Abstract
Pseudomonas aeruginosa clinical cystic fibrosis isolate CHA was mutagenized with Tn5Tc to identify new genes involved in type III secretion system (TTSS)-dependent cytotoxicity toward human polymorphonuclear neutrophils. Among 25 mutants affected in TTSS function, 14 contained the insertion at different positions in the aceAB operon encoding the PDH-E1 and -E2 subunits of pyruvate dehydrogenase. In PDH mutants, no transcriptional activation of TTSS genes in response to calcium depletion occurred. Expression in trans of ExsA restored TTSS function and cytotoxicity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Bacterial Proteins / metabolism
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Cystic Fibrosis / microbiology
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / physiology
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Dihydrolipoyllysine-Residue Acetyltransferase
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Disease Models, Animal
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Histidine Kinase
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Humans
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L-Lactate Dehydrogenase / metabolism
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Mutagenesis, Insertional
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Neutrophils / microbiology
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Operon / physiology*
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Phosphoprotein Phosphatases / genetics
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Phosphoprotein Phosphatases / metabolism
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Pneumonia, Bacterial / microbiology
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Pore Forming Cytotoxic Proteins
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Protein Kinases / metabolism
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Pseudomonas Infections / microbiology
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Pseudomonas aeruginosa / enzymology*
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Pseudomonas aeruginosa / genetics
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Pseudomonas aeruginosa / isolation & purification
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Pseudomonas aeruginosa / pathogenicity
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Pyruvate Dehydrogenase Complex / genetics
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Pyruvate Dehydrogenase Complex / physiology*
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Rats
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Rats, Sprague-Dawley
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Trans-Activators / genetics
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Trans-Activators / physiology
Substances
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Bacterial Proteins
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DNA-Binding Proteins
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ExsA protein, bacteria
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PopB protein, Ralstonia solanacearum
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Pore Forming Cytotoxic Proteins
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Pyruvate Dehydrogenase Complex
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Trans-Activators
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pyruvate dehydrogenase multienzyme complex E1
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L-Lactate Dehydrogenase
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Dihydrolipoyllysine-Residue Acetyltransferase
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Protein Kinases
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Histidine Kinase
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Phosphoprotein Phosphatases
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protein phosphatase 4