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1.
Adv Mater ; : e2401349, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38657644

ABSTRACT

Phonon polaritons, the hybrid quasiparticles resulting from the coupling of photons and lattice vibrations, have gained significant attention in the field of layered van der Waals heterostructures. Particular interest has been paid to hetero-bicrystals composed of molybdenum oxide (MoO3) and hexagonal boron nitride (hBN), which feature polariton dispersion tailorable via avoided polariton mode crossings. In this work, we systematically study the polariton eigenmodes in MoO3-hBN hetero-bicrystals self-assembled on ultrasmooth gold using synchrotron infrared nanospectroscopy. We experimentally demonstrate that the spectral gap in bicrystal dispersion and corresponding regimes of negative refraction can be tuned by material layer thickness, and we quantitatively match these results with a simple analytic model. We also investigate polaritonic cavity modes and polariton propagation along "forbidden" directions in our microscale bicrystals, which arise from the finite in-plane dimension of the synthesized MoO3 micro-ribbons. Our findings shed light on the unique dispersion properties of polaritons in van der Waals heterostructures and pave the way for applications leveraging deeply sub-wavelength mid-infrared light matter interactions. This article is protected by copyright. All rights reserved.

2.
ACS Nano ; 17(22): 23057-23064, 2023 Nov 28.
Article in English | MEDLINE | ID: mdl-37948673

ABSTRACT

Low-dimensional, strongly anisotropic nanomaterials can support hyperbolic phonon polaritons, which feature strong light-matter interactions that can enhance their capabilities in sensing and metrology tasks. In this work, we report hyperbolic polaritonic rulers, based on microscale α-phase molybdenum trioxide (α-MoO3) waveguides and resonators suspended over an ultraflat gold substrate, which exhibit near-field polaritonic characteristics that are exceptionally sensitive to device geometry. Using scanning near-field optical microscopy, we show that these systems support strongly confined image polariton modes that exhibit ideal antisymmetric gap polariton dispersion, which is highly sensitive to air gap dimensions and can be described and predicted using a simple analytic model. Dielectric constants used for modeling are accurately extracted using near-field optical measurements of α-MoO3 waveguides in contact with the gold substrate. We also find that for nanoscale resonators supporting in-plane Fabry-Perot modes, the mode order strongly depends on the air gap dimension in a manner that enables a simple readout of the gap dimension with nanometer precision.

3.
Nano Lett ; 23(17): 7968-7974, 2023 Sep 13.
Article in English | MEDLINE | ID: mdl-37656036

ABSTRACT

Magnesium diboride (MgB2) has been explored as an alternative fuel to boron (B) due to its high energy density and the additive effect of magnesium (Mg) to promote B combustion. However, the primary oxidation of MgB2 does not occur unless it decomposes at a high temperature (830 °C), which makes ignition difficult and the reaction slow. Recently, two-dimensional (2D) exfoliated MgB2 nanosheets have attracted increasing attention due to their unique properties and potential applications in various fields. In this study, we investigate the potential of 2D exfoliated MgB2 nanosheets as solid fuels for overcoming the challenges of MgB2 combustion. We analyzed their oxidation behavior and energetic performance through material characterization and combustion tests under slow- and fast-heating conditions and compared their performance with those of bulk MgB2, B nanoparticles, and a B/Mg nanoparticle mixture. This study highlights the potential of MgB2 nanosheets as promising solid fuels with superior energetic properties.

