Abstract
Candida albicans is an opportunistic human fungal pathogen that causes life-threatening systemic infections, as well as oral mucosal infections. Phospholipids are crucial for pathogenesis in C. albicans, as disruption of phosphatidylserine (PS) and phosphatidylethanolamine (PE) biosynthesis within the cytidine diphosphate diacylglycerol (CDP-DAG) pathway causes avirulence in a mouse model of systemic infection. The synthesis of PE by this pathway plays a crucial role in virulence, but it was unknown if downstream conversion of PE to phosphatidylcholine (PC) is required for pathogenicity. Therefore, the enzymes responsible for methylating PE to PC, Pem1 and Pem2, were disrupted. The resulting pem1Δ/Δ pem2Δ/Δ mutant was not less virulent in mice, but rather hypervirulent. Since the pem1Δ/Δ pem2Δ/Δ mutant accumulated PE, this led to the hypothesis that increased PE synthesis increases virulence. To test this, the alternative Kennedy pathway for PE/PC synthesis was exploited. This pathway makes PE and PC from exogenous ethanolamine and choline, respectively, using three enzymatic steps. In contrast to Saccharomyces cerevisiae, C. albicans was found to use one enzyme, Ept1, for the final enzymatic step (ethanolamine/cholinephosphotr...Continue Reading
References
Apr 1, 1992·The Biochemical Journal·M HouwelingL M van Golde
Apr 1, 1986·Journal of Bacteriology·J NikawaS Yamashita
Jan 1, 1984·Molecular & General Genetics : MGG·A M GillumD R Kirsch
Apr 14, 1994·Biochimica Et Biophysica Acta·J H Exton
Jul 25, 1993·Biochimica Et Biophysica Acta·H G Bauernschmitt, R K Kinne
Feb 1, 1993·Current Genetics·W PreitschopfS D Kohlwein
Mar 1, 1993·Neurochemistry International·J KleinK Löffelholz
Nov 18, 2000·The Journal of Biological Chemistry·S R DowdJ L Patton-Vogt
Jun 21, 2002·Methods in Enzymology·Cora Styles
Mar 5, 2003·The Journal of Antimicrobial Chemotherapy·Valérie Letscher-Bru, Raoul Herbrecht
Oct 12, 2004·Gene·Oliver ReussJoachim Morschhäuser
Jan 18, 2005·Clinical Microbiology Reviews·Pranab K MukherjeeMahmoud A Ghannoum
Jul 27, 2005·The Journal of Nutritional Biochemistry·Yeşim Ozarda IlcolIsmail H Ulus
Jan 10, 2006·Eukaryotic Cell·Raquel Martinez-LopezScott G Filler
Feb 13, 2008·Infection and Immunity·Ying-Lien ChenTodd B Reynolds
Dec 17, 2008·International Journal of Antimicrobial Agents·Emilio Bouza, Patricia Muñoz
Jun 27, 2009·Molecular Microbiology·Federica GibelliniTerry K Smith
Oct 21, 2009·The Journal of Biological Chemistry·J Pedro Fernández-MurrayChristopher R McMaster
Feb 6, 2010·Molecular Microbiology·Ying-Lien ChenTodd B Reynolds
May 27, 2010·IUBMB Life·Federica Gibellini, Terry K Smith
Aug 24, 2010·Omics : a Journal of Integrative Biology·Ashutosh SinghRajendra Prasad
May 7, 2011·Journal of Oral Microbiology·David Williams, Michael Lewis
Feb 22, 2012·Genetics·Susan A HenryGeorge M Carman
May 2, 2013·Progress in Lipid Research·Anton I P M de KroonCedric H De Smet
Jan 1, 2012·ISRN Microbiology·M Anaul KabirZulfiqar Ahmad
Oct 12, 2013·The Journal of Biological Chemistry·Andrew C BishopJana Patton-Vogt
Dec 5, 2013·The Journal of Biological Chemistry·Sahar HasimMark A Wilson
Sep 27, 2014·The Journal of Biological Chemistry·Beth A SurlowJana Patton-Vogt
Jun 3, 2015·Mycoses·Maurizio SanguinettiCornelia Lass-Flörl
Feb 6, 2017·FEMS Yeast Research·Chelsi D CassillyTodd B Reynolds
Apr 27, 2017·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Susana Suárez-GarcíaManuel Suárez
Citations
Feb 28, 2020·Journal of Fungi·Tyler G NormileMaurizio Del Poeta
Dec 4, 2019·Infection and Immunity·Robert N TamsTodd B Reynolds
Nov 10, 2020·Frontiers in Immunology·Yue HuZhiyue Lv
Jul 22, 2021·Cell Reports·Sabrina JenullKarl Kuchler
Aug 26, 2021·PLoS Pathogens·Andrew S WagnerTodd B Reynolds
Aug 24, 2021·Journal of Applied Microbiology·Sandeep HansSaif Hameed