Nicotinamide-An Immune-Boosting Agent to Combat Antibiotic-Resistant Pathogens

描述（由申请方提供）：烟酰胺或维生素B3通常用作治疗多种人类疾病的免疫调节剂。我们最近已经表明，烟酰胺对金黄色葡萄球菌具有有效的抗微生物活性，并通过激活转录调节因子CEBP β及其下游抗微生物效应物来刺激宿主杀死病原体。烟酰胺在S之前或之后给药有效。金黄色葡萄球菌感染，并且在初步实验中，烟酰胺还显示出针对革兰氏阴性病原体如克雷伯氏菌和假单胞菌的选择的显著活性。基于这些发现，我们建议研究烟酰胺作为免疫增强剂对更广泛病原体的有效性，包括具有显著耐药性特征的革兰氏阳性和革兰氏阴性细菌。我们将研究和优化烟酰胺治疗策略，为未来临床试验的设计提供信息。

DESCRIPTION (provided by applicant): Nicotinamide or vitamin B3 is commonly used as an immunomodulatory agent in treatment of a number of human diseases. We have recently shown that nicotinamide has potent antimicrobial activity against Staphylococcus aureus and stimulates host killing of the pathogen through activation of transcription regulator CEBP epsilon and its downstream antimicrobial effectors. Nicotinamide is effective when administered prior or after S. aureus infection, and in preliminary experiments, nicotinamide also shows significant activity against select against Gram-negative pathogens such as Klebsiella and Pseudomonas. Based on these findings, we propose to investigate the efficacy of nicotinamide as an immune boosting agent against a broader range of pathogens, including Gram-positive and Gram-negative bacteria with significant antibiotic-resistance profile. We will investigate and optimize nicotinamide treatment strategies to inform on the designs of future clinical trials.