4.
Med Mycol ; 61(2)2023 Feb 03.
Article in English | MEDLINE | ID: mdl-36715154

ABSTRACT

Candida glabrata is an opportunistic fungal pathogen and the second most prevalent species isolated from candidiasis patients. C. glabrata has intrinsic tolerance to antifungal drugs and oxidative stresses and the ability to adhere to mucocutaneous surfaces. However, knowledge about the regulation of its virulence traits is limited. The Spt-Ada-Gcn5 acetyltransferase (SAGA) complex modulates gene transcription by histone acetylation through the histone acetyltransferase (HAT) module comprised of Gcn5-Ada2-Ada3. Previously, we showed that the ada2 mutant was hypervirulent but displayed decreased tolerance to antifungal drugs and cell wall perturbing agents. In this study, we further characterized the functions of Ada3 and Gcn5 in C. glabrata. We found that single, double, or triple deletions of the HAT module, as expected, resulted in a decreased level of acetylation on histone H3 lysine 9 (H3K9) and defective growth. These mutants were more susceptible to antifungal drugs, oxidative stresses, and cell wall perturbing agents compared with the wild-type. In addition, HAT module mutants exhibited enhanced agar invasion and upregulation of adhesin and proteases encoding genes, whereas the biofilm formation of those mutants was impaired. Interestingly, HAT module mutants exhibited enhanced induction of catalases (CTA1) expression upon treatment with H2O2 compared with the wild-type. Lastly, although ada3 and gcn5 exhibited marginal hypervirulence, the HAT double and triple mutants were hypervirulent in a murine model of candidiasis. In conclusion, the HAT module of the SAGA complex plays unique roles in H3K9 acetylation, drug tolerance, oxidative stress response, adherence, and virulence in C. glabrata.


The present study characterizes the functions of the conserved histone acetyltransferase module in the pathogenesis of the pathogenic yeast Candida glabrata. The results indicated that this module has divergent roles in the pathogenesis of C. glabrata.


Subject(s)
Candidiasis , Saccharomyces cerevisiae Proteins , Animals , Mice , Histone Acetyltransferases/genetics , Histone Acetyltransferases/metabolism , Candida glabrata/genetics , Transcription Factors/genetics , Antifungal Agents , Hydrogen Peroxide , Candidiasis/veterinary , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae Proteins/metabolism
6.
Nano Lett ; 22(14): 5832-5840, 2022 07 27.
Article in English | MEDLINE | ID: mdl-35849552

ABSTRACT

We introduce and experimentally demonstrate electrically driven, spectrally selective thermal emitters based on globally aligned carbon nanotube metamaterials. The self-assembled metamaterial supports a high degree of nanotube ordering, enabling nanoscale ribbons patterned in the metamaterial to function both as Joule-heated incandescent filaments and as infrared hyperbolic resonators imparting spectral selectivity to the thermal radiation. Devices batch-fabricated on a single chip emit polarized thermal radiation with peak wavelengths dictated by their hyperbolic resonances, and their nanoscale heated dimensions yield modulation rates as high as 1 MHz. As a proof of concept, we show that two sets of thermal emitters on the same chip, operating with different peak wavelengths and modulation rates, can be used to sense carbon dioxide with one detector. We anticipate that the combination of batch fabrication, modulation bandwidth, and spectral tuning with chip-based nanotube thermal emitters will enable new modalities in multiplexed infrared sources.


Subject(s)
Nanotubes, Carbon , Electricity , Hot Temperature
7.
Proc Natl Acad Sci U S A ; 119(12): e2122085119, 2022 03 22.
Article in English | MEDLINE | ID: mdl-35294279

ABSTRACT

Control over symmetry breaking in three-dimensional electromagnetic systems offers a pathway to tailoring their optical activity. We introduce fractured Pancharatnam­Berry-phase metasurface systems, in which a full-waveplate geometric phase metasurface is fractured into two half-waveplate-based metasurfaces and actively configured using shear displacement. Local relative rotations between stacked half-nanowaveplates within the metasurface system are transduced by shear displacement, leading to dynamic modulation of their collective geometric phase properties. We apply this concept to pairs of periodic Pancharatnam­Berry-phase metasurfaces and experimentally show that these systems support arbitrary and reconfigurable broadband circular birefringence response. High-speed circular birefringence modulation is demonstrated with modest shearing speeds, indicating the potential for these concepts to dynamically control polarization states with fast temporal responses. We anticipate that fractured geometric phase metasurface systems will serve as a nanophotonic platform that leverages systems-level symmetry breaking to enable active electromagnetic wave control.

