Abstract
Since bacterial invasion into host cells is an important step in the infection process, using the agents to interfere with bacterial internalization is an attractive approach to block the infection process. In this work, we describe a new, previously unrecognized role of the human cationic host defense peptide HMGN2 during Klebsiella pneumoniae infections. Our results revealed that the internalization of K. pneumoniae strain 03183 into cultured bladder epithelial cells (T24) was significantly reduced at HMGN2 concentrations that were unable to produce any bacteriostatic or bactericidal effect. Using microarrays and follow-up studies, we demonstrated that HMGN2 affected the internalization of K. pneumoniae strain 03183 by inhibiting the attachment of bacteria, and then decreasing bacteria-induced ERK1/2 activation and actin polymerization, which might contribute to bacterial internalization into T24 cells. This disruption of bacterial internalization implied that HMGN2 could provide protection against K. pneumoniae infections.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / metabolism
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Anti-Bacterial Agents / pharmacology
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Bacterial Adhesion / drug effects
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Blotting, Western
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Butadienes / pharmacology
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Cell Line, Tumor
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Endocytosis / drug effects*
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Enzyme Activation / drug effects
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Epithelial Cells / metabolism
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Epithelial Cells / microbiology*
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Epithelial Cells / pathology
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Flavonoids / pharmacology
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Gene Expression Profiling
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Gene Expression Regulation, Bacterial
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HMGN2 Protein / genetics
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HMGN2 Protein / pharmacology*
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Host-Pathogen Interactions / drug effects
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Humans
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Klebsiella pneumoniae / genetics
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Klebsiella pneumoniae / physiology*
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Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
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Mitogen-Activated Protein Kinase 3 / metabolism
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Nitriles / pharmacology
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Oligonucleotide Array Sequence Analysis
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Recombinant Proteins / pharmacology
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Time Factors
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Urinary Bladder Neoplasms / metabolism
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Urinary Bladder Neoplasms / microbiology
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Urinary Bladder Neoplasms / pathology
Substances
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Actins
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Anti-Bacterial Agents
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Butadienes
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Flavonoids
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HMGN2 Protein
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Nitriles
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Recombinant Proteins
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U 0126
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MAPK1 protein, human
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one