NMR-resolved dynamics of C. difficile metabolism

摘要：艰难梭状芽胞杆菌是引起医院感染的最常见的原因。 (HAIS)。作为一种必需的厌氧病原体，艰难梭菌可以消耗多种碳源来 支持肠道定植和感染。尤其是糖酵解和粘性氨基酸 发酵途径已被证明支持快速生长，这一发现也发生在 抗生素治疗通过消除竞争对手而提高这些营养源的可用性 共生物种。然而，专性厌氧菌的代谢途径仍然 识别针对C.的预防和治疗干预措施的能力不明确、有限。 艰难梭菌的核心生理学。为了解决这些限制，我们将使用碳-13(13C)核磁共振 艰难梭菌的动态代谢，以提供基因组规模的代谢模型，并清楚地定义 产能糖酵解和氨基酸发酵的代谢融合点 小路。研究结果将在目标基因突变株中进行评估，并结合 可发酵碳源，以评估其对病原体生长和毒力的影响。

Abstract: Clostridioides difficile is the most prevalent cause of hospital associated infections (HAIs). As an obligately anaerobic pathogen, C. difficile can consume diverse carbon sources to support gut colonization and infection. In particular, glycolytic and Stickland amino acid fermentation pathways have been shown to support rapid growth, a finding that also occurs after antibiotic treatment elevates availability of these nutrient sources by removing competitive commensal species. However, the metabolic pathways of obligately anaerobic bacteria remain ill-defined, limiting capacity to identify preventive and therapeutic interventions that target C. difficile’s core physiology. To address these limitations, we will employ carbon-13 (13C) NMR of C. difficile’s dynamic metabolism to inform a genome-scale metabolic model and clearly define metabolic integration points among energy-generating glycolytic and amino acid fermentation pathways. Findings will be evaluated in targeted genetic mutants and with combinations of fermentable carbon sources to evaluate their impact on pathogen growth and virulence.