Mass spectrometry based untargeted lipidomics reveals new compositional insights into membrane dynamics of Candida albicans under magnesium deprivation.

Abstract

AIMS\nThere is growing appreciation in adopting new approaches to disrupt multidrug resistance in human fungal pathogen, Candida albicans. The plasma membrane of C. albicans is comprised of potential lipid moieties that contributes toward the survival of pathogen and could be utilized as antifungal targets. Considering promising applications of developments in mass spectrometry (MS) based lipidomics technology, the aim of the study is to analyze lipidome profile and expose lipid dependent changes in response to Mg deprivation.\n\n\nMETHODS AND RESULTS\nWe found that both phosphatidylcholine (PC) and lysophosphatidylcholine (LysoPC) were decreased. Increased flip (inward translocation) in the fluorophore labeled NBD-PC ascribed to enhanced PC specific flippase activity. Furthermore, decrease in phosphatidylethanolamine (PE) leading to altered membrane fluidity and loss of cellular material was prominent. Additionally, we observed decreased phosphatidylglycerol (PG) and phosphatidylinositol (PI) leading to genotoxic stress. Besides, we could detect enhanced levels of phosphatidylserine (PS), Diacylglycerol (DAG) and triacylglycerides (TAG). The altered gene expressions of lipid biosynthetic pathway by RT-PCR correlated with the lipidome profile. Lastly we explored abrogated ionic (Na+ and K+ ) transport across the plasma membrane.\n\n\nCONCLUSIONS\nWe propose that C. albicans exposed to Mg deprivation could reorganize plasma membrane (lipid species, membrane fluidity and ionic transport) and possibly redirected carbon flux to store energy in TAGs as an adaptive stress response. This work unravels several vulnerable targets governing lipid metabolism in C. albicans and pave way towards better antifungal strategies.\n\n\nSIGNIFICANCE AND IMPACT OF THE STUDY\nThis study demonstrates that magnesium availability is important when one considers dissecting drug resistance mechanisms in Candida albicans. Through mass spectrometry (MS) based lipidomics technology, the study analyze lipidome profile and exposes lipid dependent changes that are vulnerable to magnesium availability and presents an opportunity to employ this new information in improving treatment strategies.