Genetically Compromising Phospholipid Metabolism Limits Candida albicans’ Virulence

  • Dorothy Wong
  • James Plumb
  • Hosamiddine Talab
  • Mouhamad Kurdi
  • Keshav Pokhrel
  • Peter OelkersEmail author
Original Paper


Perturbing ergosterol synthesis has been previously shown to reduce the virulence of Candida albicans. We tested the hypothesis that further altering cell membrane composition by limiting phospholipid synthesis or remodeling will have the same effect. To model partial inhibition, C. albicans strains independently harboring heterozygous deletion of four genes that encode for enzymes that mediate phospholipid synthesis or modification were generated. Quantitative PCR determined that heterozygous deletion routinely caused a nearly 50% reduction in the respective gene’s transcript abundance. Compensatory increased transcript abundance was only found with the deletion of LRO1, a homolog of phospholipid diacylglycerol acyltransferases. Virulence of the mutants was assayed in a Caenorhabditis elegans host model. Even modestly reduced expression of LRO1, phosphatidylserine synthase (CHO1), and lysophospholipid acyltransferase (LPT1) significantly reduced virulence by 23–38%. Reintroducing a second functional allele, respectively, to all three mutants restored virulence. Heterozygous deletion of SLC1, a homolog of 1-acylglycerol-3-phosphate O-acyltransferases, did not significantly reduce virulence. Electrospray ionization tandem mass spectrometry analysis of phospholipid composition followed by principal component analysis identified comprehensive changes in the LRO1 and CHO1 deletion heterozygotes. Strikingly (p < 0.001), univariate comparisons found that both deletion heterozygotes had 20% more phosphatidylinositol, 75% less lysophosphatidylcholine, and 35% less lysophosphatidylethanolamine compared to wild type. Heterozygous deletion of LPT1 also significantly increased phosphatidylinositol abundance. No growth phenotype, including filamentation, was affected by any mutation. Together, these data predict that even partial pharmacological inhibition of Lro1p, Cho1p, and Lpt1p will limit C. albicans virulence through altering phospholipid composition.


Membranes Acyltransferases Phosphatidylserine synthase Heterozygous deletion Electrospray ionization tandem mass spectrometry Caenorhabditis elegans 



D.W. was supported by an Undergraduate Fellowship sponsored by the University of Michigan, Dearborn Office of Research and Sponsored Programs. P.O. received a seed grant from the same office. We thank Ruth Welti and Mary Roth for the mass spectrometry analysis performed at the Kansas Lipidomics Research Center (KLRC). Instrument acquisition and method development at the KLRC were supported by National Science Foundation (NSF) Grants MCB 0455318, MCB 0920663, DBI 0521587, DBI 1228622, Kansas IN BRE (National Institutes of Health Grant P20 RR16475 from the IN BRE program of the National Center for Research Resources), NSF EPS CoR Grant EPS-0236913, Kansas Technology Enterprise Corporation, and Kansas State University.

Compliance with Ethical Standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

11046_2019_320_MOESM1_ESM.pdf (91 kb)
Supplementary material 1 (PDF 90 kb)
11046_2019_320_MOESM2_ESM.pdf (53 kb)
Supplementary material 2 (PDF 52 kb)
11046_2019_320_MOESM3_ESM.pdf (118.9 mb)
Supplementary material 3 (PDF 121732 kb)
11046_2019_320_MOESM4_ESM.pdf (730 kb)
Supplementary material 4 (PDF 729 kb)


  1. 1.
    Pfaller MA, Andes DR, Diekema DJ, Horn DL, Reboli AC, Rotstein C, Franks B, Azie NE. Epidemiology and outcomes of invasive candidiasis due to non-albicans species of Candida in 2,496 patients: data from the Prospective Antifungal Therapy (PATH) registry 2004–2008. PLoS ONE. 2014;9:e101510.CrossRefGoogle Scholar
  2. 2.
