RRC ID 46861
Author Nagi M, Tanabe K, Ueno K, Nakayama H, Aoyama T, Chibana H, Yamagoe S, Umeyama T, Oura T, Ohno H, Kajiwara S, Miyazaki Y.
Title The Candida glabrata sterol scavenging mechanism, mediated by the ATP-binding cassette transporter Aus1p, is regulated by iron limitation.
Journal Mol. Microbiol.
Abstract During disseminated infection by the opportunistic pathogen Candida glabrata, uptake of sterols such as serum cholesterol may play a significant role during pathogenesis. The ATP-binding cassette transporter Aus1p is thought to function as a sterol importer and in this study, we show that uptake of exogenous sterols occurred under anaerobic conditions in wild-type cells of C. glabrata but not in AUS1-deleted mutant (aus1Δ) cells. In aerobic cultures, growth inhibition by fluconazole was prevented in the presence of serum, and AUS1 expression was upregulated. Uptake of sterol by azole treated cells required the presence of serum, and sterol alone did not reverse FLC inhibition of growth. However, if iron availability in the growth medium was limited by addition of the iron chelators ferrozine or apo-transferrin, growth of wild-type cells, but not aus1Δ cells, was rescued. In a mouse model of disseminated infection, the C. glabrata aus1Δ strain caused a significantly decreased kidney fungal burden than the wild-type strain or a strain in which AUS1 was restored. We conclude that sterol uptake in C. glabrata can occur in iron poor environment of host tissues and thus may contribute to C. glabrata pathogenesis.
Volume 88(2)
Pages 371-81
Published 2013-4
DOI 10.1111/mmi.12189
PMID 23448689
MeSH ATP-Binding Cassette Transporters / genetics ATP-Binding Cassette Transporters / metabolism* Aerobiosis Anaerobiosis Animals Candida glabrata / genetics Candida glabrata / metabolism* Candida glabrata / pathogenicity* Candidiasis / microbiology Fungal Proteins / genetics Fungal Proteins / metabolism Gene Deletion Gene Expression Regulation, Fungal* / drug effects Iron / metabolism* Kidney / microbiology Male Mice Mice, Inbred BALB C Spleen / microbiology Sterols / metabolism*
IF 3.816
Times Cited 11
Pathogenic microorganisms ?