Elucidating the binding specificity of interactive compounds targeting ATP-binding cassette subfamily G member 2 (ABCG2).

The ATP-binding cassette transporter superfamily plays a pivotal role in cellular detoxification and drug efflux. ATP-binding cassette subfamily G member 2 (ABCG2) referred to as the Breast cancer resistance protein has emerged as a key member involved in multidrug resistance displayed by cancer cells. Understanding the molecular basis of substrate and inhibitor recognition, and binding within the transmembrane domain of ABCG2 is crucial for the development of effective therapeutic strategies.

A Comprehensive Analysis of the Lipidomic Signatures in .

Certain species of Mucorales have been identified as causative agents of mucormycosis, a rare yet often lethal fungal infection. Notably, these fungi exhibit intrinsic resistance to common azole drugs, which target lipids. Given the pivotal role of lipids in drug resistance and their contribution to innate resistance to azoles, this study provides a comprehensive overview of key lipid classes, including sphingolipids (SLs), glycerophospholipids (GPLs), and sterols, in 99-880, a well-characterized reference strain among Mucorales.

Insights into the Theranostic Activity of Nonoxido V: Lysosome-Targeted Anticancer Metallodrugs.

Developing new anticancer agents can be useful, with the ability to diagnose and treat cancer worldwide. Previously, we focused on examining the effects of nonoxidovanadium(IV) complexes on insulin mimetic and cytotoxicity activity. In this study, in addition to the cytotoxic activity, we evaluated their bioimaging properties.

Bacterial cellulose microfilament biochar-architectured chitosan/polyethyleneimine beads for enhanced tetracycline and metronidazole adsorption.

This study investigates the potential applications of incorporating 2D bacterial cellulose microfibers (BCM) biochar into chitosan/polyethyleneimine beads as a semi-natural sorbent for the efficient removal of tetracycline (TET) and metronidazole (MET) antibiotics. Batch adsorption experiments and characterization techniques evaluate removal performance and synthesized adsorbent properties. The adsorbent eliminated 99.

Comprehensive analysis of cationic dye removal from synthetic and industrial wastewater using a semi-natural curcumin grafted biochar/poly acrylic acid composite hydrogel.

Polymer composites offer a tailored framework as an exceptional candidate for water treatment due to their tunable chemical structure, porous 3D architecture, physiochemical stability, accessibility, pH-sensitivity and ease of use. In this study, curcumin-engineered biochar is embedded into a cross-linked polyacrylic acid hydrogel matrix using polymerization for developing a semi-natural adsorbent for the removal of cationic dye from an aqueous solution. The physicochemical features of the generated composite hydrogel are significantly influenced by the implementation of curcumin-grafted biochar into the polyacrylic acid substrate.

Purification and characterization of Cdr1, the drug-efflux pump conferring azole resistance in Candida species.

Candida albicans and C. glabrata express exporters of the ATP-binding cassette (ABC) superfamily and address them to their plasma membrane to expel azole antifungals, which cancels out their action and allows the yeast to become multidrug resistant (MDR). In a way to understand this mechanism of defense, we describe the purification and characterization of Cdr1, the membrane ABC exporter mainly responsible for such phenotype in both species.

Bacterial cellulose microfiber reinforced hollow chitosan beads decorated with cross-linked melamine plates for the removal of the Congo red.

In this epoch, the disposal of multipollutant wastewater inevitably compromises life on Earth. In this study, the inclusion of Bacterial cellulose microfilaments reinforced chitosan adorned with melamine 2D plates creates a unique 3D bead structure for anionic dye removal. The establishment of an imine network between melamine and chitosan, along with the quantity of inter- and intra‑hydrogen bonds, boosts the specific surface area to 106.

Structure, function, and inhibition of catalytically asymmetric ABC transporters: Lessons from the PDR subfamily.

ATP-binding cassette (ABC) superfamily comprises a large group of ubiquitous transmembrane proteins that play a crucial role in transporting a diverse spectrum of substrates across cellular membranes. They participate in a wide array of physiological and pathological processes including nutrient uptake, antigen presentation, toxin elimination, and drug resistance in cancer and microbial cells. ABC transporters couple ATP binding and hydrolysis to undergo conformational changes allowing substrate translocation.

