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1.
Adv Mater ; : e2401349, 2024 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-38657644

RESUMO

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.
Artigo em Inglês | MEDLINE | ID: mdl-37948673

RESUMO

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.
Artigo em Inglês | MEDLINE | ID: mdl-37656036

RESUMO

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.
Plant Cell Rep ; 42(8): 1365-1378, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37269374

RESUMO

KEY MESSAGE: DcWRKY5 increases the antioxidant enzyme activity and proline accumulation, oppositely, reduces the accumulation of ROS and MDA, through directly activating the genes expression, finally enhances the salt and drought tolerance. Drought and salinity are two main environmental factors that limit the large-scale cultivation of the medicinal plant Dioscorea composita (D. composita). WRKY transcription factors (TFs) play vital roles in regulating drought and salt tolerance in plants. Nevertheless, the molecular mechanism of WRKY TF mediates drought and salt resistance of D. composita remains largely unknown. Here, we isolated and characterized a WRKY TF from D. composita, namely DcWRKY5, which was localized to the nucleus and bound to the W-box cis-acting elements. Expression pattern analysis showed that it was highly expressed in root and significantly up-regulated in the presence of salt, polyethylene glycol-6000 (PEG-6000) and abscisic acid (ABA). Heterologous expression of DcWRKY5 increased salt and drought tolerance in Arabidopsis, but was insensitive to ABA. In addition, compared with the wild type, the DcWRKY5 overexpressing transgenic lines had more proline, higher antioxidant enzyme (POD, SOD, and CAT) activities, less reactive oxygen species (ROS) and malondialdehyde (MDA). Correspondingly, the overexpression of DcWRKY5 modulated the expression of genes related to salt and drought stresses, such as AtSS1, AtP5CS1, AtCAT, AtSOD1, AtRD22, and AtABF2. Dual luciferase assay and Y1H were further confirmed that DcWRKY5 activate the promoter of AtSOD1 and AtABF2 through directly binding to the enrichment region of the W-box cis-acting elements. These results suggest that DcWRKY5 is a positive regulator of the drought and salt tolerance in D. composita and has potential applications in transgenic breeding.


Assuntos
Arabidopsis , Dioscorea , Dioscorea/genética , Dioscorea/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Secas , Tolerância ao Sal/genética , Antioxidantes/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estresse Fisiológico/genética , Melhoramento Vegetal , Ácido Abscísico/metabolismo , Arabidopsis/genética , Regulação da Expressão Gênica de Plantas
5.
Plant Physiol Biochem ; 196: 746-758, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36827956

RESUMO

Dioscorea composita (D. composita) is an important medicinal plant worldwide with high economic value. However, its large-scale cultivation was limited by soil salinization. Identification of genes and their mechanisms of action in response to salt stress are critically important. In the present study, we isolated a classical WRKY transcription factor from D. composita, namely DcWRKY12, and analyzed its function in salt tolerance. Expression pattern analysis showed DcWRKY12 is mainly expressed in roots and significantly induced by NaCl, polyethylene glycol-6000 (PEG-6000), and abscisic acid (ABA). Phenotypic and physiological analyses revealed that heterologous expression of DcWRKY12 enhanced salt and osmotic stress tolerance by increasing antioxidant enzyme activity, osmoregulatory substance content, maintaining relative water content and ion homeostasis, decreasing reactive oxygen species and malondialdehyde content. Correspondingly, the overexpression of DcWRKY12 modulated the expression of salt stress-responsive and ion transport-related genes. Dual luciferase assay and Y1H were further confirmed that DcWRKY12 activates the promoter of AtRCI2A through directly binding to the specific W-box cis-acting elements. These results suggest that DcWRKY12 is a positive regulator of salt tolerance in D. composita and has potential applications in salt stress.


Assuntos
Arabidopsis , Dioscorea , Arabidopsis/genética , Dioscorea/genética , Dioscorea/metabolismo , Tolerância ao Sal , Estresse Fisiológico/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Ácido Abscísico/metabolismo , Regulação da Expressão Gênica de Plantas , Plantas Geneticamente Modificadas/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
6.
Med Mycol ; 61(2)2023 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-36715154

RESUMO

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.


Assuntos
Candidíase , Proteínas de Saccharomyces cerevisiae , Animais , Camundongos , Histona Acetiltransferases/genética , Histona Acetiltransferases/metabolismo , Candida glabrata/genética , Fatores de Transcrição/genética , Antifúngicos , Peróxido de Hidrogênio , Candidíase/veterinária , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
8.
Nano Lett ; 22(14): 5832-5840, 2022 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-35849552

RESUMO

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.


Assuntos
Nanotubos de Carbono , Eletricidade , Temperatura Alta
9.
Proc Natl Acad Sci U S A ; 119(12): e2122085119, 2022 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-35294279

RESUMO

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.

10.
ACS Nano ; 16(2): 3027-3035, 2022 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-35041379

RESUMO

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.

11.
Angew Chem Int Ed Engl ; 61(24): e202112400, 2022 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-34936187

RESUMO

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.

