Linked Life Data

17581121

Source:http://linkedlifedata.com/resource/pubmed/id/17581121

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-6-21
pubmed:abstractText
Knockout mutants of Plasmodium falciparum lacking pfpm1, pfpm2 and pfhap (triple-PM KO), and mutants lacking all four digestive vacuole (DV) plasmepsins (pfpm4, pfpm1, pfpm2 and pfhap; quadruple-PM KO), were prepared by double cross-over integration effecting chromosomal deletions of up to 14.6 kb. The triple-PM KO was similar to the parental line (3D7) in growth rate, morphology and sensitivity to proteinase inhibitors. The quadruple-PM KO showed a significantly slower rate of growth in standard medium, which manifested as delayed schizont maturation accompanied by reduced formation of haemozoin. In amino acid-limited medium, the reduction in growth rate of the quadruple-PM KO was pronounced. The sensitivity of both the triple- and quadruple-PM KOs to six different HIV aspartic proteinase inhibitors was comparable to that of 3D7, thus establishing that the DV plasmepsins were not the primary targets of the antimalarial activity of these clinically important compounds. Electron microscopic analysis revealed the presence of multilamellar bodies resembling ceroid in the DV of the quadruple-PM KO, and intermediates of the autophagic pathway accumulated as determined by Western blot analysis. Thus, the DV plasmepsins, although not essential, contribute significantly to the fitness of the parasite and are required for efficient degradation of endosomal vesicles delivered to the DV.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0950-382X
pubmed:author
pubmed:issnType
Print
pubmed:volume
65
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
64-75
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Critical roles for the digestive vacuole plasmepsins of Plasmodium falciparum in vacuolar function.
pubmed:affiliation
Department of Infectious Diseases and Pathology, University of Florida, Gainesville, FL 32611, USA.
pubmed:publicationType
Journal Article