    Zaoutis TE, Argon J, Chu J, Berlin JA, Walsh TJ, Feudtner C. The epidemiology and attributable outcomes of candidemia in adults and children hospitalized in the United States: a propensity analysis. Clin Infect Dis. 2005;41:1232–9.CrossRefGoogle Scholar
  3. 3.
    van Hal SJ, Chen SC-A, Sorrell TC, Ellis DH, Slavin M, Marriott DM. Support for the EUCAST and revised CLSI fluconazole clinical breakpoints by Sensititre® YeastOne® for Candida albicans: a prospective observational cohort study. J Antimicrob Chemother. 2014;69:2210–4.CrossRefGoogle Scholar
  4. 4.
    Hegazi M, Abdelkader A, Zaki M, El-Deek B. Characteristics and risk factors of candidemia in pediatric intensive care unit of a tertiary care children’s hospital in Egypt. J Infect Dev Ctries. 2014;8:624–34.CrossRefGoogle Scholar
  5. 5.
    Karacaer Z, Oncul O, Turhan V, Gorenek L, Ozyurt M. A surveillance of nosocomial candida infections: epidemiology and influences on mortalty in intensive care units. Pan Afr Med J. 2014;19:398.CrossRefGoogle Scholar
  6. 6.
    Tsai MH, Wang SH, Hsu JF, Lin LC, Chu SM, Huang HR, Chiang MC, Fu RH, Lu JJ, Huang YC. Clinical and molecular characteristics of bloodstream infections caused by Candida albicans in children from 2003 to 2011. Clin Microbiol Infect. 2015;21(1018):e1–8.Google Scholar
  7. 7.
    Alexander BD, Johnson MD, Pfeiffer CD, Jiménez-Ortigosa C, Catania J, Booker R, Castanheira M, Messer SA, Perlin DS, Pfaller MA. Increasing echinocandin resistance in Candida glabrata: clinical failure correlates with presence of FKS mutations and elevated minimum inhibitory concentrations. Clin Infect Dis. 2013;56:1724–32.CrossRefGoogle Scholar
  8. 8.
    Arendrup MC, Perlin DS. Echinocandin resistance: an emerging clinical problem? Curr Opin Infect Dis. 2014;27:484–92.CrossRefGoogle Scholar
  9. 9.
    Cleveland AA, Harrison LH, Farley MM, Hollick R, Stein B, Chiller TM, Lockhart SR, Park BJ. Declining incidence of candidemia and the shifting epidemiology of Candida resistance in two US metropolitan areas, 2008–2013: results from population-based surveillance. PLoS ONE. 2015;10:e0120452.CrossRefGoogle Scholar
  10. 10.
    Kinsky SC, Luse AA, Van Deenen LLM. Interactions of polyene antibiotics with natural and artificial membrane systems. Fed Proc. 1966;25:1503–10.Google Scholar
  11. 11.
    Gray KC, Palacios DS, Dailey I, Endo MM, Uno BE, Wilcock BC, Burke MD. Amphotericin primarily kills yeast by simply binding ergosterol. Proc Natl Acad Sci USA. 2012;109:2234–9.CrossRefGoogle Scholar
  12. 12.
    Sud IJ, Feingold DS. Heterogeneity of action mechanisms among antimycotic imidazoles. Antimicrob Agents Chemother. 1981;20:71–4.CrossRefGoogle Scholar
  13. 13.
    Yoshida Y, Aoyama Y, Takano H, Kato T. Stereoselective interaction of enantiomers of diniconazole, a fungicide, with purified P45014DM from yeast. Biochem Biophys Res Commun. 1986;137:513–9.CrossRefGoogle Scholar
  14. 14.
    Sreedhara Swamy KH, Sirsi M, Ramananda Rao GR. Studies on the mechanism of action of miconazole: effect of miconazole on respiration and cell permeability of Candida albicans. Antimicrob Agents Chemother. 1974;5:420–5.CrossRefGoogle Scholar
  15. 15.
