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In this study, we have specifically blocked a key step of sphingolipid (SL) biosynthesis in Candida glabrata by disruption of the orthologs of ScIpt1 and ScSkn1. Based on their close homology with S. cerevisiae counterparts, the proteins are predicted to catalyze the addition of a phosphorylinositol group onto mannosyl inositolphosphoryl ceramide (MIPC) to form mannosyl diinositolphosphoryl ceramide (M(IP)2C), which accounts for the majority of complex SL structures in S. cerevisiae membranes. High throughput lipidome analysis confirmed the accumulation of MIPC structures in ΔCgipt1 and ΔCgskn1 cells, albeit to lesser extent in the latter. Noticeably, ΔCgipt1 cells showed an increased susceptibility to azoles; however, ΔCgskn1 cells showed no significant changes in the drug susceptibility profiles. Interestingly, the azole susceptible phenotype of ΔCgipt1 cells seems to be independent of the ergosterol content. ΔCgipt1 cells displayed altered lipid homeostasis, increased membrane fluidity as well as high diffusion of radiolabeled fluconazole (3H-FLC), which could together influence the azole susceptibility of C. glabrata. Furthermore, in vivo experiments also confirmed compromised virulence of the ΔCgipt1 strain. Contrarily, specific functions of CgSkn1 remain unclear. [ABSTRACT FROM AUTHOR]

The present study is an attempt to determine the lipid composition of Candida auris and to highlight if the changes in lipids can be correlated to high drug resistance encountered in C. auris. For this, the comparative lipidomics landscape between drug-susceptible (CBS10913T) and a resistant hospital isolate (NCCPF_470033) of C. auris was determined by employing high throughput mass spectrometry. All major groups of phosphoglycerides (PGL), sphingolipids, sterols, diacylglycerols (DAG) and triacylglycerols (TAG), were quantitated along with their molecular lipid species. Our analyses highlighted several key changes where the NCCPF_470033 showed an increase in PGL content, specifically phosphatidylcholine, phosphatidylglycerol, phosphatidylserine, phosphatidylinositol, and phosphatidylethanolamine; odd chain containing lipids and accumulation of 16:1-DAG and 16:0-DAG; depletion of 18:1-TAG and 18:0-TAG. The landscape of molecular species displayed a distinct imprint between isolates. For example, the levels of unsaturated PGLs, contributed by both odd and even-chain fatty acyls were higher in resistant NCCPF_470033 isolate, resulting in a higher unsaturation index. Notwithstanding, several commonalities of lipid compositional changes between resistant C. auris and other Candida spp. the study could also identify distinguishable changes in specific lipid species in C. auris. Together, the data highlights the modulation of membrane lipid homeostasis associated with drug-resistant phenotype of C. auris. [ABSTRACT FROM AUTHOR]

ATP-binding cassette (ABC) is one of the two major superfamilies of transporters present across the evolutionary scale. ABC superfamily members came to prominence due to their ability to extrude broad spectrum of substrates and to confer multi drug resistance (MDR). Overexpression of some ABC transporters in clinical isolates of Candida species was attributed to the development of MDR phenotypes. Among Candida species, Candida glabrata is an emerging drug resistant species in human fungal infections. A comprehensive analysis of such proteins in C. glabrata is required to untangle their role not only in MDR but also in other biological processes. Bioinformatic analysis of proteins encoded by genome of human pathogenic yeast C. glabrata identified 25 putative ABC protein coding genes. On the basis of phylogenetic analysis, domain organization and nomenclature adopted by the Human Genome Organization (HUGO) scheme, these proteins were categorized into six subfamilies such as Pleiotropic Drug Resistance (PDR)/ABCG, Multi Drug Resistance (MDR)/ABCB, Multi Drug Resistance associated Protein (MRP)/ABCC, Adrenoleukodystrophy protein (ALDp)/ABCD, RNase L Inhibitor (RLI)/ABCE and Elongation Factor 3 (EF3)/ABCF. Among these, only 18 ABC proteins contained transmembrane domains (TMDs) and were grouped as membrane proteins, predominantly belonging to PDR, MDR, MRP, and ALDp subfamilies. A comparative phylogenetic analysis of these ABC proteins with other yeast species revealed their orthologous relationship and pointed towards their conserved functions. Quantitative real time PCR (qRT-PCR) analysis of putative membrane localized ABC protein encoding genes of C. glabrata confirmed their basal expression and showed variable transcriptional response towards antimycotic drugs. This study presents first comprehensive overview of ABC superfamily proteins of a human fungal pathogen C. glabrata, which is expected to provide an important platform for in depth analysis of their physiological relevance in cellular processes and drug resistance. [ABSTRACT FROM AUTHOR]

This paper addresses the optimal allotment of ground station support time to low orbit (LEO) spacecraft with clashing visibilities. Orbiting once every 100 or so minutes at a 800 km height, LEOs now form a critical infrastructure for natural resource management, rescue, crop yield estimation, flood control, communication, and space research and travel support worldwide. This problem is a generalization of the classical product mix problem in which 'production quantities' (representing support times) must be determined so as to maximize total profits to the enterprise while subject to a multitude of constraints. The problem is NP-complete. The present methodology exploits the structure of the profit function and constraints and invokes meta-heuristic methods to determine the optimum allocation. The paper concludes with the solution of a practical satellite support optimization problem routinely faced by mission managers. An important spin-off of this work is that it can enable the decision maker to also determine optimal ground station locations and support capability deployment in widely diverse scenarios. [ABSTRACT FROM AUTHOR]