A Series of Non-Oxido V Complexes of Dibasic ONS Donor Ligands: Solution Stability, Chemical Transformations, Protein Interactions, and Antiproliferative Activity.

A series of mononuclear non-oxido vanadium(IV) complexes, [V(L)] (), featuring tridentate bi-negative ONS chelating S-alkyl/aryl-substituted dithiocarbazate ligands HL, are reported. All the synthesized non-oxido V compounds are characterized by elemental analysis, spectroscopy (IR, UV-vis, and EPR), ESI-MS, as well as electrochemical techniques (cyclic voltammetry). Single-crystal X-ray diffraction studies of - reveal that the mononuclear non-oxido V complexes show distorted octahedral ( and ) or trigonal prismatic () arrangement around the non-oxido V center.

Draft Genome Sequence of the Fluconazole-Resistant Yarrowia lipolytica Clinical Isolate CBS 18115.

Yarrowia lipolytica is a nonconventional yeast of industrial interest that can sometimes act as an opportunistic pathogen and is responsible for invasive fungal infections. We report the draft genome sequence of the fluconazole-resistant strain CBS 18115, which was isolated from a blood culture. The Y132F substitution in , which was previously described in fluconazole-resistant isolates, was identified.

Directed Evolution Detects Supernumerary Centric Chromosomes Conferring Resistance to Azoles in Candida auris.

Candida auris exhibits resistance to multiple antifungal drug classes and sterilization agents, posing threats to the immunocompromised worldwide. Among the four major geographical clades, the East Asian clade 2 isolates of C. auris are mostly drug susceptible.

Draft Genome Sequence of the Fluconazole-Resistant Candida palmioleophila Clinical Isolate CBS 18098.

Candida palmioleophila belongs to the Saccharomycetales. This opportunistic yeast which has been associated with invasive infections in human and animals, warrants a specific attention as it is frequently misidentified and display reduced susceptibility to fluconazole. Here, we report the first draft genome of C.

Genomic landscape of the DHA1 family in Candida auris and mapping substrate repertoire of CauMdr1.

The last decade has witnessed the rise of an extremely threatening healthcare-associated multidrug-resistant non-albicans Candida (NAC) species, Candida auris. Since besides target alterations, efflux mechanisms contribute maximally to antifungal resistance, it is imperative to investigate their contributions in this pathogen. Of note, within the major facilitator superfamily (MFS) of efflux pumps, drug/H antiporter family 1 (DHA1) has been established as a predominant contributor towards xenobiotic efflux.

Inositol Phosphoryl Transferase, Ipt1, Is a Critical Determinant of Azole Resistance and Virulence Phenotypes in .

In this study, we have specifically blocked a key step of sphingolipid (SL) biosynthesis in by disruption of the orthologs of ScIpt1 and ScSkn1. Based on their close homology with 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)C), which accounts for the majority of complex SL structures in membranes. High throughput lipidome analysis confirmed the accumulation of MIPC structures in and cells, albeit to lesser extent in the latter.

Production and Purification of a GFP-Tagged ABC Transporter CaCdr1p.

The production and purification are the first steps required in any functional or structural study of a protein of interest. In the case of membrane proteins, these tasks can be difficult due to low expression levels and the necessity to extract them from their membrane environment. This chapter describes a convenient method based on GFP tagged to the membrane protein to facilitates these steps.

Bioinformatic Identification of ABC Transporters in Candida auris.

Antifungal resistance mediated by overexpression of ABC transporters is one of the primary roadblocks to effective therapy against Candida infections. Thus, identification and characterization of the ABC transporter repertoire in Candida species are of high relevance. The method described in the chapter is based on our previously developed bioinformatic pipeline for identification of ABC proteins in Candida species.

Genome-wide analysis of PTR transporters in Candida species and their functional characterization in Candida auris.

The peptide transport (PTR) or proton-dependent oligopeptide transporter (POT) family exploits the inwardly directed proton motive force to facilitate the cellular uptake of di/tripeptides. Interestingly, some representatives are also shown to import peptide-based antifungals in certain Candida species. Thus, the identification and characterization of PTR transporters serve as an essential first step for their potential usage as antifungal peptide uptake systems.

