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Pleiotropic effects of the vacuolar ABC transporter MLT1 of Candida albicans on cell function and virulence

Nitesh Kumar Khandelwal1, Philipp Kaemmer2, Toni M Förster2

  • 1School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.

The Biochemical Journal
|March 31, 2016
PubMed

Insights

The ATP-binding cassette (ABC) transporter Mlt1p in Candida albicans impacts lipid homeostasis, affecting endocytosis, virulence, and fungal development. This study reveals new roles for ABC transporters beyond drug resistance.

Area of Science:

  • Molecular biology
  • Biochemistry
  • Mycology

Background:

  • Multidrug resistance (MDR) in Candida albicans is often linked to ATP-binding cassette (ABC) transporters like Cdr1p and Cdr2p.
  • The genome of C. albicans contains numerous ABC transporter genes, suggesting diverse physiological functions beyond MDR.

Purpose of the Study:

  • To investigate the physiological roles of the ABC transporter Mlt1p in Candida albicans.
  • To understand the impact of Mlt1p on cellular processes including lipid homeostasis, endocytosis, and virulence.

Main Methods:

  • Transcriptional profiling of a mlt1 deletion mutant (mlt1∆/∆).
  • High-throughput mass spectrometry (MS)-based lipidome analysis.
  • Assessment of endocytosis, reactive oxygen species (ROS) sequestration, hyphal development, and virulence in the mutant.

Main Results:

  • Mlt1p is localized to the vacuolar membrane and transports phosphatidylcholine (PC).
  • mlt1∆/∆ mutants exhibit down-regulation of genes involved in endocytosis, oxidoreductase activity, virulence, and hyphal development.
  • Mlt1p deficiency disrupts lipid homeostasis, leading to delayed endocytosis, impaired ROS sequestration, defective hyphal growth, and reduced virulence.

Conclusions:

  • Mlt1p plays a critical role in maintaining lipid homeostasis and regulating key cellular processes in C. albicans.
  • This study highlights unconventional functions of ABC transporters, extending their known roles beyond multidrug resistance.
Keywords:
ABC transporterCandida albicansMLT1phosphotidylcholinevirulence

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