    Vanden Bossche H, Marichal P, Willemsens G, Bellens D, Gorrens J, Roels I, Coene MC, Le Jeune L, Janssen PA. Saperconazole: a selective inhibitor of the cytochrome P-450-dependent ergosterol synthesis in Candida albicans, Aspergillus fumigatus and Trichophyton mentagrophytes. Mycoses. 1990;33:335–52.CrossRefGoogle Scholar
  16. 16.
    Kobayashi D, Kondo K, Uehara N, Otokozawa S, Tsuji N, Yagihashi A, Watanabe N. Endogenous reactive oxygen species is an important mediator of miconazole antifungal effect. Antimicrob Agents Chemother. 2002;46:3113–7.CrossRefGoogle Scholar
  17. 17.
    Thevissen K, Ayscough KR, Aerts AM, Du W, De Brucker K, Meert EM, Ausma J, Borgers M, Cammue BP, François IE. Miconazole induces changes in actin cytoskeleton prior to reactive oxygen species induction in yeast. J Biol Chem. 2007;282:21592–7.CrossRefGoogle Scholar
  18. 18.
    Onishi J, Meinz M, Thompson J, Curotto J, Dreikorn S, Rosenbach M, Douglas C, Abruzzo G, Flattery A, Kong L, Cabello A, Vicente F, Pelaez F, Diez MT, Martin I, Bills G, Giacobbe R, Dombrowski A, Schwartz R, Morris S, Harris G, Tsipouras A, Wilson K, Kurtz MB. Discovery of novel antifungal (1,3)-beta-d-glucan synthase inhibitors. Antimicrob Agents Chemother. 2000;44:368–77.CrossRefGoogle Scholar
  19. 19.
    Mann PA, McLellan CA, Koseoglu S, Si Q, Kuzmin E, Flattery A, Harris G, Sher X, Murgolo N, Wang H, Devito K, de Pedro N, Genilloud O, Kahn JN, Jiang B, Costanzo M, Boone C, Garlisi CG, Lindquist S, Roemer T. Chemical genomics-based antifungal drug discovery: targeting glycosylphosphatidylinositol (GPI) precursor biosynthesis. ACS Infect Dis. 2015;1:59–72.CrossRefGoogle Scholar
  20. 20.
    Mio T, Kokado M, Arisawa M, Yamada-Okabe H. Reduced virulence of Candida albicans mutants lacking the GNA1 gene encoding glucosamine-6-phosphate acetyltransferase. Microbiology. 2000;146:1753–8.CrossRefGoogle Scholar
  21. 21.
    Singh A, Prasad T, Kapoor K, Mandal A, Roth M, Welti PR. Phospholipidome of Candida: each species of Candida has distinctive phospholipid molecular species. OMICS. 2010;14:665–77.CrossRefGoogle Scholar
  22. 22.
    Capponi S, Freites JA, Tobias DJ, White SH. Interleaflet mixing and coupling in liquid-disordered phospholipid bilayers. Biochim Biophys Acta. 2016;1858:354–62.CrossRefGoogle Scholar
  23. 23.
    Domanska MK, Kiessling V, Tamm LK. Docking and fast fusion of synaptobrevin vesicles depends on the lipid compositions of the vesicle and the acceptor SNARE complex-containing target membrane. Biophys J. 2010;99:2936–46.CrossRefGoogle Scholar
  24. 24.
    Ramadurai S, Duurkens R, Krasnikov VV, Poolman B. Lateral diffusion of membrane proteins: consequences of hydrophobic mismatch and lipid composition. Biophys J. 2010;99:1482–9.CrossRefGoogle Scholar
  25. 25.
    Vitrac H, MacLean DM, Jayaraman V, Bogdanov M, Dowhan W. Dynamic membrane protein topological switching upon changes in phospholipid environment. Proc Natl Acad Sci. 2015;112:13874–9.CrossRefGoogle Scholar
  26. 26.
    Sugano K, Hamada H, Machida M, Ushio H. High throughput prediction of oral absorption: improvement of the composition of the lipid solution used in parallel artificial membrane permeation assay. J Biomol Screen. 2001;6:189–96.CrossRefGoogle Scholar
  27. 27.
