Original Research ARTICLE
A targeted mass spectrometric analysis reveals the presence of a reduced but dynamic sphingolipid metabolic pathway in an ancient protozoan, Giardia lamblia
- 1The University of Texas at El Paso, United States
Giardia lamblia, a single-celled eukaryote, colonizes and thrives in the small intestine of humans. Because of its compact and reduced genome, Giardia has adapted a “minimalistic” life style, as it becomes dependent on available resources of the small intestine. Because Giardia expresses fewer sphingolipid (SL) genes—and glycosphingolipids are critical for encystation—we investigated the SL metabolic cycle in this parasite. A tandem mass spectrometry (MS/MS) analysis reveals that major SLs in Giardia include sphingomyelins, sphingoid bases, ceramides, and glycosylceramides. Many of these lipids are obtained by Giardia from the growth medium, remodeled at their fatty acyl chains and end up in the spent medium. For instance, ceramide-1-phosphate, a proinflammatory molecule that is not present in the culture medium, is generated from sphingosine (abundant in the culture medium) possibly by remodeling reactions. It is then subsequently released into the spent medium. Thus, the secretion of ceramide-1-phospate and other SL derivatives by Giardia could be associated with inflammatory bowel disease observed in acute giardiasis. Additionally, we found that the levels of SLs increase in encysting Giardia and are differentially regulated throughout the encystation cycle. We propose that SL metabolism is important for this parasite and, could serve as potential targets for developing novel anti-giardial agents.
Keywords: ceramide, cyst, Encystation, Giardia, Glycosphingolipid, Lipid, Mass Spectrometry, Sphingolipids, Sphingomyelin, Trophozoites
Received: 03 Feb 2019;
Accepted: 24 Jun 2019.
Edited by:Tomoyoshi Nozaki, Graduate School of Medicine and Faculty of Medicine, University of Tokyo, Japan
Reviewed by:Giuseppe Palmisano, University of São Paulo, Brazil
Iris Bruchhaus, Bernhard-Nocht-Institut für Tropenmedizin (BMITM), Germany
Hugo D. Lujan, National Council for Scientific and Technical Research (CONICET), Argentina
Copyright: © 2019 Duarte, Chatterjee, Almeida and Das. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Prof. Siddhartha Das, The University of Texas at El Paso, El Paso, 79968, Texas, United States, firstname.lastname@example.org