Abstract
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 Mycobacterium tuberculosis (Mtb), the causative agent of TB. Here we report the impact of cigarette smoke condensate (CSC) on survival, mutation frequency, and gene expression of Mtb in vitro. We show that exposure of virulent Mtb 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 Mtb to respond to oxidative stress, survival, and granuloma formation in vivo. A high-SigH expression phenotype is known to be associated with greater virulence of Mtb. 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.
Highlights
Cigarette smoking is practiced by an estimated 20.7% of the world’s population, 80% of which belong to low- and middle-income countries
This was as a result of cigarette smoke condensate (CSC) and not the diluent, dimethyl sulfoxide (DMSO), since growth was observed up to 3.125% DMSO and only 0.78% DMSO was present in the 62.5-μg/ml CSC well
Survival was assessed by colony-forming unit (CFU) enumeration and relative to DMSO exposure, which was set as 100% survival
Summary
Cigarette smoking is practiced by an estimated 20.7% of the world’s population, 80% of which belong to low- and middle-income countries. Smoking is considered 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 (WHO, 2019). Many studies have indicated a link between risk of active TB and cigarette smoke, with some predicting as much as a fivefold increase in the risk of active TB in smokers compared to non-smokers (Yu et al, 1988; Jha et al, 2008; Lin et al, 2009; Rao et al, 2012, 2017; Ozturk et al, 2014; Smith et al, 2015; Bronner Murrison et al, 2016).
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