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The C andida glabrata sterol scavenging mechanism, mediated by the ATP ‐binding cassette transporter A us1p, is regulated by iron limitation
Author(s) -
Nagi Minoru,
Tanabe Koichi,
Ueno Keigo,
Nakayama Hironobu,
Aoyama Toshihiro,
Chibana Hiroji,
Yamagoe Satoshi,
Umeyama Takashi,
Oura Takahiro,
Ohno Hideaki,
Kajiwara Susumu,
Miyazaki Yoshitsugu
Publication year - 2013
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/mmi.12189
Subject(s) - biology , sterol , candida glabrata , mutant , transferrin , transporter , wild type , microbiology and biotechnology , pathogenesis , atp binding cassette transporter , biochemistry , cholesterol , gene , antifungal , immunology
Summary During disseminated infection by the opportunistic pathogen C andida glabrata , uptake of sterols such as serum cholesterol may play a significant role during pathogenesis. The ATP ‐binding cassette transporter A us1p 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 AUS 1 ‐deleted mutant ( aus1 Δ) cells. In aerobic cultures, growth inhibition by fluconazole was prevented in the presence of serum, and AUS 1 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 aus1 Δ cells, was rescued. In a mouse model of disseminated infection, the C . glabrata aus1 Δ strain caused a significantly decreased kidney fungal burden than the wild‐type strain or a strain in which AUS 1 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.