    Wolf JM, Espadas J, Luque-Garcia J, Reynolds T, Casadevall A. Lipid biosynthetic genes affect Candida albicans extracellular vesicle morphology, cargo, and immunostimulatory properties. Eukaryot Cell. 2015;14:745–54.CrossRefGoogle Scholar
  28. 28.
    Davis SE, Hopke A, Minkin SC, Montedonico AE, Wheeler RT, Reynolds TB. Masking of β(1-3)-glucan in the cell wall of Candida albicans from detection by innate immune cells depends on phosphatidylserine. Infect Immun. 2014;82:4405–13.CrossRefGoogle Scholar
  29. 29.
    de Kroon AI, Rijken PJ, De Smet CH. Checks and balances in membrane phospholipid class and acyl chain homeostasis, the yeast perspective. Prog Lipid Res. 2013;52:374–94.CrossRefGoogle Scholar
  30. 30.
    Ayyash M, Algahmi A, Gillespie J, Oelkers P. Characterization of a lysophospholipid acyltransferase involved in membrane remodeling in Candida albicans. Biochim Biophys Acta. 2014;184:505–13.CrossRefGoogle Scholar
  31. 31.
    Chen Y-L, Montedonico AE, Kauffman S, Dunlap JR, Menn F-M, Reynolds TB. Phosphatidylserine synthase and phosphatidylserine decarboxylase are essential for cell wall integrity and virulence in Candida albicans. Mol Microbiol. 2010;75:1112–32.CrossRefGoogle Scholar
  32. 32.
    Jain S, Stanford N, Bhagwat N, Seiler B, Costanzo M, Boone C, Oelkers P. Identification of a novel lysophospholipid acyltransferase in Saccharomyces cerevisiae. J Biol Chem. 2007;282:30562–9.CrossRefGoogle Scholar
  33. 33.
    Riekhof WR, Wu J, Jones JL, Voelker DR. Identification and characterization of the major lysophosphatidylethanolamine acyltransferase in Saccharomyces cerevisiae. J Biol Chem. 2007;282:28344–52.CrossRefGoogle Scholar
  34. 34.
    Riekhof WR, Wu J, Gijón MA, Zarini S, Murphy RC, Voelker DR. Lysophosphatidylcholine metabolism in Saccharomyces cerevisiae: the role of P-type ATPases in transport and a broad specificity acyltransferase in acylation. J Biol Chem. 2007;282:36853–61.CrossRefGoogle Scholar
  35. 35.
    Benghezal M, Roubaty C, Veepuri V, Knudsen J, Conzelmann A. SLC1 and SLC4 encode partially redundant acyl-coenzyme A 1-acylglycerol-3-phosphate O-acyltransferases of budding yeast. J Biol Chem. 2007;282:30845–55.CrossRefGoogle Scholar
  36. 36.
    Chen Q, Kazachkov M, Zheng Z, Zou J. The yeast acylglycerol acyltransferase LCA1 is a key component of Lands cycle for phosphatidylcholine turnover. FEBS Lett. 2007;581:5511–6.CrossRefGoogle Scholar
  37. 37.
    Tamaki H, Shimada A, Ito Y, Ohya M, Takase J, Miyashita M, Miyagawa H, Nozaki H, Nakayama R, Kumagai H. LPT1 encodes a membrane-bound O-acyltransferase involved in the acylation of lysophospholipids in the yeast Saccharomyces cerevisiae. J Biol Chem. 2007;282:34288–98.CrossRefGoogle Scholar
  38. 38.
    Stahl U, Stalberg K, Stymne S, Ronne H. A family of eukaryotic lysophospholipid acyltransferases with broad specificity. FEBS Lett. 2008;582:305–9.CrossRefGoogle Scholar
  39. 39.
    Letts VA, Klig LS, Bae-Lee M, Carman GM, Henry SA. Isolation of the yeast structural gene for the membrane-associated enzyme phosphatidylserine synthase. Proc Natl Acad Sci. 1983;80:7279–83.CrossRefGoogle Scholar
  40. 40.