8.
ACS Nano ; 16(2): 3027-3035, 2022 Feb 22.
Article in English | MEDLINE | ID: mdl-35041379

ABSTRACT

van der Waals nanomaterials supporting phonon polariton quasiparticles possess extraordinary light confinement capabilities, making them ideal systems for molecular sensing, thermal emission, and subwavelength imaging applications, but they require defect-free crystallinity and nanostructured form factors to fully showcase these capabilities. We introduce bottom-up-synthesized α-MoO3 structures as nanoscale phonon polaritonic systems that feature tailorable morphologies and crystal qualities consistent with bulk single crystals. α-MoO3 nanoribbons serve as low-loss hyperbolic Fabry-Pérot nanoresonators, and we experimentally map hyperbolic resonances over four Reststrahlen bands spanning the far- and mid-infrared spectral range, including resonance modes beyond the 10th order. The measured quality factors are the highest from phonon polaritonic van der Waals structures to date. We anticipate that bottom-up-synthesized polaritonic van der Waals nanostructures will serve as an enabling high-performance and low-loss platform for infrared optical and optoelectronic applications.

9.
Angew Chem Int Ed Engl ; 61(24): e202112400, 2022 Jun 13.
Article in English | MEDLINE | ID: mdl-34936187

ABSTRACT

Inorganic chiral hybrid nanostructures that embed chirality within distinct material compositions can create novel chiral properties and functionalities absent from achiral nanostructures; however, they remain largely unexplored. We report, for the first time, a class of chiral plasmonic metal-semiconductor core-shell nanostructures that employ structurally chiral nanoparticles as chirality inducing templates to grow functional shell materials, which allowed us to independently control material parameters such as core geometry and shell thickness, as well as handedness of the system. We experimentally and theoretically achieved enhanced and tunable chiroptical activity of the heterostructures as a result of the core-shell strong coupling effect. As a proof-of-concept demonstration, we demonstrate that the chiral hybrid nanostructures can drive chirality-dependent photocatalytic hydrogen generation under circularly polarized light. This study enables rational design and functionalization of chiral hybrid nanomaterials towards enhanced chiral light-matter interactions and chiral device applications.

10.
Front Pharmacol ; 12: 746496, 2021.
Article in English | MEDLINE | ID: mdl-34899300

ABSTRACT

Tuberculosis (TB) is a leading cause of death from a single infectious agent, Mycobacterium tuberculosis (Mtb). Although progress has been made in TB control, still about 10 million people worldwide develop TB annually and 1.5 million die of the disease. The rapid emergence of aggressive, drug-resistant strains and latent infections have caused TB to remain a global health challenge. TB treatments are lengthy and their side effects lead to poor patient compliance, which in turn has contributed to the drug resistance and exacerbated the TB epidemic. The relatively low output of newly approved antibiotics has spurred research interest toward alternative antibacterial molecules such as silver nanoparticles (AgNPs). In the present study, we use the natural biopolymer alginate to serve as a stabilizer and/or reductant to green synthesize AgNPs, which improves their biocompatibility and avoids the use of toxic chemicals. The average size of the alginate-capped AgNPs (ALG-AgNPs) was characterized as nanoscale, and the particles were round in shape. Drug susceptibility tests showed that these ALG-AgNPs are effective against both drug-resistant Mtb strains and dormant Mtb. A bacterial cell-wall permeability assay showed that the anti-mycobacterial action of ALG-AgNPs is mediated through an increase in cell-wall permeability. Notably, the anti-mycobacterial potential of ALG-AgNPs was effective in both zebrafish and mouse TB animal models in vivo. These results suggest that ALG-AgNPs could provide a new therapeutic option to overcome the difficulties of current TB treatments.

