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Lipidomics Approaches: Applied to the Study of Pathogenesis in Candida Species

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Yeasts in Biotechnology and Human Health

Part of the book series: Progress in Molecular and Subcellular Biology ((PMSB,volume 58))

Abstract

High rate of reported cases of infections in humans caused by fungal pathogens pose serious concern. Potentially these commensal fungi remain harmless to the healthy individuals but can cause severe systemic infection in patients with compromised immune system. Effective drug remedies against these infections are rather limited. Moreover, frequently encountered multidrug resistance poses an additional challenge to search for alternate and novel targets. Notably, imbalances in lipid homeostasis which impact drug susceptibility of Candida albicans cells do provide clues of novel therapeutic strategies. Sphingolipids (SPHs) are unique components of Candida cells, hence are actively exploited as potential drug targets. In addition, recent research has uncovered that several SPH intermediates and of other lipids as well, govern cell signaling and virulence of C. albicans. In this chapter, we highlight the role of lipids in the physiology of Candida, particularly focusing on their roles in the development of drug resistance. Considering the importance of lipids, the article also highlights recent high-throughput analytical tools and methodologies, which are being employed in our understanding of structures, biosynthesis, and roles of lipids in fungal pathogens.

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Abbreviations

MDR:

Multidrug resistance

CW:

Cell wall

CRS-MIS:

Caspofungin reduced susceptibility—micafungin increased susceptibility

LCB:

Long-chain sphingoid bases

PM:

Plasma membrane

ABC:

ATP binding cassette

MFS:

Major facilitator superfamily

PC:

Phospahtidylcholine

FD:

Facilitated diffusion

QDR:

Quinidine drug resistance

PHS:

Phytosphingosine

PG:

Phosphatidylglycerol

PS:

Phosphatidylserine

PSD:

Phosphatidylserine decarboxylase

PE:

Phosphatidylethanolamine

BMDM:

Bone marrow-derived macrophage

PI:

Phosphatidylinositol

MS/MS:

Triple quadrupole mass spectrometry

MSn:

Tandem quadrupole-linear ion trap mass spectrometry

TOF:

Time-of-flight mass spectrometry

ESI:

Electrospray ionization

MALDI:

Matrix-assisted laser desorption ionization

SPE:

Solid phase extraction

HPLC:

High-performance liquid chromatography

m/z :

Mass-to-charge ratio

MPIS:

Multiple precursor ion scanning

Pre:

Precursor

NL:

Neutral loss

PGL:

Phosphoglyceride

SPH:

Sphingolipids

PA:

Phosphatidic acid

IPC:

Inositolphosphorylceramide

MRM:

Multiple reaction monitoring

SRM:

Single reaction monitoring

LC-ESI/MSMS:

Liquid chromatography electrospray ionization tandem mass spectrometry

MIPC:

Mannosylinositolphosphoryceramide

M(IP)2C:

Mannosyldiinositolphosphoryceramide

GCMS:

Gas chromatography mass spectrometry

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Acknowledgements

We thank grants to RP from DBT No. BT/01/CEIB/10/III/02, BT/PR7392/MED/29/652/2012 and BT/PR14117/BRB/10/1420/2015. This manuscript was proofread by Madri Kakoti, Department of Linguistics, University of Lucknow, Lucknow (email: madrikakoti@gmail.com). We thank financial assistance to AS from University of Lucknow, Lucknow. AS would like to thank Amity University, Haryana for inviting for a mini sabbatical and support therein.

Financial and competing interest disclosure: There is no financial and competing interest.

Contribution to the manuscript: RP, AS and NKK wrote the manuscript.

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  1. Nitesh Kumar Khandelwal

    Present address: Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ, 85721, USA

Authors and Affiliations

  1. Department of Biochemistry, University of Lucknow, Lucknow, 226007, Uttar Pradesh, India

    Ashutosh Singh

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

    Nitesh Kumar Khandelwal

  3. Amity Institute of Integrative Sciences and Health, Amity University Haryana, Gurgaon, Haryana, India

    Rajendra Prasad

  4. Amity Institute of Biotechnology, Amity University Haryana, Gurgaon, Haryana, India

    Rajendra Prasad

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  1. Institute for Bioengineering and Biosciences (iBB) and Department of Bioengineering, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Portugal

    Isabel Sá-Correia

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Singh, A., Khandelwal, N.K., Prasad, R. (2019). Lipidomics Approaches: Applied to the Study of Pathogenesis in Candida Species. In: Sá-Correia, I. (eds) Yeasts in Biotechnology and Human Health. Progress in Molecular and Subcellular Biology, vol 58. Springer, Cham. https://doi.org/10.1007/978-3-030-13035-0_8

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