ABSTRACT
Ras signaling and glycosylphosphatidylinositol (GPI) biosynthesis are mutually inhibitory in S. cerevisiae (Sc). The inhibition is mediated via an interaction of yeast Ras2 with the Eri1 subunit of its GPI-N-acetylglucosaminyl transferase (GPI-GnT), the enzyme catalyzing the very first GPI biosynthetic step. In contrast, Ras signaling and GPI biosynthesis in C. albicans (Ca) are mutually activated and together control the virulence traits of the human fungal pathogen. What might be the role of Eri1 in this pathogen? The present manuscript addresses this question while simultaneously characterizing the cellular role of CaEri1. It is either nonessential or required at very low levels for cell viability in C. albicans. Severe depletion of CaEri1 results in reduced GPI biosynthesis and cell wall defects. It also produces hyperfilamentation phenotypes in Spider medium as well as in bicarbonate medium containing 5% CO2, suggesting that both the Ras-dependent and Ras-independent cAMP-PKA pathways for hyphal morphogenesis are activated in these cells. Pull-down and acceptor-photobleaching FRET experiments suggest that CaEri1 does not directly interact with CaRas1 but does so through CaGpi2, another GPI-GnT subunit. We showed previously that CaGpi2 is downstream of CaEri1 in cross talk with CaRas1 and for Ras-dependent hyphal morphogenesis. Here we show that CaEri1 is downstream of all GPI-GnT subunits in inhibiting Ras-independent filamentation. CaERI1 also participates in intersubunit transcriptional cross talk within the GPI-GnT, a feature unique to C. albicans. Virulence studies using G. mellonella larvae show that a heterozygous strain of CaERI1 is better cleared by the host and is attenuated in virulence.
ABSTRACT
Drug delivery systems (DDS) based on nanocarriers are designed to transport therapeutic agents to specific areas of the body where they are required to exhibit pharmacodynamic effect. These agents rely on an appropriate carrier to protect them from rapid degradation or clearance and enhance their concentration in target tissues. Spanlastics, an elastic, deformable surfactant-based nanovesicles have the potential to be used as a drug delivery vehicle for wide array of drug molecules. Spanlastics are formed by the self-association of non-ionic surfactants and edge activators in an aqueous phase and have gained attention as promising drug carriers due to their biodegradable, biocompatible, and non-immunogenic structure. In recent years, numerous scientific journals have published research articles exploring the potential of spanlastics to serve as a DDS for various types of drugs as they offer targeted delivery and regulated release of the drugs. Following brief introduction to spanlastics, their structure and methods of preparation, this review focuses on the delivery of various drugs using spanlastics as a carrier via various routes viz. topical, transdermal, ototopical, ocular, oral and nasal. Work carried out by various researchers by employing spanlastics as a carrier for enhancing therapeutic activity of different moieties has been discussed in detail.