Linked Life Data

12915403

Source:http://linkedlifedata.com/resource/pubmed/id/12915403

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
42
pubmed:dateCreated
2003-10-13
pubmed:abstractText
A number of clinical isolates of Pseudomonas aeruginosa are cytotoxic to mammalian cells due to the action of the 74-kDa protein ExoU, which is secreted into host cells by the type III secretion system and whose function is unknown. Here we report that the swift and profound cytotoxicity induced by purified ExoU or by an ExoU-expressing strain of P. aeruginosa is blocked by various inhibitors of cytosolic (cPLA2) and Ca2+ -independent (iPLA2) phospholipase A2 enzymes. In contrast, no cytoprotection is offered by inhibitors of secreted phospholipase A2 enzymes or by a number of inhibitors of signal transduction pathways. This suggests that phospholipase A2 inhibitors may represent a novel mode of treatment for acute P. aeruginosa infections. We find that 300-600 molecules of ExoU/cell are required to achieve half-maximal cell killing and that ExoU localizes to the host cell plasma membrane in punctate fashion. We also show that ExoU interacts in vitro with an inhibitor of cPLA2 and iPLA2 enzymes and contains a putative serine-aspartate catalytic dyad homologous to those found in cPLA2 and iPLA2 enzymes. Mutation of either the serine or the aspartate renders ExoU non-cytotoxic. Although no phospholipase or esterase activity is detected in vitro, significant phospholipase activity is detected in vivo, suggesting that ExoU requires one or more host cell factors for activation as a membrane-lytic and cytotoxic phospholipase.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
41326-32
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:12915403-Amino Acid Sequence, pubmed-meshheading:12915403-Animals, pubmed-meshheading:12915403-Bacterial Proteins, pubmed-meshheading:12915403-CHO Cells, pubmed-meshheading:12915403-Carboxylic Ester Hydrolases, pubmed-meshheading:12915403-Chromatography, Thin Layer, pubmed-meshheading:12915403-Cricetinae, pubmed-meshheading:12915403-Cytosol, pubmed-meshheading:12915403-Enzyme Activation, pubmed-meshheading:12915403-Enzyme Inhibitors, pubmed-meshheading:12915403-Microscopy, Fluorescence, pubmed-meshheading:12915403-Molecular Sequence Data, pubmed-meshheading:12915403-Mutation, pubmed-meshheading:12915403-Phospholipases A, pubmed-meshheading:12915403-Phospholipases A2, pubmed-meshheading:12915403-Pseudomonas aeruginosa, pubmed-meshheading:12915403-Sequence Homology, Amino Acid, pubmed-meshheading:12915403-Serine, pubmed-meshheading:12915403-Signal Transduction
pubmed:year
2003
pubmed:articleTitle
In vivo phospholipase activity of the Pseudomonas aeruginosa cytotoxin ExoU and protection of mammalian cells with phospholipase A2 inhibitors.
pubmed:affiliation
Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093-0314, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't