11.
Nat Commun ; 11(1): 1521, 2020 03 23.
Article in English | MEDLINE | ID: mdl-32251295

ABSTRACT

Cryptococcus neoformans causes fatal fungal meningoencephalitis. Here, we study the roles played by fungal kinases and transcription factors (TFs) in blood-brain barrier (BBB) crossing and brain infection in mice. We use a brain infectivity assay to screen signature-tagged mutagenesis (STM)-based libraries of mutants defective in kinases and TFs, generated in the C. neoformans H99 strain. We also monitor in vivo transcription profiles of kinases and TFs during host infection using NanoString technology. These analyses identify signalling components involved in BBB adhesion and crossing, or survival in the brain parenchyma. The TFs Pdr802, Hob1, and Sre1 are required for infection under all the conditions tested here. Hob1 controls the expression of several factors involved in brain infection, including inositol transporters, a metalloprotease, PDR802, and SRE1. However, Hob1 is dispensable for most cellular functions in Cryptococcus deuterogattii R265, a strain that does not target the brain during infection. Our results indicate that Hob1 is a master regulator of brain infectivity in C. neoformans.


Subject(s)
Blood-Brain Barrier/metabolism , Cryptococcus neoformans/pathogenicity , Homeodomain Proteins/metabolism , Meningitis, Cryptococcal/pathology , Meningoencephalitis/pathology , Transcription Factors/metabolism , Animals , Brain/microbiology , Brain/pathology , Cryptococcus gattii/genetics , Cryptococcus gattii/metabolism , Cryptococcus gattii/pathogenicity , Cryptococcus neoformans/genetics , Cryptococcus neoformans/metabolism , Disease Models, Animal , Female , Fungal Proteins , Gene Expression Profiling , Gene Expression Regulation, Fungal , Homeodomain Proteins/genetics , Humans , Meningitis, Cryptococcal/microbiology , Meningoencephalitis/microbiology , Mice , Mutagenesis , Mutation , Permeability , Phosphotransferases/genetics , Signal Transduction/genetics , Transcription Factors/genetics
12.
Nano Lett ; 19(5): 3131-3137, 2019 05 08.
Article in English | MEDLINE | ID: mdl-30950280

ABSTRACT

We show that packed, horizontally aligned films of single-walled carbon nanotubes are hyperbolic metamaterials with ultrasubwavelength unit cells and dynamic tunability. Using Mueller matrix ellipsometry, we characterize the films' optical properties, which are doping level dependent, and find a broadband hyperbolic region tunable in the mid-infrared. To characterize the dispersion of in-plane hyperbolic plasmon modes, we etch the nanotube films into nanoribbons with differing widths and orientations relative to the nanotube axis, and we observe that the hyperbolic modes support strong light localization. An agreement between the experiments and theoretical models using the ellipsometry data indicates that the packed carbon nanotubes support bulk anisotropic responses at the nanoscale. Self-assembled films of carbon nanotubes are well-suited for applications in thermal emission and photodetection, and they serve as model systems for studying light-matter interactions in the deep subwavelength regime.

13.
Nano Lett ; 18(2): 1124-1129, 2018 02 14.
Article in English | MEDLINE | ID: mdl-29314852

ABSTRACT

Understanding and controlling the phononic characteristics in solids is crucial to elucidate many physical phenomena and develop new phononic devices with optimal performance. Although substantial progress on the spatial control of phonons by material design has been achieved, the manipulation of phonons in the time domain has been less studied but can elucidate in-depth insight into various phonon-coupling processes. In this work, we explore different time-domain pump-control(s)-probe phonon manipulation schemes in both simulations and experiments with good consistency. In particular, we use an Au-Ag core-shell nanoparticle with a manifestation of multiple phonon vibrational modes as a model system for multimodal-phonon manipulation, and we demonstrate that the simple addition of a femtosecond optical control pulse to an all-optical pump-probe phonon measurement can enhance or suppress the fundamental breathing phonon mode of nanoparticles depending on the time separation between the pump and the control pulses. A more advanced control of the higher-order phonon modes and their interplay has also been achieved using two sequential and independently tunable optical control pulses, which enables the discriminatory modal manipulation of phonons for the first time. This work represents a significant step toward a deep understanding of the phonon-mediated physical and chemical processes and a development of new nanoscale materials with desirable functionalities and properties.