    Clancey CJ, Chang SC, Dowhan W. Cloning of a gene (PSD1) encoding phosphatidylserine decarboxylase from Saccharomyces cerevisiae by complementation of an Escherichia coli mutant. J Biol Chem. 1993;268:24580–90.Google Scholar
  41. 41.
    Rella A, Farnoud AM, Del Poeta M. Plasma membrane lipids and their role in fungal virulence. Prog Lipid Res. 2016;61:63–72.CrossRefGoogle Scholar
  42. 42.
    Trotter PJ, Pedretti J, Yates R, Voelker DR. Phosphatidylserine decarboxylase 2 of Saccharomyces cerevisiae. Cloning and mapping of the gene, heterologous expression, and creation of the null allele. J Biol Chem. 1995;270:6071–80.CrossRefGoogle Scholar
  43. 43.
    Mille C, Janbon G, Delplace F, Ibata-Ombetta S, Gaillardin C, Strecker G, Jouault T, Trinel PA, Poulain D. Inactivation of CaMIT1 inhibits Candida albicans phospholipomannan betamannosylation, reduces virulence, and alters cell wall protein. J Biol Chem. 2004;279:47952–60.CrossRefGoogle Scholar
  44. 44.
    Noble SM, French S, Kohn LA, Chen V, Johnson AD. Systematic screens of a Candida albicans homozygous deletion library decouple morphogenetic switching and pathogenicity. Nat Genet. 2010;42:590–8.CrossRefGoogle Scholar
  45. 45.
    Bishop AC, Ganguly S, Solis NV, Cooley BM, Jensen-Seaman MI, Filler SG, Mitchell AP, Patton-Vogt J. Glycerophosphocholine utilization by Candida albicans: role of the Git3 transporter in virulence. J Biol Chem. 2013;288:33939–52.CrossRefGoogle Scholar
  46. 46.
    Leidich SD, Ibrahim AS, Fu Y, Koul A, Jessup C, Vitullo J, Fonzi W, Mirbod F, Nakashima S, Nozawa Y, Ghannoum MA. Cloning and disruption of caPLB1, a phospholipase B gene involved in the pathogenicity of Candida albicans. J Biol Chem. 1998;273:26078–86.CrossRefGoogle Scholar
  47. 47.
    Gácser A, Stehr F, Kröger C, Kredics L, Schäfer W, Nosanchuk JD. Lipase 8 affects the pathogenesis of Candida albicans. Infect Immun. 2007;75:4710–8.CrossRefGoogle Scholar
  48. 48.
    Breger J, Fuchs BB, Aperis G, Moy TI, Ausubel FM, Mylonakis E. Antifungal chemical compounds identified using a C. elegans pathogenicity assay. PLoS Pathog. 2007;3:e18.CrossRefGoogle Scholar
  49. 49.
    Tampakakis E, Okoli I, Mylonakis EAC. Elegans-based, whole animal, in vivo screen for the identification of antifungal compounds. Nat Protoc. 2008;3:1925–31.CrossRefGoogle Scholar
  50. 50.
    Fiori A, Kucharíková S, Govaert G, Cammue BP, Thevissen K, Van Dijck P. The heat-induced molecular disaggregase Hsp104 of Candida albicans plays a role in biofilm formation and pathogenicity in a worm infection model. Eukaryot Cell. 2012;11:1012–20.CrossRefGoogle Scholar
  51. 51.
    Tan X, Fuchs BB, Wang Y, Chen W, Yuen GJ, Chen RB, Jayamani E, Anastassopoulou C, Pukkila-Worley R, Coleman JJ, Mylonakis E. The role of Candida albicans SPT20 in filamentation, biofilm formation and pathogenesis. PLoS ONE. 2014;9:e94468.CrossRefGoogle Scholar
  52. 52.
