Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-7-30
pubmed:abstractText
We have previously demonstrated the antifungal activity of the weak bases chloroquine and quinacrine against Cryptococcus neoformans. Quinacrine, being fluorescent, was seen to be concentrated within a complex vacuolar structure within the cryptococcal cell. Here we determined the pH of this compartment using the pH-sensitive fluorescent dye, 5-(and 6-) carboxy-2',7'-dichlorofluorescein diacetate (carboxy-DCFDA). Carboxy-DCFDA was concentrated within the cryptococcal vacuole, giving a pattern of fluorescence similar to that previously observed with quinacrine. For each experiment, a standard curve of fluorescence ratio against pH was generated using buffers of defined pH containing a mixture of ionophores and inhibitors to equilibrate vacuolar pH with that of the medium. The pH of the cryptococcal vacuole of five strains was calculated to range from 5.3 to 5.9 with a mean of 5.6. This acidic pH is consistent with a model in which weak bases such as chloroquine and quinacrine are accumulated, by ion trapping within the fungal vacuole. Antifungal activity may result from the consequent disruption of pH-dependent processes as well as effects on other as yet undefined fungal targets.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1369-3786
pubmed:author
pubmed:issnType
Print
pubmed:volume
40
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
329-32
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Determination of the pH of the Cryptococcus neoformans vacuole.
pubmed:affiliation
Department of Infectious Diseases, St George's Hospital Medical School, London, UK.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't