12.
J Plant Physiol ; 269: 153592, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34923363

RESUMO

Dioscorea composita (D. composita) is a perennial dioecious herb with strong biotic and abiotic stress tolerance. However, what roles WRKY transcription factors might play in regulating abiotic stress responses in this medicinal plant is unknown. Here, we isolated DcWRKY3 from D. composita and analyzed its role in stress tolerance. DcWRKY3 is a group I WRKY transcription factor that localized to the nucleus and specifically bound to the W-box cis-elements, but lacked transcriptional activation activity in yeast cells. The expression of DcWRKY3 was strongly affected by salt stress. The heterologous expression of DcWRKY3 strongly enhanced the seed germination rate and root length of Arabidopsis thaliana under salt stress. The DcWRKY3-expressing transgenic lines (DcWRKY3-OEs) also showed higher proline content and antioxidant enzyme activity but lower malondialdehyde and reactive oxygen (ROS) levels compared with the wild type. Moreover, these plants showed upregulated expression of genes related to the salt-stress response and ROS clearance. These findings indicate that DcWRKY3 plays a positive role in the salt-stress response by improving the ROS scavenging ability and maintaining the balance of osmotic pressure in plants. Further studies showed that DcWRKY3 binds to the promoter of AtP5CS1, but not AtSOD and AtRD22, suggesting that DcWRKY3 improves salt tolerance in plants by directly or indirectly regulating the expression of downstream genes. This functional characterization of DcWRKY3 provides new insight into the molecular mechanism underlying the response of D. composita to salt stress.


Assuntos
Arabidopsis/genética , Arabidopsis/fisiologia , Dioscorea/genética , Proteínas de Plantas/genética , Plantas Geneticamente Modificadas/genética , Tolerância ao Sal/genética , Estresse Fisiológico/genética , Fatores de Transcrição/genética , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Fatores de Transcrição/metabolismo
13.
Front Pharmacol ; 12: 746496, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34899300

RESUMO

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.

14.
Nano Lett ; 21(20): 8595-8601, 2021 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-34644094

RESUMO

Polarization-sensitive optical coherence tomography (PS-OCT) reveals the subsurface microstructure of biological tissue and provides information regarding the polarization state of light backscattered from tissue. Complementing OCT's structural signal with molecular imaging requires strategies to simultaneously detect multiple exogenous contrast agents with high specificity in tissue. Specific detection of molecular probes enables the parallel visualization of physiological, cellular, and molecular processes. Here we demonstrate that, by combining PS-OCT and spectral contrast (SC)-OCT measurements, we can distinguish signatures of different gold nanobipyramids (GNBPs) in lymphatic vessels from the surrounding tissue and blood vessels in live mouse models. This technique could well be extended to other anisotropic nanoparticle-based OCT contrast agents and presents significant progress toward enabling OCT molecular imaging.


Assuntos
Nanopartículas , Tomografia de Coerência Óptica , Animais , Modelos Animais de Doenças , Ouro , Camundongos
15.
Nat Commun ; 11(1): 1521, 2020 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-32251295

RESUMO

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.


Assuntos
Barreira Hematoencefálica/metabolismo , Cryptococcus neoformans/patogenicidade , Proteínas de Homeodomínio/metabolismo , Meningite Criptocócica/patologia , Meningoencefalite/patologia , Fatores de Transcrição/metabolismo , Animais , Encéfalo/microbiologia , Encéfalo/patologia , Cryptococcus gattii/genética , Cryptococcus gattii/metabolismo , Cryptococcus gattii/patogenicidade , Cryptococcus neoformans/genética , Cryptococcus neoformans/metabolismo , Modelos Animais de Doenças , Feminino , Proteínas Fúngicas , Perfilação da Expressão Gênica , Regulação Fúngica da Expressão Gênica , Proteínas de Homeodomínio/genética , Humanos , Meningite Criptocócica/microbiologia , Meningoencefalite/microbiologia , Camundongos , Mutagênese , Mutação , Permeabilidade , Fosfotransferases/genética , Transdução de Sinais/genética , Fatores de Transcrição/genética
16.
Nano Lett ; 19(5): 3131-3137, 2019 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-30950280

RESUMO

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.

17.
Science ; 363(6427): 619-623, 2019 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-30733415

RESUMO

The human body absorbs and loses heat largely through infrared radiation centering around a wavelength of 10 micrometers. However, neither our skin nor the textiles that make up clothing are capable of dynamically controlling this optical channel for thermal management. By coating triacetate-cellulose bimorph fibers with a thin layer of carbon nanotubes, we effectively modulated the infrared radiation by more than 35% as the relative humidity of the underlying skin changed. Both experiments and modeling suggest that this dynamic infrared gating effect mainly arises from distance-dependent electromagnetic coupling between neighboring coated fibers in the textile yarns. This effect opens a pathway for developing wearable localized thermal management systems that are autonomous and self-powered, as well as expanding our ability to adapt to demanding environments.

18.
Nano Lett ; 18(2): 1124-1129, 2018 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-29314852

RESUMO

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.

19.
Artigo em Inglês | MEDLINE | ID: mdl-29311082

RESUMO

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.


Assuntos
Antifúngicos/uso terapêutico , Candida glabrata/patogenicidade , Candidíase/tratamento farmacológico , Candidíase/metabolismo , Proteínas Fúngicas/metabolismo , Animais , Candidíase/genética , Parede Celular/efeitos dos fármacos , Parede Celular/metabolismo , Farmacorresistência Fúngica/genética , Proteínas Fúngicas/genética , Masculino , Camundongos , Camundongos Endogâmicos ICR , Virulência/genética
20.
Virulence ; 9(1): 331-347, 2018 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-29254431

RESUMO

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.


Assuntos
Candida tropicalis/enzimologia , Candida tropicalis/crescimento & desenvolvimento , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Fatores de Virulência/metabolismo , Animais , Antifúngicos/metabolismo , Candida tropicalis/efeitos dos fármacos , Candida tropicalis/patogenicidade , Candidíase/microbiologia , Candidíase/patologia , Adesão Celular , Parede Celular/metabolismo , Células Cultivadas , Proteínas Quinases Dependentes de AMP Cíclico/genética , Modelos Animais de Doenças , Tolerância a Medicamentos , Deleção de Genes , Humanos , Hifas/crescimento & desenvolvimento , Camundongos , Virulência
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