    Jain C, Pastor K, Gonzalez AY, Lorenz MC, Rao RP. The role of Candida albicans AP-1 protein against host derived ROS in in vivo models of infection. Virulence. 2013;4:67–76.CrossRefGoogle Scholar
  53. 53.
    Kim DH, Feinbaum R, Alloing G, Emerson FE, Garsin DA, Inoue H, Tanaka-Hino M, Hisamoto N, Matsumoto K, Tan MW, Ausubel FM. A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity. Science. 2002;297:623–6.CrossRefGoogle Scholar
  54. 54.
    Noble SM, Johnson AD. Strains and strategies for large-scale gene deletion studies of the diploid human fungal pathogen Candida albicans. Eukaryot Cell. 2005;4:298–309.CrossRefGoogle Scholar
  55. 55.
    Murad AMA, Lee PR, Broadbent ID, Barelle CJ, Brown AJP. CIp10, an efficient and convenient integrating vector for Candida albicans. Yeast. 2000;16:325–7.CrossRefGoogle Scholar
  56. 56.
    Needleman SB, Wunsch CD. A general method applicable to the search for similarities in the amino acid sequence of two proteins. J Mol Biol. 1970;48:443–53.CrossRefGoogle Scholar
  57. 57.
    McEntee CM, Hudson AP. Preparation of RNA from unspheroplasted yeast cells (Saccharomyces cerevisiae). Anal Biochem. 1989;176:303–6.CrossRefGoogle Scholar
  58. 58.
    Pfaffl MW. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001;29:e45.CrossRefGoogle Scholar
  59. 59.
    Pukkila-Worley R, Peleg AY, Tampakakis E, Mylonakis E. Candida albicans hyphal formation and virulence assessed using a Caenorhabditis elegans infection model. Eukaryot Cell. 2009;8:1750–8.CrossRefGoogle Scholar
  60. 60.
    Moy TI, Ball AR, Anklesaria Z, Casadei G, Lewis K, Ausubel FM. Identification of novel antimicrobials using a live-animal infection model. Proc Natl Acad Sci. 2006;103:10414–9.CrossRefGoogle Scholar
  61. 61.
    Laird NM, Ware JH. Random-effects model for longitudinal data. Biometrics. 1982;38:963–74.CrossRefGoogle Scholar
  62. 62.
    Davidian M, Giltinan DM. Nonlinear mixed effects models for repeated measurement data. London: Chapman and Hall; 1995.Google Scholar
  63. 63.
    Lattif AA, Mukherjee PK, Chandra J, Roth MR, Welti R, Rouabhia M, Ghannoum Ma. Lipidomics of Candida albicans biofilms reveals phase-dependent production of phospholipid molecular classes and role for lipid rafts in biofilm formation. Microbiology. 2011;157:3232–42.CrossRefGoogle Scholar
  64. 64.
    Aitchison J. The statistical analysis of compositional data., Monographs on statistics and applied probabilityNew York: Chapman and Hall; 1986.CrossRefGoogle Scholar
  65. 65.
    Johnson RA, Wichern DW. Applied multivariate statistical analysis. 6th ed. Hoboken: Pearson; 2007.Google Scholar
  66. 66.
    van den Boogaart GK, Tolosana-Delgado R. Analysing compositional data with R. Berlin: Springer; 2013.CrossRefGoogle Scholar
  67. 67.
    Liu H, Köhler J, Fink GR. Suppression of hyphal formation in Candida albicans by mutation of a STE12 homolog. Science. 1994;266:1723–6.CrossRefGoogle Scholar
  68. 68.
    CLSI. Reference method for broth dilution antifungal susceptibility testing of yeasts; approved standard, 3rd ed. CLSI document M27-A3. Wayne: CLSI; 2008.Google Scholar
  69. 69.
    Nagiec MM, Wells GB, Lester RL, Dickson RC. A suppressor gene that enables Saccharomyces cerevisiae to grow without making sphingolipids encodes a protein that resembles an Escherichia coli fatty acyltransferase. J Biol Chem. 1993;268:22156–63.Google Scholar
  70. 70.
