Klebsiella pneumoniae Is Able to Trigger Epithelial-Mesenchymal Transition Process in Cultured Airway Epithelial Cells

• Published in: PloS one 2016-01, Vol.11 (1), p.e0146365-e0146365
• Main Authors: Leone, Laura, Mazzetta, Francesca, Martinelli, Daniela, Valente, Sabatino, Alimandi, Maurizio, Raffa, Salvatore, Santino, Iolanda
• Format: Article
• Language: English
• Subjects: Antioxidants; Bacteria; Biology and Life Sciences; Cell Line, Tumor; Cell Survival; Epithelial cells; Epithelial Cells - cytology; Epithelial Cells - metabolism; Epithelial Cells - microbiology; Epithelial-Mesenchymal Transition; Gene expression; Genetic aspects; Genotype & phenotype; Growth factors; Homeodomain Proteins - genetics; Homeodomain Proteins - metabolism; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit - genetics; Hypoxia-Inducible Factor 1, alpha Subunit - metabolism; Infections; Inflammation; Inflammatory response; Intracellular; Klebsiella; Klebsiella pneumoniae; Klebsiella pneumoniae - isolation & purification; Klebsiella pneumoniae - physiology; Medicine; Medicine and Health Sciences; Mesenchyme; Microscopy, Fluorescence; Nosocomial infections; Oxidative stress; Oxygen; Pathogens; Phenotype; Physiological aspects; Reactive oxygen species; Reactive Oxygen Species - metabolism; Real-Time Polymerase Chain Reaction; Research and Analysis Methods; Respiratory tract; Resveratrol; Snail Family Transcription Factors; Transcription activation; Transcription factors; Transcription Factors - genetics; Transcription Factors - metabolism; Twist-Related Protein 1 - genetics; Twist-Related Protein 1 - metabolism; Up-Regulation; Zinc Finger E-box-Binding Homeobox 1
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0146365

The ability of some bacterial pathogens to activate Epithelial-Mesenchymal Transition normally is a consequence of the persistence of a local chronic inflammatory response or depends on a direct interaction of the pathogens with the host epithelial cells. In this study we monitored the abilities of the K. pneumoniae to activate the expression of genes related to EMT-like processes and the occurrence of phenotypic changes in airway epithelial cells during the early steps of cell infection. We describe changes in the production of intracellular reactive oxygen species and increased HIF-1α mRNA expression in cells exposed to K. pneumoniae infection. We also describe the upregulation of a set of transcription factors implicated in the EMT processes, such as Twist, Snail and ZEB, indicating that the morphological changes of epithelial cells already appreciable after few hours from the K. pneumoniae infection are tightly regulated by the activation of transcriptional pathways, driving epithelial cells to EMT. These effects appear to be effectively counteracted by resveratrol, an antioxidant that is able to exert a sustained scavenging of the intracellular ROS. This is the first report indicating that strains of K. pneumoniae may promote EMT-like programs through direct interaction with epithelial cells without the involvement of inflammatory cells.