Cited by 22Fungal and yeast genetics researchAntifungal resistance and susceptibilityFungal Infections and Studies

The phosphoinositide 3-kinase regulates retrograde trafficking of the iron permease CgFtr1 and iron homeostasis in Candida glabrata

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Sharma, Vandana, Purushotham, Rajaram, Kaur, Rupinder·2016·Journal of Biological Chemistry

Abstract

The phosphoinositide 3-kinase (PI3K), which phosphorylates phosphatidylinositol and produces PI3P, has been implicated in protein trafficking, intracellular survival, and virulence in the pathogenic yeast Candida glabrata Here, we demonstrate PI3-kinase (CgVps34) to be essential for maintenance of cellular iron homeostasis. We examine how CgVps34 regulates the fundamental process of iron acquisition, and underscore its function in vesicular trafficking as a central determinant. RNA sequencing analysis revealed iron homeostasis genes to be differentially expressed upon CgVps34 disruption. Consistently, the Cgvps34Δ mutant displayed growth attenuation in low- and high-iron media, increased intracellular iron content, elevated mitochondrial aconitase activity, impaired biofilm formation, and extenuated mouse organ colonization potential. Furthermore, we demonstrate for the first time that C. glabrata cells respond to iron limitation by expressing the iron permease CgFtr1 primarily on the cell membrane, and to iron excess via internalization of the plasma membrane-localized CgFtr1 to the vacuole. Our data show that CgVps34 is essential for the latter process. We also report that macrophage-internalized C. glabrata cells express CgFtr1 on the cell membrane indicative of an iron-restricted macrophage internal milieu, and Cgvps34Δ cells display better survival in iron-enriched medium-cultured macrophages. Overall, our data reveal the centrality of PI3K signaling in iron metabolism and host colonization.

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Crossref · 10.1074/jbc.m116.751529

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  • The ability of C. glabrata to form biofilms is enhanced in the high-iron environment.

    “The ability of C. glabrata to form biofilms has also been found to be enhanced in the high-iron environment [57].”

    From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [57]

  • There is a close association between the capacity to form biofilms and colonize murine organs in the systemic candidiasis model.

    “Moreover, recent studies have shown a close association between the capacity to form biofilms and colonize murine organs in the systemic candidiasis model [57,58], however, the precise mechanisms underlying this relationship are unknown.”

    From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [57]

  • Retrograde trafficking of CgFtr1 from the plasma membrane to the vacuole is dependent on the sole class III phosphoinositide 3-kinase kinase CgVps34.

    “This retrograde trafficking of CgFtr1 from the plasma membrane to the vacuole is dependent on the sole class III phosphoinositide 3-kinase kinase, CgVps34 [57].”

    From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [57]

  • C. glabrata responds to iron-deplete conditions via expression of the high-affinity iron permease CgFtr1 on the plasma membrane.

    “Furthermore, C. glabrata has been reported to respond to iron-deplete condition via expression of the high-affinity iron permease CgFtr1 on the plasma membrane, and to iron-replete condition by trafficking CgFtr1 to the vacuole [57].”

    From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [57]

  • C. glabrata responds to iron-replete conditions by trafficking CgFtr1 to the vacuole.

    “Furthermore, C. glabrata has been reported to respond to iron-deplete condition via expression of the high-affinity iron permease CgFtr1 on the plasma membrane, and to iron-replete condition by trafficking CgFtr1 to the vacuole [57].”

    From Candida glabrata: A Lot More Than Meets the Eye (2019) · cites this paper as [57]

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Authors
Sharma, V., Purushotham, R., & Kaur, R.
Affiliations
  • Manipal Academy of Higher Education (IN)
  • Centre for DNA Fingerprinting and Diagnostics (IN)
Corresponding author
Kaur, Rupinder
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2016-11
Volume
291
Issue
47
Pages
24715-24734
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2531585364
Cited by
22
References
61
Citations by year
2026: 2 · 2024: 1 · 2023: 5 · 2022: 1 · 2020: 6 · 2019: 4 · 2018: 1 · 2017: 2
FWCI
1.21
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
Department of Biotechnology, Ministry of Science and Technology (BT/PR5145/MED/29/470/2012, BT/PR7388/MED/29/650/2012, BT/PR7123/BRB/10/1149/2012)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Health Sciences › Medicine › Epidemiology › Fungal Infections and Studies
Keywords
phosphatidylinositol 3-kinase, Candida glabrata, iron homeostasis, iron permease, retrograde trafficking, vesicle trafficking, iron acquisition, iron limitation, iron overload, vacuoles, biofilm formation, macrophage survival, host colonization, phosphatidylinositol 3-phosphate
MeSH terms
Animals, Candidiasis, Female, Fungal Proteins, Iron, Macrophages, Mice, Inbred BALB C, Phosphatidylinositol 3-Kinases, Membrane Transport Proteins, Candida glabrata, Mice

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