Fungal infections by drug-resistant Candida albicans pose a global public health threat. However, the pathogen's diploid genome greatly hinders genome-wide investigations of resistance mechanisms. ...Here, we develop an efficient piggyBac transposon-mediated mutagenesis system using stable haploid C. albicans to conduct genome-wide genetic screens. We find that null mutants in either gene FEN1 or FEN12 (encoding enzymes for the synthesis of very-long-chain fatty acids as precursors of sphingolipids) exhibit resistance to fluconazole, a first-line antifungal drug. Mass-spectrometry analyses demonstrate changes in cellular sphingolipid composition in both mutants, including substantially increased levels of several mannosylinositolphosphoceramides with shorter fatty-acid chains. Treatment with fluconazole induces similar changes in wild-type cells, suggesting a natural response mechanism. Furthermore, the resistance relies on a robust upregulation of sphingolipid biosynthesis genes. Our results shed light into the mechanisms underlying azole resistance, and the new transposon-mediated mutagenesis system should facilitate future genome-wide studies of C. albicans.
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► A novel Fe3O4-RGO–MnO2 nanocomposite is prepared for arsenic removal. ► The nanocomposite has a As (V) capacity of 12.22mgg−1 and As (III) of 14.04mgg−1. ► The nanocomposite has ...oxidation, adsorption and magnetic separation properties. ► Kinetic data were well described by the pseudo-second order model.
Graphite oxide (GO) synthesized from graphite powder was modified with Fe3O4 and MnO2 nanoparticles by a two-step co-precipitation reaction for removing As (III) and As (V) in water. The nanocomposites have a high adsorption capacity and excellent magnetic properties which enable the adsorbent to be separated by an external magnetic field. At pH 7.0, the monolayer adsorption amounts calculated by the Langmuir sorption model were 14.04mgg−1 and 12.22mgg−1 for As (III) and As (V), respectively. The high adsorption capacity was attributed to the large surface of GO which provides more adsorption sites by reducing the aggregation of Fe3O4 and MnO2 nanoparticles. In addition, the MnO2 on the adsorbent surface promoted the oxidation of As (III) to As (V) without addition of other oxidant and simultaneously participated in the adsorption of arsenic with Fe3O4. Furthermore, arsenic adsorption remained stable in a wide pH range 2–10, which is a limitation in most adsorbents. The experimental results suggest that this adsorbent is promising for treating arsenic contaminated natural water
Inorganic-framework molecularly imprinted TiO2/WO3 nanocomposites with molecular recognitive photocatalytic activity were first prepared successfully by a facile one-step sol-gel method using ...2-nitrophenol and 4-nitrophenol as template molecules, and tetrabutyl orthotitanate as titanium source as well as the precursor of functional monomer which could complex with template molecules. The template molecules could be completely removed by means of high-temperature calcination, avoiding the traditional extraction procedures that are time- as well as solvent-consuming. Compared to nonimprinted TiO2/WO3, the molecularly imprinted TiO2/WO3 shows a much higher adsorption capacity and selectivity toward the template molecules. The enhancement in terms of adsorption capacity and selectivity can be attributed to the chemical interaction between target molecules and imprinted cavities, as well as size matching between imprinted cavities and target molecules. The photocatalytic activity of molecularly imprinted TiO2/WO3 toward the target molecules is more than two times that of non-imprinted TiO2/WO3, a result of selective adsorption of target molecules on molecularly imprinted TiO2/WO3. The formation pathway of intermediate products in 2-nitrophenol and 4-nitrophenol degradation process was provided. Moreover, molecularly imprinted TiO2/WO3 exhibits high stability. The results indicate that inorganic-framework molecularly imprinted TiO2/WO3 nanocomposites have a promising prospect in the treatment of wastewater for irrigation.
► Catalytic ion was first applied to the bioleaching process of spent lithium-ion batteries. ► The bioleaching efficiency was great improved from 43.1% to 99.9% in the presence of copper ion. ► A new ...reaction model was proposed to explain the catalytic mechanism.
A copper-catalyzed bioleaching process was developed to recycle cobalt from spent lithium-ion batteries (mainly LiCoO
2) in this paper. The influence of copper ions on bioleaching of LiCoO
2 by
Acidithiobacillus ferrooxidans (
A.f) was investigated. It was shown that almost all cobalt (99.9%) went into solution after being bioleached for 6 days in the presence of 0.75
g/L copper ions, while only 43.1% of cobalt dissolution was obtained after 10 days without copper ions. EDX, XRD and SEM analyses additionally confirmed that the cobalt dissolution from spent lithium-ion batteries could be improved in the presence of copper ions. The catalytic mechanism was investigated to explain the enhancement of cobalt dissolution by copper ions, in which LiCoO
2 underwent a cationic interchange reaction with copper ions to form CuCo
2O
4 on the surface of the sample, which could be easily dissolved by Fe
3+.
