The effects of e-cigarette vapor exposure on the transcriptome and virulence of Streptococcus pneumoniae

Abstract

14The effects of e-cigarette vapor (EV) exposure on the physiology of respiratory microflora are 15 not fully defined. We analyzed the effects of exposure to vapor from nicotine-containing and 16 nicotine-free e-liquid formulations on virulence and transcriptome of Streptococcus pneumoniae 17 strain TIGR4, a pathogen that asymptomatically colonizes human nasopharyngeal mucosa. 18 TIGR4 was pre-exposed for 2h to nicotine-containing EV extract (EVE+NIC), nicotine-free EV 19 extract (EVE-NIC), cigarette smoke extract (CSE), or nutrient-rich TS broth (control). The 20 differences in the treatment and control TIGR4 were explored using transcriptome sequencing, in 21 vitro virulence assays, and in vivo mouse model of acute pneumonia. The analysis of RNASeq 22 Importance 37With the increasing popularity of e-cigarettes amongst cigarette smoking and non-smoking 38 adults and children, and the recent reports of vaping related lung illnesses and deaths, further 39 analysis of the adverse health effects of e-cigarette vapor (EV) exposure is warranted. Since 40 pathogenic bacteria such as Streptococcus pneumoniae can colonize the human nasopharynx as 41 commensals, they may be affected by the exposure to bioactive chemicals in EV. Hence in this 42 study we examined the effects of EV exposure on the physiology of S. pneumoniae strain 43 TIGR4. In order to differentiate between the effects of nicotine and non-nicotine components, we 44 specifically compared RNASeq profiles and virulence of TIGR4 exposed to vapor from nicotine-45 containing and nicotine-free e-liquid formulations. We observed that nicotine-containing EV 46 augmented TIGR4 biofilms and altered expression of TIGR4 genes predominantly involved in 47 metabolism and stress response. However, neither nicotine-containing nor nicotine-free EV 48 affected TIGR4 virulence in a mouse model. 49 words 50 51The e-cigarette is a handheld device that electronically heats an e-liquid and generates 52 aerosolized e-cigarette vapor (EV) that is inhaled by the user. Originally, e-cigarettes were 53 marketed as a safer alternative to smoking and as an effective smoking cessation device. 54Contrary to these claims, emerging research has repeatedly demonstrated the adverse health 55 effects of EV exposure, and in the last decade the number of new e-cigarette users (vapers) and 56 cigarette smokers who also use e-cigarette (dual users) has increased at a rapid pace. Currently, 57 the exploding popularity of e-cigarette use (vaping) is threatening the success of various public 58 health campaigns to reduce cigarette smoking. Especially worrisome is the rise in vaping 59 amongst the youth and teenagers. In 2018, 4.9% of middle school and 20.8% of high school 60 students (~3.6 million total) in the USA reported vaping [1]. Commercially available e-liquids 61 typically contain three main ingredients: 1) a vehicle mixture of the humectants propylene glycol 62 and/or vegetable glycerin which determines vapor density and throat hit intensity; 2) flavoring 63 chemicals such as cinnamaldehyde,...

Electronic Vaping-Induced Methicillin-Sensitive Staphylococcus Aureus Pneumonia and Empyema

“…is data indicate that S. aureus infection in vapers might be lethal with difficulty in treatment. In another study, Streptococcus pneumoniae, ECVE, or CSE resulted in a modest biofilm formation with no hydrophobicity changes or epithelial cell adherence [9].…”

“…Flavoring agents used are cinnamaldehyde, diacetyl, 2, 3-pentanedione, acetoin, and maltol. Nicotine concentration varies from 0–36 mg/ml [ 9 ]. The aerosolized vapor contains numerous respiratory irritants and toxicants, such as volatile organic compounds, acrolein, and formaldehyde.…”

“…The chemicals in electronic cigarette vapor are cytotoxic, increase mucin production, and induce proinflammatory cytokines and proteases. This effect culminates in increased airway hyperreactivity and suppressed mucociliary clearance [ 9 ]. The result is the impairment of antimicrobial defenses and the destruction of lung tissue.…”

“…aureus infection in vapers might be lethal with difficulty in treatment. In another study, Streptococcus pneumoniae , ECVE, or CSE resulted in a modest biofilm formation with no hydrophobicity changes or epithelial cell adherence [ 9 ]. There is a significant disparity in the puff profile between vapers and conventional cigarette users.…”