The Candida glabrata putative sterol transporter gene CgAUS1 protects cells against azoles in the presence of serum

Nakayama, Hironobu; Tanabe, Koichi; Bard, Martin; Hodgson, W. A.; Wu, Sung; Takemori, Daiki; Aoyama, Toshihiro; Kumaraswami, N. Selvamuthu; Metzler, Laurel J.; Takano, Yukie; Chibana, Hiroji; Niimi, Masakazu

doi:10.1093/jac/dkm321

Cited by 69 publications

(70 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…On the other hand, C. glabrata is capable of slow sterol import under normoxic conditions, mostly in the postexponential phases of growth. When grown in the presence of fluconazole and/or exogenous sterols in liquid medium, no increase in sterol uptake can be detected, as described previously (28). Moreover, although the sterol transporter CgAUS1 was described to be transcriptionally induced by the presence of serum in the liquid medium within a matter of hours (28), we did not observe any alteration in sterol import.…”

Section: Discussionsupporting

confidence: 71%

“…glabrata behaves as described previously (28). In normoxic conditions the parental strain is able to overcome ergosterol biosynthesis block caused by fluconazole only in the presence of serum, while the supplementation with cholesterol does not provide any advantage (Fig.…”

Section: Resultssupporting

confidence: 56%

“…For this reason, we focused on fluconazole and its possible role in sterol uptake in the three fungal species. Fetal bovine serum (FBS) and bile have also been described as substrates that may induce sterol uptake in C. glabrata (28). Thus, we analyzed these compounds and their relationship to sterol uptake in the three fungal species.…”

Section: Resultsmentioning

confidence: 99%

“…However, C. glabrata differs in the conditions of sterol import. Recent studies (27,28) revealed that C. glabrata wild-type strains import sterol under aerobic conditions, independent of the mutations in heme synthesis or the Upc2 orthologs that are required for S. cerevisiae aerobic sterol uptake. Wild-type C. glabrata responds to sterol-containing serum and bile, but not free cholesterol, whereas CgERG mutants can utilize free sterols, as well as components containing sterol.…”

mentioning

confidence: 99%

“…CgAus1 is transcriptionally induced in the presence of serum, a process dependent on the C. glabrata paralogs CgUPC2A and CgUPC2B (28).…”

mentioning

confidence: 99%

See 4 more Smart Citations

Comparison of Sterol Import under Aerobic and Anaerobic Conditions in Three Fungal Species, Candida albicans, Candida glabrata, and Saccharomyces cerevisiae

2013

View full text Add to dashboard Cite

bSterol import has been characterized under various conditions in three distinct fungal species, the model organism Saccharomyces cerevisiae and two human fungal pathogens Candida glabrata and Candida albicans, employing cholesterol, the sterol of higher eukaryotes, as well as its fungal equivalent, ergosterol. Import was confirmed by the detection of esterified cholesterol within the cells. Comparing the three fungal species, we observe sterol import under three different conditions. First, as previously well characterized, we observe sterol import under low oxygen levels in S. cerevisiae and C. glabrata, which is dependent on the transcription factor Upc2 and/or its orthologs or paralogs. Second, we observe sterol import under aerobic conditions exclusively in the two pathogenic fungi C. glabrata and C. albicans. Uptake emerges during post-exponential-growth phases, is independent of the characterized Upc2-pathway and is slower compared to the anaerobic uptake in S. cerevisiae and C. glabrata. Third, we observe under normoxic conditions in C. glabrata that Upc2-dependent sterol import can be induced in the presence of fetal bovine serum together with fluconazole. In summary, C. glabrata imports sterols both in aerobic and anaerobic conditions, and the limited aerobic uptake can be further stimulated by the presence of serum together with fluconazole. S. cerevisiae imports sterols only in anaerobic conditions, demonstrating aerobic sterol exclusion. Finally, C. albicans imports sterols exclusively aerobically in post-exponential-growth phases, independent of Upc2. For the first time, we provide direct evidence of sterol import into the human fungal pathogen C. albicans, which until now was believed to be incapable of active sterol import.

