Abstract

Nicotinamide adenine dinucleotide (NAD⁺) is a major cofactor in redox reactions in all lifeforms. A stable level of NAD⁺ is vital to ensure cellular homeostasis. Some pathogens can modulate NAD⁺ metabolism to their advantage and even utilize or cleave NAD⁺ from the host using specialized effectors known as ADP-ribosyltransferase toxins and NADases, leading to energy store depletion, immune evasion, or even cell death. This review explores recent advances in the field of bacterial NAD⁺-targeting toxins, highlighting the relevance of NAD⁺ modulation as an emerging pathogenesis strategy. In addition, we discuss the role of specific NAD⁺-targeting toxins in niche colonization and bacterial lifestyle as components of Toxin/Antitoxin systems and key players in inter-bacterial competition. Understanding the mechanisms of toxicity, regulation, and secretion of these toxins will provide interesting leads in the search for new antimicrobial treatments in the fight against infectious diseases.

中文翻译：

---

细菌靶向NAD+：发病机制中的新兴武器

摘要

烟酰胺腺嘌呤二核苷酸 (NAD ⁺ ) 是所有生命形式中氧化还原反应的主要辅助因子。稳定的 NAD ⁺水平对于确保细胞稳态至关重要。一些病原体可以调节 NAD ⁺代谢以发挥其优势，甚至使用称为 ADP-核糖基转移酶毒素和 NADase 的特殊效应器从宿主中利用或切割 NAD ⁺，导致能量储存耗尽、免疫逃避，甚至细胞死亡。^{本综述探讨了细菌 NAD +}靶向毒素领域的最新进展，强调了 NAD ⁺调节作为新兴发病机制策略的相关性。另外，我们讨论特定NAD ^+的作用- 在生态位定植和细菌生活方式中靶向毒素，作为毒素/抗毒素系统的组成部分和细菌间竞争的关键参与者。了解这些毒素的毒性、调节和分泌机制将为寻找抗击传染病的新抗菌疗法提供有趣的线索。