as FLATn.
UNASSIGNED: We demonstrate that c-di-AMP acts as a metabolic nexus, connecting bioenergetic status to nuanced shifts in fatty acid and glycosyl profiles within P. gingivalis LPS. Notably, the predicted regulator gene cdaR, serving as a potent regulator of c-di-AMP synthesis, was found essential for producing N-acetylgalactosamine and an unidentified glycolipid class associated with the LPS profile.
UNASSIGNED: The multifaceted roles of c-di-AMP in bacterial physiology are underscored, emphasizing its significance in orchestrating adaptive responses to stimuli. Furthermore, our findings illuminate the significance of LPS variations and c-di-AMP signaling in determining the biological activities and immunostimulatory potential of P. gingivalis LPS, promoting a pathoadaptive strategy. The study expands the understanding of c-di-AMP pathways in Gram-negative species, laying a foundation for future investigations into the mechanisms governing variations in LPS structure at the molecular level and their implications for host-pathogen interactions.
UNASSIGNED: We employed a comprehensive methodological approach, combining two mutants exhibiting varying levels of c-di-AMP compared to the wild type, alongside an optimized analytical methodology that combines conventional mass spectrometry techniques with a novel approach known as FLATn.
UNASSIGNED: We demonstrate that c-di-AMP acts as a metabolic nexus, connecting bioenergetic status to nuanced shifts in fatty acid and glycosyl profiles within P. gingivalis LPS. Notably, the predicted regulator gene cdaR, serving as a potent regulator of c-di-AMP synthesis, was found essential for producing N-acetylgalactosamine and an unidentified glycolipid class associated with the LPS profile.
UNASSIGNED: The multifaceted roles of c-di-AMP in bacterial physiology are underscored, emphasizing its significance in orchestrating adaptive responses to stimuli. Furthermore, our findings illuminate the significance of LPS variations and c-di-AMP signaling in determining the biological activities and immunostimulatory potential of P. gingivalis LPS, promoting a pathoadaptive strategy. The study expands the understanding of c-di-AMP pathways in Gram-negative species, laying a foundation for future investigations into the mechanisms governing variations in LPS structure at the molecular level and their implications for host-pathogen interactions.
摘要：
■这项研究揭示了环状di-3'之间复杂的功能关联，5'-腺苷酸（c-di-AMP）信号，细胞生物能学，以及牙龈卟啉单胞菌中脂多糖（LPS）谱的调节，一种革兰氏阴性专性厌氧菌，被认为是参与慢性牙周炎发病机理的主要病原体。以前的研究已经确定牙龈卟啉单胞菌LPS谱的变化是主要的毒力因子，然而，其调节的潜在机制仍然难以捉摸。
■我们采用了全面的方法论方法，与野生型相比，两种突变体表现出不同水平的c-di-AMP，除了优化的分析方法，结合了传统的质谱技术和一种称为FLATn的新方法。
■我们证明了c-di-AMP作为代谢纽带，将生物能状态与牙龈卟啉单胞菌LPS内脂肪酸和糖基谱的细微变化联系起来。值得注意的是,预测的调节基因cdaR，作为c-di-AMP合成的有效调节剂，被发现对于产生N-乙酰半乳糖胺和与LPS谱相关的未知糖脂类至关重要。
■强调了c-di-AMP在细菌生理学中的多方面作用，强调其在协调对刺激的适应性反应中的重要性。此外，我们的发现阐明了LPS变化和c-di-AMP信号在确定牙龈卟啉单胞菌LPS的生物学活性和免疫刺激潜力中的意义。促进病态适应策略。该研究扩展了对革兰氏阴性物种中c-di-AMP途径的理解，为将来在分子水平上控制LPS结构变化的机制及其对宿主-病原体相互作用的影响奠定基础。
■我们采用了全面的方法论方法，与野生型相比，两种突变体表现出不同水平的c-di-AMP，除了优化的分析方法，结合了传统的质谱技术和一种称为FLATn的新方法。
■我们证明了c-di-AMP作为代谢纽带，将生物能状态与牙龈卟啉单胞菌LPS内脂肪酸和糖基谱的细微变化联系起来。值得注意的是,预测的调节基因cdaR，作为c-di-AMP合成的有效调节剂，被发现对于产生N-乙酰半乳糖胺和与LPS谱相关的未知糖脂类至关重要。
■强调了c-di-AMP在细菌生理学中的多方面作用，强调其在协调对刺激的适应性反应中的重要性。此外，我们的发现阐明了LPS变化和c-di-AMP信号在确定牙龈卟啉单胞菌LPS的生物学活性和免疫刺激潜力中的意义。促进病态适应策略。该研究扩展了对革兰氏阴性物种中c-di-AMP途径的理解，为将来在分子水平上控制LPS结构变化的机制及其对宿主-病原体相互作用的影响奠定基础。