show abstract

Section: Discussionsupporting

confidence: 71%

Section: Resultssupporting

confidence: 56%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

“…CgAus1 is transcriptionally induced in the presence of serum, a process dependent on the C. glabrata paralogs CgUPC2A and CgUPC2B (28).…”

mentioning

confidence: 99%

See 3 more Smart Citations

Comparison of Sterol Import under Aerobic and Anaerobic Conditions in Three Fungal Species, Candida albicans, Candida glabrata, and Saccharomyces cerevisiae

2013

View full text Add to dashboard Cite

show abstract

Protein‐facilitated transport of hydrophobic molecules across the yeast plasma membrane

2019

View full text Add to dashboard Cite

In yeasts, the plasma membrane forms the barrier that protects the cell from the outside world, but also gathers and keeps valuable compounds inside. Although it is often suggested that hydrophobic molecules surpass this checkpoint by simple diffusion, it now becomes evident that protein‐facilitated transport mechanisms allow for selective import and export of triglycerides, fatty acids, alkanes, and sterols in yeasts. During biomass production, hydrophobic carbon sources enter and exit the cell efficiently in a strictly regulated manner that helps avoid toxicity. Furthermore, various molecules, such as yeast pheromones, secondary metabolites and xenobiotics, are exported to ensure cell–cell communication, or increase chances of survival. This review summarizes the current knowledge on how hydrophobic compounds interact with protein‐facilitated transport systems on the plasma membrane and how selective import and export across the yeast plasma membrane is achieved. Both the model organism Saccharomyces cerevisiae, as well as unconventional yeasts are discussed.

show abstract

Transcription factors and ABC transporters: from pleiotropic drug resistance to cellular signaling in yeast

Buechel

Pinkett

2020

FEBS Letters

View full text Add to dashboard Cite

Budding yeast S. cerevisiae survives in microenvironments utilizing networks of regulators and ATPbinding cassette (ABC) transporters to circumvent toxins and a variety of drugs. Our understanding of transcriptional regulation of ABC transporters in yeast is mainly derived from the study of multidrug resistance protein networks. Over the past two decades, this research has not only expanded the role of transcriptional regulators in pleiotropic drug resistance (PDR) but evolved to include the role that regulators play in cellular signaling and environmental adaptation. Inspection of the gene networks of the transcriptional regulators and characterization of the ABC transporters has clarified that they also contribute to environmental adaptation by controlling plasma-membrane composition, toxic-metal sequestration, and oxidative-stress adaptation. Additionally, ABC transporters and their regulators appear to be involved in cellular signaling for adaptation of S. cerevisiae populations to nutrient availability. In this review we summarize the current understanding of the S. cerevisiae transcriptional regulatory networks and highlight recent work in other notable fungal organisms, underlining the expansion of the study of these gene networks across the kingdom fungi.

show abstract

The Candida glabrata putative sterol transporter gene CgAUS1 protects cells against azoles in the presence of serum

Abstract: CgAUS1 appears to function as a sterol transporter that may contribute to lower azole susceptibility in the presence of serum and to protect C. glabrata against azole toxicity in vivo.

Cited by 69 publications

References 27 publications

Comparison of Sterol Import under Aerobic and Anaerobic Conditions in Three Fungal Species, Candida albicans, Candida glabrata, and Saccharomyces cerevisiae

Comparison of Sterol Import under Aerobic and Anaerobic Conditions in Three Fungal Species, Candida albicans, Candida glabrata, and Saccharomyces cerevisiae

Protein‐facilitated transport of hydrophobic molecules across the yeast plasma membrane

Transcription factors and ABC transporters: from pleiotropic drug resistance to cellular signaling in yeast

Contact Info

Product

Resources

About