title: Lipidomics and in vitro azole resistance in Candida albicans.
abstract: We have shown earlier that fluconazole (FLC) stress induces global changes in the lipidome of Candida albicans in clinically adapted isolates. However, several laboratories have developed adapted in vitro FLC resistant strains of C. albicans to study azole resistance mechanisms. This study aimed to identify the lipid changes associated with FLC resistance in these in vitro adapted isolates. Using comparative lipidomics and principal component and discriminant analyses, we observed gradual changes in several lipid classes and molecular species upon FLC exposure of in vitro resistant C. albicans strains. Although the lipid imprint of FLC in vitro resistant isolates was very distinct from that of clinical isolates of C. albicans, the overall changes in lipid class compositions were similar in both cases. For example, an increased sterol content and depleted sphingolipid levels were the salient features of FLC resistance in both conditions. Taken together, it appears that the overall cellular lipid homeostasis is a critical factor in the observed FLC resistance and in handling FLC stress in both clinical and laboratory situations. The new observations reported herein have implications for more efficacious antifungal drug development as well as understanding host-infectious agent interactions in postgenomics microbiology practice.
authors: Membrane Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
authors: Ashutosh
authors: A
authors: Singh
authors: Kaushal Kumar
authors: KK
authors: Mahto
authors: Rajendra
authors: R
authors: Prasad
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D025141:Drug Resistance, Fungal; D005227:Fatty Acids / Q000378:metabolism; D020404:Glycerophospholipids / Q000378:metabolism; D050356:Lipid Metabolism; D025341:Principal Component Analysis; D013261:Sterols / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D005227:Fatty Acids; D020404:Glycerophospholipids; D013261:Sterols
references: Antimicrob Agents Chemother. 2002 Dec;46(12):3695-705
references: 12435664
references: Curr Opin Infect Dis. 2002 Dec;15(6):569-74
references: 12821832
references: Biochim Biophys Acta. 2002 Jul 18;1587(2-3):240-8
references: 12084466
references: Antimicrob Agents Chemother. 1996 Dec;40(12):2835-41
references: 9124851
references: Biochem Soc Trans. 2005 Nov;33(Pt 5):1219-23
references: 16246085
references: Int J Antimicrob Agents. 2006 May;27(5):359-66
references: 16647248
references: PLoS One. 2011 Apr 29;6(4):e19266
references: 21559392
references: Proc Natl Acad Sci U S A. 1994 Oct 25;91(22):10635-9
references: 7938005
references: Trends Cell Biol. 2006 Oct;16(10):538-46
references: 16962778
references: Antimicrob Agents Chemother. 2002 Apr;46(4):1046-52
references: 11897588
references: Antimicrob Agents Chemother. 2008 Feb;52(2):694-704
references: 18056285
references: Can J Biochem Physiol. 1959 Aug;37(8):911-7
references: 13671378
references: J Bacteriol. 2000 Mar;182(6):1515-22
references: 10692355
references: Mol Microbiol. 2011 Feb;79(4):968-89
references: 21299651
references: J Antimicrob Chemother. 2005 Sep;56 Suppl 1:i5-i11
references: 16120635
references: Methods Mol Biol. 1996;53:123-31
references: 8924974
references: Clin Microbiol Rev. 2007 Jan;20(1):133-63
references: 17223626
references: Nat Rev Mol Cell Biol. 2010 Aug;11(8):593-8
references: 20606693
references: Biochem J. 2010 Sep 15;430(3):519-29
references: 20604746
references: Front Biosci (Elite Ed). 2012 Jan 01;4:1195-209
references: 22201946
references: FEMS Yeast Res. 2009 Oct;9(7):1029-50
references: 19799636
references: OMICS. 2010 Dec;14(6):665-77
references: 20726778
references: Antimicrob Agents Chemother. 2004 May;48(5):1778-87
references: 15105135
references: Eukaryot Cell. 2011 Nov;10(11):1376-83
references: 21926328
references: Mol Microbiol. 2010 Mar;75(5):1112-32
references: 20132453
references: Curr Fungal Infect Rep. 2009 Sep 1;3(3):163-169
references: 20161440
references: Int Rev Cytol. 2005;242:215-48
references: 15598470
references: Antimicrob Agents Chemother. 1999 Jul;43(7):1621-30
references: 10390213
references: Nat Biotechnol. 2008 Mar;26(3):303-4
references: 18327243
references: Clin Microbiol Rev. 1998 Apr;11(2):382-402
references: 9564569
references: J Lipid Res. 2010 May;51(5):1218-27
references: 19965589
references: PLoS One. 2012;7(6):e39812
references: 22761908
references: PLoS Pathog. 2010 Jun 03;6(6):e1000939
references: 20532216