14.
Article in English | MEDLINE | ID: mdl-29311082

ABSTRACT

Candida glabrata, the second most frequent cause of candidiasis after Candida albicans, is an emerging human fungal pathogen that is intrinsically drug tolerant. Currently, studies of C. glabrata genes involved in drug tolerance are limited. Ada2, a component serving as a transcription adaptor of the Spt-Ada-Gcn5 acetyltransferase (SAGA) complex, is required for antifungal drug tolerance and virulence in C. albicans However, its roles in C. glabrata remain elusive. In this study, we found that ada2 mutants demonstrated severe growth defects at 40°C but only mild defects at 37°C or 25°C. In addition, C. glabrata ada2 mutants exhibited pleiotropic phenotypes, including susceptibility to three classes of antifungal drugs (i.e., azoles, echinocandins, and polyenes) and cell wall-perturbing agents but resistance to the endoplasmic reticulum stressor tunicamycin. According to RNA sequence analysis, the expression of 43 genes was downregulated and the expression of 442 genes was upregulated in the ada2 mutant compared to their expression in the wild type. C. glabrata ADA2, along with its downstream target ERG6, controls antifungal drug tolerance and cell wall integrity. Surprisingly, ada2 mutants were hypervirulent in a murine model of systemic infection, possibly due to the upregulation of multiple adhesin-like genes, increased agar invasion, and overstimulation of murine tumor necrosis factor alpha production.


Subject(s)
Antifungal Agents/therapeutic use , Candida glabrata/pathogenicity , Candidiasis/drug therapy , Candidiasis/metabolism , Fungal Proteins/metabolism , Animals , Candidiasis/genetics , Cell Wall/drug effects , Cell Wall/metabolism , Drug Resistance, Fungal/genetics , Fungal Proteins/genetics , Male , Mice , Mice, Inbred ICR , Virulence/genetics
15.
Virulence ; 9(1): 331-347, 2018 01 01.
Article in English | MEDLINE | ID: mdl-29254431

ABSTRACT

Candida tropicalis is one of the most important human fungal pathogens causing superficial infections in locations such as the oral mucosa and genital tract, as well as systemic infections with high mortality. In its sister species Candida albicans, the cyclic AMP/protein kinase A (cAMP/PKA) pathway regulates fungal adhesion and dimorphism, both of which correlate closely with virulence. CaTpk1 and CaTpk2, the catalytic subunits of PKA, not only share redundant functions in hyphal growth, adhesion, and biofilm formation, but also have distinct roles in stress responses and pathogenesis, respectively. However, studies on PKA in the emerging fungal pathogen C. tropicalis are limited. Our results suggest that Tpk1 is involved in cell wall integrity and drug tolerance. The tpk2/tpk2 mutants, which have no protein kinase A activity, have reduced hyphal growth and adhesion. In addition, the tpk1/tpk1 tpk2/tpk2 double deletion mutant demonstrated delayed growth and impaired hyphal formation. In a murine model of systemic infection, both TPK1 and TPK2 were required for full virulence. We further found that EFG1 and HWP1 expression is regulated by PKA, while BCR1, FLO8, GAL4, and RIM101 are upregulated in the tpk1/tpk1 tpk2/tpk2 mutant. This study demonstrates that Tpk1 is involved in drug tolerance and cell wall integrity, while Tpk2 serves as a key regulator in dimorphism and adhesion. Both Tpk1 and Tpk2 are required for growth and full virulence in C. tropicalis.


