Cigarette smoke extract induces the Pseudomonas aeruginosa nfxC drug-resistant phenotype

Background: There is clinical and epidemiological evidence indicating that cigarette smoke exposure can significantly increase the usage of antibiotics by smokers to treat pulmonary infections, suggesting an increased risk of bacterial drug resistance. Pseudomonas aeruginosa is commonly found in infectious diseases closely related to cigarette smoke exposure and frequently acquires drug resistance. Recently, a study has demonstrated that cigarette smoke extract may induce Pseudomonas aeruginosa antibiotic resistance but the mechanism remain unknown. Objectives: To explore the effect of cigarette smoke exposure on drug resistance in P. aeruginosa and the underlying mechanism using an in vitro model of cigarette smoke extract (CSE) exposure. Methods: P. aeruginosa strains PAO1, PA103 and ATCC27853 were used in this study. Changes in drug resistance in P. aeruginosa after CSE exposure were evaluated by antimicrobial susceptibility tests. Additionally, differentially expressed genes related to drug resistance were detected by transcriptome sequencing and qRT-PCR. Results: CSE increased both the MIC and MBC of levofloxacin and imipenem (MIC was not changed in ATCC 27853) against P. aeruginosa. However, CSE could only increase the minimum inhibitory concentration of tigecycline and minocycline against P. aeruginosa. Transcriptome sequencing and qRT-PCR indicated that MvaT and OprD levels decreased and MexEF-OprN levels increased. Conclusions: Overall, our results showed that CSE may induce antibiotic resistance in P. aeruginosa. The results of antimicrobial susceptibility tests, transcriptome sequencing and qRT-PCR showed that CSE induced P. aeruginosa to the nfxC drug-resistant phenotype. (C) 2020 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.