title: Klebsiella pneumoniae Is Able to Trigger Epithelial-Mesenchymal Transition Process in Cultured Airway Epithelial Cells.
abstract: 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.
authors.affiliation: Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Leone
authors.affiliation: Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Mazzetta
authors.affiliation: Microbiology Unit, Azienda Ospedaliera Sant'Andrea, Rome, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Martinelli
authors.affiliation: Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Sabatino
authors.initials: S
authors.lastname: Valente
authors.affiliation: Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: Alimandi
authors.affiliation: Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.|Cellular Diagnostics Unit, Azienda Ospedaliera Sant'Andrea, Rome, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Raffa
authors.affiliation: Department of Clinical and Molecular Medicine, Sapienza University of Rome, Rome, Italy.|Microbiology Unit, Azienda Ospedaliera Sant'Andrea, Rome, Italy.
authors.forename: Iolanda
authors.initials: I
authors.lastname: Santino
mesh_terms: D045744:Cell Line, Tumor; D002470:Cell Survival; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D058750:Epithelial-Mesenchymal Transition; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007711:Klebsiella pneumoniae / Q000302:isolation & purification / Q000502:physiology*; D008856:Microscopy, Fluorescence; D010641:Phenotype; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D000071799:Zinc Finger E-box-Binding Homeobox 1
chemical_list: D018398:Homeodomain Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017382:Reactive Oxygen Species; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051879:Twist-Related Protein 1; C486307:ZEB1 protein, human; D000071799:Zinc Finger E-box-Binding Homeobox 1
references.citation: Lancet Infect Dis. 2009 Apr;9(4):228-36
references.pmid: 19324295
references.citation: Antioxid Redox Signal. 2008 May;10(5):983-95
references.pmid: 18199003
references.citation: J Clin Invest. 2009 Jun;119(6):1420-8
references.pmid: 19487818
references.citation: BMC Microbiol. 2009;9:156
references.pmid: 19650888
references.citation: Cell Microbiol. 2010 May 1;12(5):640-53
references.pmid: 20039880
references.citation: Gut. 2010 Aug;59(8):1037-45
references.pmid: 20584780
references.citation: J Exp Med. 2010 Sep 27;207(10):2157-74
references.pmid: 20855497
references.citation: Int J Med Microbiol. 2011 Feb;301(2):97-104
references.pmid: 20940105
references.citation: J Surg Res. 2011 Apr;166(2):255-64
references.pmid: 20452613
references.citation: Eur Respir J. 2011 May;37(5):1237-47
references.pmid: 20847079
references.citation: Antimicrob Agents Chemother. 2012 Apr;56(4):2143-5
references.pmid: 22252815
references.citation: Otol Neurotol. 2012 Aug;33(6):988-95
references.pmid: 22772001
references.citation: Gut Microbes. 2012 May-Jun;3(3):176-85
references.pmid: 22572828
references.citation: PLoS One. 2013;8(2):e57659
references.pmid: 23451255
references.citation: PLoS One. 2013;8(4):e63147
references.pmid: 23646188
references.citation: Future Microbiol. 2013 Sep;8(9):1147-61
references.pmid: 24020742
references.citation: Int J Immunopathol Pharmacol. 2013 Jul-Sep;26(3):785-90
references.pmid: 24067478
references.citation: Nat Rev Mol Cell Biol. 2014 Mar;15(3):178-96
references.pmid: 24556840
references.citation: Oncogene. 2014 May 15;33(20):2639-54
references.pmid: 23752178
references.citation: Emerg Infect Dis. 2014 Jul;20(7):1170-5
references.pmid: 24959688
references.citation: J Dermatol Sci. 2009 May;54(2):106-13
references.pmid: 19250802
references.citation: Antimicrob Agents Chemother. 2015 Jan;59(1):536-43
references.pmid: 25385117
references.citation: PLoS Pathog. 2015 Jan;11(1):e1004627
references.pmid: 25633080
references.citation: Future Microbiol. 2015;10(5):743-61
references.pmid: 26000649
references.citation: Am J Physiol Lung Cell Mol Physiol. 2012 Dec 15;303(12):L1057-69
references.pmid: 23064951
references.citation: Free Radic Biol Med. 1999 Nov;27(9-10):1122-32
references.pmid: 10569645
references.citation: Biochem Pharmacol. 2000 Apr 1;59(7):865-70
references.pmid: 10718345
references.citation: J Biol Chem. 2000 Aug 18;275(33):25130-8
references.pmid: 10833514
references.citation: Biochem Biophys Res Commun. 2003 Oct 3;309(4):1017-26
references.pmid: 13679076
references.citation: Microbes Infect. 2004 Nov;6(13):1191-8
references.pmid: 15488738
references.citation: Am J Pathol. 2005 May;166(5):1321-32
references.pmid: 15855634
references.citation: Biochim Biophys Acta. 2005 Jul 25;1755(2):107-20
references.pmid: 15994012
references.citation: Proc Natl Acad Sci U S A. 2006 Aug 29;103(35):13180-5
references.pmid: 16924102
references.citation: Exp Cell Res. 2007 May 15;313(9):1866-76
references.pmid: 17451682
references.citation: Infect Immun. 2007 Aug;75(8):4030-9
references.pmid: 17562777
references.citation: Cancer Sci. 2007 Oct;98(10):1512-20
references.pmid: 17645776
references.citation: J Neuroinflammation. 2007;4:25
references.pmid: 17927823
references.citation: Neurosci Lett. 2008 Jan 31;431(2):155-60
references.pmid: 18164813
references.citation: Cell Cycle. 2008 Jul 15;7(14):2090-6
references.pmid: 18635960