    Oelkers P, Tinkelenberg A, Erdeniz N, Cromley D, Billheimer JT, Sturley SL. A lecithin cholesterol acyltransferase-like gene mediates diacylglycerol esterification in yeast. J Biol Chem. 2000;275:5609–12.CrossRefGoogle Scholar
  71. 71.
    Dahlqvist A, Ståhl U, Lenman M, Banas A, Lee M, Sandager L, Ronne H, Stymne S. Phospholipid:diacylglycerol acyltransferase: an enzyme that catalyzes the acyl-CoA-independent formation of triacylglycerol in yeast and plants. Proc Natl Acad Sci. 2000;97:6487–92.CrossRefGoogle Scholar
  72. 72.
    Voynova NS, Vionnet C, Ejsing CS, Conzelmann A. A novel pathway of ceramide metabolism in Saccharomyces cerevisiae. Biochem J. 2012;447:103–14.CrossRefGoogle Scholar
  73. 73.
    Chau AS, Mendrick CA, Sabatelli FJ, Loebenberg D, McNicholas PM. Application of real-time quantitative PCR to molecular analysis of Candida albicans strains exhibiting reduced susceptibility to azoles. Antimicrob Agents Chemother. 2004;48:2124–31.CrossRefGoogle Scholar
  74. 74.
    Cheng S, Clancy CJ, Checkley MA, Handfield M, Hillman JD, Progulske-Fox A, Lewin AS, Fidel PL, Nguyen MH. Identification of Candida albicans genes induced during thrush offers insight into pathogenesis. Mol Microbiol. 2003;48:1275–88.CrossRefGoogle Scholar
  75. 75.
    Lu H, Xiong J, Shang Q, Jiang Y, Cao Y. Roles of RPS41 in biofilm formation, virulence, and hydrogen peroxide sensitivity in Candida albicans. Curr Microbiol. 2016;72:783–7.CrossRefGoogle Scholar
  76. 76.
    Vanacloig-Pedros E, Bets-Plasencia C, Pascual-Ahuir A, Proft M. Coordinated gene regulation in the initial phase of salt stress adaptation. J Biol Chem. 2015;290:10163–75.CrossRefGoogle Scholar
  77. 77.
    Rao MJ, Srinivasan M, Rajasekharan R. Cell size is regulated by phospholipids and not by storage lipids in Saccharomyces cerevisiae. Curr Genet. 2018;64:1071–87.CrossRefGoogle Scholar
  78. 78.
    Pasrija R, Panwar SL, Prasad R. Multidrug transporters CaCdr1p and CaMdr1p of Candida albicans display different lipid specificities: both ergosterol and sphingolipids are essential for targeting of CaCdr1p to membrane rafts. Antimicrob Agents Chemother. 2008;52:694–704.CrossRefGoogle Scholar
  79. 79.
    Wang HX, Douglas LM, Veselá P, Rachel R, Malinsky J, Konopka JB. Eisosomes promote the ability of Sur7 to regulate plasma membrane organization in Candida albicans. Mol Biol Cell. 2016;27:1663–75.CrossRefGoogle Scholar
  80. 80.
    Pyle E, Kalli AC, Amillis S, Hall Z, Lau AM, Hanyaloglu AC, Diallinas G, Byrne B, Politis A. Structural lipids enable the formation of functional oligomers of the eukaryotic purine symporter UapA. Cell Chem Biol. 2018;25:840–8.CrossRefGoogle Scholar
  81. 81.
    Prakobphol A, Leffler H, Hoover CI, Fisher SJ. Palmitoyl carnitine, a lysophospholipase-transacylase inhibitor, prevents Candida adherence in vitro. FEMS Microbiol Lett. 1997;151:89–94.CrossRefGoogle Scholar
  82. 82.
    Min J, Lee YJ, Kim YA, Park HS, Han SY, Jhon GJ, Choi W. Lysophosphatidylcholine derived from deer antler extract suppresses hyphal transition in Candida albicans through MAP kinase pathway. Biochim Biophys Acta. 2001;1531:77–89.CrossRefGoogle Scholar
  83. 83.
