Cigarette smoke modulates virulence-related properties and host immune responses in Klebsiella pneumoniae

作者：Eltwisy HO, Abdel-Fattah M, Elsayed KNM, Assiri RA, Seif Eldin S, Elkhawaga AA, Khalifa MM, Ahmed M · 发表于：Frontiers in cellular and infection microbiology · 年份：2026 · DOI：10.3389/fcimb.2026.1787424 · 被引用次数：58 · 研究领域：Klebsiella pneumoniae、Host-Pathogen Interactions、Smoke、Humans、Virulence、Macrophages、Phagocytosis、Biofilms、Klebsiella Infections、Virulence Factors、Cytokines、Neutrophils

INTRODUCTION: Cigarette smoke is a major risk factor for respiratory infections and chronic inflammatory lung diseases, yet the mechanisms through which it alters host-pathogen interactions remain incompletely understood. Klebsiella pneumoniae is an opportunistic Gram-negative pathogen that causes severe infections, particularly in susceptible individuals. This study investigated the effects of cigarette smoke extract (CSE) on K. pneumoniae virulence-associated traits and host immune responses. METHODS: Three multidrug-resistant, extended-spectrum β-lactamase-producing clinical K. pneumoniae isolates were exposed to CSE. Bacterial growth, virulence gene expression (mrkA, luxS, and AcrB), biofilm formation, antimicrobial susceptibility, macrophage invasion, neutrophil phagocytosis, and cytokine responses in THP-1-derived macrophages were evaluated using microbiological, molecular, and cell culture assays. RESULTS: High concentrations of CSE (≥25%) suppressed bacterial growth, whereas 5-10% CSE had minimal effects. Exposure to 10% CSE significantly upregulated mrkA, luxS, and AcrB expression. Biofilm formation increased by 20.8-37.0%, and minimum inhibitory concentrations of ciprofloxacin and tigecycline increased two-fold following CSE exposure. CSE enhanced bacterial invasion of THP-1 macrophages and impaired neutrophil phagocytosis, reducing bacterial uptake by 17.8% and 29.9% after 30 and 60 min, respectively. Furthermore, CSE promoted a pro-inflammatory response characte...