Candida albicans, the most prevalent human fungal pathogen, is considered to be an obligate diploid that carries recessive lethal mutations throughout the genome. Here we demonstrate that C. albicans ...has a viable haploid state that can be derived from diploid cells under in vitro and in vivo conditions, and that seems to arise through a concerted chromosome loss mechanism. Haploids undergo morphogenetic changes like those of diploids, including the yeast-hyphal transition, chlamydospore formation and a white-opaque switch that facilitates mating. Haploid opaque cells of opposite mating type mate efficiently to regenerate the diploid form, restoring heterozygosity and fitness. Homozygous diploids arise spontaneously by auto-diploidization, and both haploids and auto-diploids show a similar reduction in fitness, in vitro and in vivo, relative to heterozygous diploids, indicating that homozygous cell types are transient in mixed populations. Finally, we constructed stable haploid strains with multiple auxotrophies that will facilitate molecular and genetic analyses of this important pathogen.
•Silver ions was first applied to the bioleaching process of spent lithium-ion batteries.•The bioleaching efficiency was great improved in the presence of silver ions.•A new reaction model was ...proposed to explain the catalytic mechanism.
The influence of silver ions (Ag+) on the bioleaching of cobalt from spent lithium batteries using Acidithiobacillus ferrooxidans (A. ferrooxidans) bacteria was investigated. The best effect was observed at Ag+ concentration of 0.02g/L, and the amount of leached cobalt was 98.4% in a period of 7days, whereas in the absence of Ag+, the amount of leached cobalt was only 43.1%. Based on the results of SEM, XRD and EDX investigation, it is deduced that Ag+ first reacted with cobalt to form AgCoO2 as an intermediate. A mechanism that is based on catalytic interactions is proposed to explain the enhanced leaching of Co using A. ferrooxidans.
Candida albicans is an opportunistic fungal pathogen of humans. It causes a variety of infections ranging from superficial mucocutaneous conditions to severe systemic diseases that result in ...substantial morbidity and mortality. This pathogen frequently forms biofilms resistant to antifungal drugs and the host immune system, leading to treatment failures. Recent research has demonstrated the potential of nanorobots to penetrate biological barriers and disrupt fungal biofilms. In this perspective paper, we provide a brief overview of recent breakthroughs in nanorobots for candidiasis treatment and discuss current challenges and prospects.
RGO@hematite nanohybrids were fabricated by in situ growth method under mild wet-chemical conditions. A series of characterization results indicate that the as-prepared hematite nanoparticles with ...relatively uniform sizes are embedded in RGO layers to form unique core–shell nanostructures. As an absorbing material, the RGO@hematite/polyvinylidene fluoride (PVDF) composites were prepared at various loadings of RGO@hematite (0–15wt%), and they exhibited strong microwave absorption in the microwave range of 2.0–18.0GHz. For example, RGO@hematite/PVDF composite with 5wt% loading has a strong absorbing peak at 5.76GHz and achieves a maximum absorbing value of −43.97dB. The absorbing peak position moves to lower frequencies with the increase of RGO@hematite loading. The mechanism for the enhanced wave absorbing properties was explained in detail.
In the original version of this Article, Haoping Liu, who conceptualized, designed and supervised the project and acquired funding, was inadvertently omitted from the author list. Furthermore, the ...affiliation of Jiaxin Gao and Haoping Liu with 'Department of Biological Chemistry, University of California, Irvine, CA 92697, USA' was omitted. Finally, funding from NIH grant GM117111, and contributions from Dr. Li-lin Du of NIBS for providing pPBura4 and pDUAL-PBase and Allan Bradley of Sanger for hyPBase, were not acknowledged. These errors have now been corrected in both the PDF and HTML versions of the Article.
In the human fungal pathogen Candida albicans, invasive hyphal growth is a well-recognized virulence trait. We employed transposon-mediated genome-wide mutagenesis, revealing that inactivating CTM1 ...blocks hyphal growth. CTM1 encodes a lysine (K) methyltransferase, which trimethylates cytochrome c (Cyc1) at K79. Mutants lacking CTM1 or expressing cyc1K79A grow as yeast under hyphae-inducing conditions, indicating that unmethylated Cyc1 suppresses hyphal growth. Transcriptomic analyses detected increased levels of the hyphal repressor NRG1 and decreased levels of hyphae-specific genes in ctm1Δ/Δ and cyc1K79A mutants, suggesting cyclic AMP (cAMP)-protein kinase A (PKA) signaling suppression. Co-immunoprecipitation and in vitro kinase assays demonstrated that unmethylated Cyc1 inhibits PKA kinase activity. Surprisingly, hyphae-defective ctm1Δ/Δ and cyc1K79A mutants remain virulent in mice due to accelerated proliferation. Our results unveil a critical role for cytochrome c in maintaining the virulence of C. albicans by orchestrating proliferation, growth mode, and metabolism. Importantly, this study identifies a biological function for lysine methylation on cytochrome c.
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•The methyltransferase Ctm1 is essential for the hyphal growth of Candida albicans•Ctm1 specifically catalyzes the trimethylation of cytochrome c (Cyc1) at lysine 79•Unmethylated Cyc1 binds to the catalytic subunits of PKA and inhibits their kinase activity•ctm1Δ/Δ mutant retains virulence in mice by improving proliferation via metabolic adaptation
Through a transposon-mediated genetic screen, Zeng et al. identify the methyltransferase Ctm1 as a critical regulator of hyphal growth. Ctm1 specifically methylates cytochrome c (Cyc1) at lysine 79. Unmethylated Cyc1 binds to the catalytic subunits of protein kinase A and inhibits their activity, blocking cAMP-PKA signaling and hyphal development.
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