Subject(s)
Candida tropicalis/enzymology , Candida tropicalis/growth & development , Cyclic AMP-Dependent Protein Kinases/metabolism , Virulence Factors/metabolism , Animals , Antifungal Agents/metabolism , Candida tropicalis/drug effects , Candida tropicalis/pathogenicity , Candidiasis/microbiology , Candidiasis/pathology , Cell Adhesion , Cell Wall/metabolism , Cells, Cultured , Cyclic AMP-Dependent Protein Kinases/genetics , Disease Models, Animal , Drug Tolerance , Gene Deletion , Humans , Hyphae/growth & development , Mice , Virulence
16.
J Am Chem Soc ; 139(17): 6070-6073, 2017 05 03.
Article in English | MEDLINE | ID: mdl-28414901

ABSTRACT

Chiral organizations ubiquitously exist in biomaterials via hierarchical assembly of chiral molecules, but assembly of chiral inorganic nanocrystals (NCs) has been lacking. Recent development of cinnabar HgS NCs that can possess precisely engineered chirality originating from both atomic lattice and morphology offers an emerging class of inorganic building blocks to explore their hierarchical assembly. Two different forms of suprastructures, collinear chains and propellers, have been achieved with various chiral HgS NC building blocks via distinct assembly mechanisms. The chiroptical responses of suprastructures are further evaluated both experimentally and theoretically, and are found to uniquely depend on intrinsic chirality of building blocks and their coupling. Our study therefore opens up a gateway to new assembled inorganic suprastructures with desired chiroptical response for wide-ranging functionalities and applications by bottom-up modular approach.

17.
Nat Commun ; 8: 14312, 2017 02 02.
Article in English | MEDLINE | ID: mdl-28148957

ABSTRACT

Cooperative chirality phenomena extensively exist in biomolecular and organic systems via intra- and inter-molecular interactions, but study of inorganic materials has been lacking. Here we report, experimentally and theoretically, cooperative chirality in colloidal cinnabar mercury sulfide nanocrystals that originates from chirality interplay between the crystallographic lattice and geometric morphology at different length scales. A two-step synthetic scheme is developed to allow control of critical parameters of these two types of handedness, resulting in different chiral interplays expressed as observables through materials engineering. Furthermore, we adopt an electromagnetic model with the finite element method to elucidate cooperative chirality in inorganic systems, showing excellent agreement with experimental results. Our study enables an emerging class of nanostructures with tailored cooperative chirality that is vital for fundamental understanding of nanoscale chirality as well as technology applications based on new chiroptical building blocks.

18.
Virulence ; 8(2): 222-236, 2017 02 17.
Article in English | MEDLINE | ID: mdl-27820668

ABSTRACT

Invasive fungal infections remain a major cause of morbidity and mortality in immunocompromised patients, and such infections are a substantial burden to healthcare systems around the world. However, the clinically available armamentarium for invasive fungal diseases is limited to 3 main classes (i.e., polyenes, triazoles, and echinocandins), and each has defined limitations related to spectrum of activity, development of resistance, and toxicity. Further, current antifungal therapies are hampered by limited clinical efficacy, high rates of toxicity, and significant variability in pharmacokinetic properties. New antifungal agents, new formulations, and novel combination regimens may improve the care of patients in the future by providing improved strategies to combat challenges associated with currently available antifungal agents. Likewise, therapeutic drug monitoring may be helpful, but its present use remains controversial due to the lack of available data. This article discusses new facets of antifungal therapy with a focus on new antifungal formulations and the synergistic effects between drugs used in combination therapy.


