Willemse Danicke, Moodley Chivonne, Mehra Smriti, Kaushal Deepak
Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, United States.
Tulane National Primate Research Center, Tulane University Health Sciences Center, Covington, LA, United States.
Front Microbiol. 2021 Oct 15;12:744800. doi: 10.3389/fmicb.2021.744800. eCollection 2021.
Smoking is known to be an added risk factor for tuberculosis (TB), with nearly a quarter of the TB cases attributed to cigarette smokers in the 22 countries with the highest TB burden. Many studies have indicated a link between risk of active TB and cigarette smoke. Smoking is also known to significantly decrease TB cure and treatment completion rate and increase mortality rates. Cigarette smoke contains thousands of volatile compounds including carcinogens, toxins, reactive solids, and oxidants in both particulate and gaseous phase. Yet, to date, limited studies have analyzed the impact of cigarette smoke components on (), the causative agent of TB. Here we report the impact of cigarette smoke condensate (CSC) on survival, mutation frequency, and gene expression of . We show that exposure of virulent to cigarette smoke increases the mutation frequency of the pathogen and strongly induces the expression of the regulon controlled by SigH-a global transcriptional regulator of oxidative stress. SigH has previously been shown to be required for to respond to oxidative stress, survival, and granuloma formation . A high-SigH expression phenotype is known to be associated with greater virulence of . In patients with pulmonary TB who smoke, these changes may therefore play an important, yet unexplored, role in the treatment efficacy by potentially enhancing the virulence of tubercle bacilli.
众所周知，吸烟是结核病的一个额外风险因素，在结核病负担最高的22个国家中，近四分之一的结核病病例归因于吸烟者。许多研究表明活动性结核病风险与香烟烟雾之间存在联系。吸烟还会显著降低结核病的治愈率和治疗完成率，并增加死亡率。香烟烟雾包含数千种挥发性化合物，包括颗粒相和气态相中的致癌物、毒素、反应性固体和氧化剂。然而，迄今为止，仅有有限的研究分析了香烟烟雾成分对结核病病原体（）的影响。在此，我们报告了香烟烟雾冷凝物（CSC）对（）的生存、突变频率和基因表达的影响。我们发现，将强毒力的（）暴露于香烟烟雾中会增加病原体的突变频率，并强烈诱导由SigH（一种氧化应激的全局转录调节因子）控制的调节子的表达。此前已表明，SigH是（）应对氧化应激、生存和肉芽肿形成所必需的。已知高SigH表达表型与（）更强的毒力相关。因此，在吸烟的肺结核患者中，这些变化可能通过潜在增强结核杆菌的毒力，在治疗效果中发挥重要但尚未被探索的作用。