Spontaneous Suppressors against Debilitating Transmembrane Mutants of Mdr1 Disclose Novel Interdomain Communication via Signature Motifs of the Major Facilitator Superfamily.

The Major Facilitator Superfamily (MFS) drug:H+ antiporter CaMdr1, from Candida albicans, is responsible for the efflux of structurally diverse antifungals. MFS members share a common fold of 12−14 transmembrane helices (TMHs) forming two N- and C-domains. Each domain is arranged in a pseudo-symmetric fold of two tandems of 3-TMHs that alternatively expose the drug-binding site towards the inside or the outside of the yeast to promote drug binding and release.

How fungal multidrug transporters mediate hyper resistance through DNA amplification and mutation.

A significant portion of clinically observed antifungal resistance is mediated by ATP-binding cassette (ABC) and major facilitator superfamily (MFS) transport pumps that reside in the plasma membrane. We review the mechanisms responsible for this phenomenon. Hyper resistance is often brought about by several kinds of DNA amplification or by gain-of-function mutations in a variety of transcription factors.

Identifying the Novel Inhibitors Against the Mycolic Acid Biosynthesis Pathway Target "mtFabH" of .

Mycolic acids are the key constituents of mycobacterial cell wall, which protect the bacteria from antibiotic susceptibility, helping to subvert and escape from the host immune system. Thus, the enzymes involved in regulating and biosynthesis of mycolic acids can be explored as potential drug targets to kill (Mtb). Herein, Kyoto Encyclopedia of Genes and Genomes is used to understand the fatty acid metabolism signaling pathway and integrative computational approach to identify the novel lead molecules against the mtFabH (β-ketoacyl-acyl carrier protein synthase III), the key regulatory enzyme of the mycolic acid pathway.

New mixed ligand oxidovanadium(IV) complexes: Solution behavior, protein interaction and cytotoxicity.

Herein we report the synthesis of five new mononuclear mixed ligand oxidovanadium(IV) complexes [VO(L)(L)] (1-5) with tridentate O,N,O-donor aroylhydrazones as main ligand (HL) and N,N-chelating 2,2'-bipyridine (bipy) and 1,10-phenanthroline (phen) as co-ligand (L). The complexes were characterized by elemental and thermogravimetric analysis (TGA), IR, UV-vis, and electron paramagnetic resonance (EPR) spectroscopy, electrospray ionization-mass spectrometry (ESI-MS) and cyclic voltammetry (CV). The structure of 1-5 was confirmed by single crystal X-ray analysis and also optimized by density functional theory (DFT) methods.

Evaluation of DNA/BSA interaction and in vitro cell cytotoxicity of μ-oxido bridged divanadium(V) complexes containing ONO donor ligands.

Two new μ-oxido bridged divanadium (V) complexes, [VO(L)] (1 and 2) have been synthesized using bi-negative tridentate ONO-donor ligands, HL (HL = 4-tert-butyl-2-[[[3,5-di-tert-butyl-2-hydroxyphenyl]methylene]amino]phenol and HL = 5-bromo-2-[[[4-(diethylamino)-2-hydroxyphenyl]methylene]amino]phenol). The synthesized ligands and complexes have been characterized through FT-IR, UV-vis, NMR, and HR-ESI-MS techniques. Single crystal X-ray crystallography data confirmed distorted square pyramidal geometry for both the complexes.

A Chemogenomic Toolkit to Evaluate the "Ins and Outs" of Yeast Plasma Membrane Transporters.

Over the years, there has been a lot of emphasis on the development of high-throughput platforms that help identify transporters of drugs and xenobiotics. However, major hinderances in these approaches include substrate promiscuity and functional redundancy of membrane transporters. To tackle such issues, Almeida and colleagues (L.

Fluconazole resistant clinical isolates have increased levels of cell wall chitin and increased susceptibility to a glucosamine-6-phosphate synthase inhibitor.

In 2009 was first isolated as fungal pathogen of human disease from ear canal of a patient in Japan. In less than a decade, this pathogen has rapidly spread around the world and has now become a major health challenge that is of particular concern because many strains are resistant to multiple class of antifungal drugs. The lack of available antifungals and rapid increase of this fungal pathogen provides an incentive for the development of new and more potent anticandidal drugs and drug combinatorial treatments.