Subject(s)
Antifungal Agents/chemistry , Antifungal Agents/therapeutic use , Drug Discovery , Invasive Fungal Infections/drug therapy , Mycoses/drug therapy , Drug Synergism , Drug Therapy, Combination , Echinocandins/chemistry , Echinocandins/therapeutic use , Humans , Immunocompromised Host , Invasive Fungal Infections/microbiology , Mycoses/microbiology , Polyenes/chemistry , Polyenes/therapeutic use , Triazoles/chemistry , Triazoles/therapeutic use
19.
FEMS Yeast Res ; 15(4): fov016, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25878052

ABSTRACT

Human fungal infections have significantly increased in recent years due to the emergence of immunocompromised patients with AIDS and cancer. Among them, Candida species are frequently isolated and associated with high mortality if not appropriately treated. Current antifungal drugs (azoles, echinocandins and polyenes) are not sufficient to combat Candida species particularly those that are drug resistant. Calcineurin, a calcium/calmodulin-dependent protein phosphatase, is an attractive antifungal drug target, and its inhibitor (FK506 or cyclosporin A) can be combined with azoles or echinocandins for use against multidrug-resistant Candida species. The role of calcineurin in the hyphal growth of Candida albicans is controversial, but its roles in C. dubliniensis, C. tropicalis and C. lusitaniae can be demonstrated. In addition, calcineurin is required for virulence of Candida species in murine systemic, ocular or urinary infection models. However, the requirement for calcineurin substrate Crz1 in these infection models varies in Candida species, suggesting that Crz1 has diverse functions in different Candida species. Besides being critical for growth in serum of Candida species, calcineurin is critical for plasma membrane integrity and growth at body temperature (37°C) uniquely in C. glabrata, suggesting that Candida calcineurin controls pathogenesis via various novel mechanisms. In this review, we summarize studies of calcineurin signaling and hyphal growth, virulence and its relationship with drug tolerance in Candida species, focusing on the divergent and conserved functions.


Subject(s)
Calcineurin/metabolism , Candida/physiology , Candida/pathogenicity , Gene Expression Regulation, Fungal , Signal Transduction , Stress, Physiological , Animals , Candida/growth & development , Humans , Hyphae/growth & development , Mice , Virulence
20.
PLoS One ; 10(1): e0116974, 2015.
Article in English | MEDLINE | ID: mdl-25602740

ABSTRACT

ScOpi1p is a well-characterized transcriptional repressor and master regulator of inositol and phospholipid biosynthetic genes in the baker's yeast Saccharomyces cerevisiae. An ortholog has been shown to perform a similar function in the pathogenic fungus Candida glabrata, but with the distinction that CgOpi1p is essential for growth in this organism. However, in the more distantly related yeast Yarrowia lipolytica, the OPI1 homolog was not found to regulate inositol biosynthesis, but alkane oxidation. In Candida albicans, the most common cause of human candidiasis, its Opi1p homolog, CaOpi1p, has been shown to complement a S. cerevisiae opi1∆ mutant for inositol biosynthesis regulation when heterologously expressed, suggesting it might serve a similar role in this pathogen. This was tested in the pathogen directly in this report by disrupting the OPI1 homolog and examining its phenotypes. It was discovered that the OPI1 homolog does not regulate INO1 expression in C. albicans, but it does control SAP2 expression in response to bovine serum albumin containing media. Meanwhile, we found that CaOpi1 represses filamentous growth at lower temperatures (30 °C) on agar, but not in liquid media. Although, the mutant does not affect virulence in a mouse model of systemic infection, it does affect virulence in a rat model of vaginitis. This may be because Opi1p regulates expression of the SAP2 protease, which is required for rat vaginal infections.


Subject(s)
Candida albicans/metabolism , Candida albicans/pathogenicity , Fungal Proteins/metabolism , Animals , Aspartic Acid Endopeptidases/genetics , Aspartic Acid Endopeptidases/metabolism , Candida albicans/growth & development , Fungal Proteins/genetics , Gene Expression Regulation, Fungal , Inositol/metabolism , Mice , Virulence , Yarrowia/growth & development , Yarrowia/metabolism , Yarrowia/pathogenicity
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