    Smistad G, Nguyen NB, Hegna IK, Sande SA. Influence of liposomal formulation variables on the interaction with Candida albicans in biofilm; a multivariate approach. J Liposome Res. 2010;21:9–16.CrossRefGoogle Scholar
  84. 84.
    Trivedi A, Singhal GS, Prasad R. Effect of phosphatidylserine enrichment on amino acid transport in yeast. Biochim Biophys Acta. 1983;729:85–9.CrossRefGoogle Scholar
  85. 85.
    Chakravarthy MV, Lodhi IJ, Yin L, Malapaka RR, Xu HE, Turk J, Semenkovich CF. Identification of a physiologically relevant endogenous ligand for PPARalpha in liver. Cell. 2009;138:476–88.CrossRefGoogle Scholar
  86. 86.
    Cassilly CD, Farmer AT, Montedonico AE, Smith TK, Campagna SR, Reynolds TB. Role of phosphatidylserine synthase in shaping the phospholipidome of Candida albicans. FEMS Yeast Res. 2017;17:fox007.CrossRefGoogle Scholar
  87. 87.
    McLean J, Fielding C, Drayna D, Dieplinger H, Baer B, Kohr W, Henzel W, Lawn R. Cloning and expression of human lecithin-cholesterol acyltransferase cDNA. Proc Natl Acad Sci. 1986;83:2335–9.CrossRefGoogle Scholar
  88. 88.
    Taniyama Y, Shibata S, Kita S, Horikoshi K, Fuse H, Shirafuji H, Sumino Y, Fujino M. Cloning and expression of a novel lysophospholipase which structurally resembles lecithin cholesterol acyltransferase. Biochem Biophys Res Commun. 1999;257:50–6.CrossRefGoogle Scholar
  89. 89.
    Oldoni F, Baldassarre D, Castelnuovo S, Ossoli A, Amato M, van Capelleveen J, Hovingh GK, de Groot E, Bochem A, Simonelli S, Barbieri S, Veglia F, Franceschini G, Kuivenhoven JA, Holleboom AG, Calabresi L. Complete and partial LCAT deficiency are differentially associated with atherosclerosis. Circulation. 2018;138:1000–7.CrossRefGoogle Scholar
  90. 90.
    Hiraoka M, Abe A, Shayman JA. Cloning and characterization of a lysosomal phospholipase A2, 1-O-acylceramide synthase. J Biol Chem. 2002;277:10090–9.CrossRefGoogle Scholar
  91. 91.
    Taniyama Y, Fuse H, Satomi T, Tozawa R, Yasuhara Y, Shimakawa K, Shibata S, Hattori M, Nakata M, Taketomi S. Loss of lysophospholipase 3 increases atherosclerosis in apolipoprotein E-deficient mice. Biochem Biophys Res Commun. 2005;330:104–10.CrossRefGoogle Scholar
  92. 92.
    Zhao Y, Chen YQ, Bonacci TM, Bredt DS, Li S, Bensch WR, Moller DE, Kowala M, Konrad RJ, Cao G. Identification and characterization of a major liver lysophosphatidylcholine acyltransferase. J Biol Chem. 2008;283:8258–65.CrossRefGoogle Scholar
  93. 93.
    Kazachkov M, Chen Q, Wang L, Zou J. Substrate preferences of a lysophosphatidylcholine acyltransferase highlight its role in phospholipid remodeling. Lipids. 2008;43:895–902.CrossRefGoogle Scholar
  94. 94.
    Jain S, Zhang X, Khandelwal PK, Saunders AS, Cummings BS, Oelkers P. Characterization of a novel human lysophospholipid acyltransferase (LPCAT3). J Lipid Res. 2009;50:1563–70.CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of Natural SciencesUniversity of Michigan-DearbornDearbornUSA
  2. 2.Department of Mathematics and StatisticsUniversity of Michigan-DearbornDearbornUSA

Personalised recommendations