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1.
Med Microbiol Immunol ; 213(1): 13, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-38967888

RESUMEN

Candida auris is an emerging pathogenic yeast that has been categorized as a global public health threat and a critical priority among fungal pathogens. Despite this, the immune response against C. auris infection is still not well understood. Hosts fight Candida infections through the immune system that recognizes pathogen-associated molecular patterns such as ß-glucan, mannan, and chitin on the fungal cell wall. In this study, levels of ß-glucan and mannan exposures in C. auris grown under different physiologically relevant stimuli were quantified by flow cytometry-based analysis. Lactate, hypoxia, and sublethal concentration of fluconazole trigger a decrease in surface ß-glucan while low pH triggers an increase in ß-glucan. There is no inverse pattern between exposure levels of ß-glucan and mannan in the cell wall architecture among the three clades. To determine the effect of cell wall remodeling on the immune response, a phagocytosis assay was performed, followed by quantification of released cytokines by ELISA. Lactate-induced decrease in ß-glucan leads to reduced uptake of C. auris by PMA-differentiated THP-1 and RAW 264.7 macrophages. Furthermore, reduced production of CCL3/MIP-1⍺ but not TNF-⍺ and IL-10 were observed. An in vivo infection analysis using silkworms reveals that a reduction in ß-glucan triggers an increase in the virulence of C. auris. This study demonstrates that ß-glucan alteration occurs in C. auris and serves as an escape mechanism from immune cells leading to increased virulence.


Asunto(s)
Candida auris , Pared Celular , Evasión Inmune , beta-Glucanos , beta-Glucanos/metabolismo , Animales , Virulencia , Ratones , Pared Celular/inmunología , Pared Celular/química , Pared Celular/metabolismo , Humanos , Candida auris/patogenicidad , Células RAW 264.7 , Candidiasis/microbiología , Candidiasis/inmunología , Citocinas/metabolismo , Fagocitosis , Macrófagos/inmunología , Macrófagos/microbiología , Mananos/farmacología , Ácido Láctico/metabolismo , Modelos Animales de Enfermedad , Células THP-1
2.
Int J Mol Sci ; 25(5)2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38473746

RESUMEN

Inflammatory bowel disease (IBD) is a chronic inflammatory condition of the digestive tract and is closely associated with the homeostasis of the gut microbiota. Inulin, as a natural prebiotic, displays anti-inflammatory activity and maintains equilibrium of the intestinal microbiota. In this study, our research aimed to explore the potential of inulin in enhancing intestinal immunity and reducing inflammation in stress-recurrent IBD. In this study, a co-culture intestinal epithelium model and a stress-recurrent IBD mouse model was used to examine the protective effects of inulin. It was observed that inulin digesta significantly reduced pro-inflammatory cytokine expression (CXCL8/IL8 and TNFA) and increased MUC2 expression in intestinal epithelial cells. In vivo, our findings showed that Inulin intake significantly prevented IBD symptoms. This was substantiated by a decrease in serum inflammatory markers (IL-6, CALP) and a downregulation of inflammatory cytokine (Il6) in colon samples. Additionally, inulin intake led to an increase in short-chain fatty acids (SCFAs) in cecal contents and a reduction in the expression of endoplasmic reticulum (ER) stress markers (CHOP, BiP). Our results highlight that inulin can improve stress-recurrent IBD symptoms by modulating microbiota composition, reducing inflammation, and alleviating ER stress. These findings suggested the therapeutic potential of inulin as a dietary intervention for ameliorating stress-recurrent IBD.


Asunto(s)
Enfermedades Inflamatorias del Intestino , Inulina , Ratones , Animales , Inulina/farmacología , Colon/metabolismo , Enfermedades Inflamatorias del Intestino/metabolismo , Inflamación/metabolismo , Citocinas/metabolismo
3.
Arch Microbiol ; 205(2): 66, 2023 Jan 16.
Artículo en Inglés | MEDLINE | ID: mdl-36645481

RESUMEN

Polyhydroxyalkanoate (PHA) is a type of biopolymer produced by most bacteria and archaea, resembling thermoplastic with biodegradability and biocompatibility features. Here, we report the complete genome of a PHA producer, Aquitalea sp. USM4, isolated from Perak, Malaysia. This bacterium possessed a 4.2 Mb circular chromosome and a 54,370 bp plasmid. A total of 4067 predicted protein-coding sequences, 87 tRNA genes, and 25 rRNA operons were identified using PGAP. Based on ANI and dDDH analysis, the Aquitalea sp. USM4 is highly similar to Aquitalea pelogenes. We also identified genes, including acetyl-CoA (phaA), acetoacetyl-CoA (phaB), PHA synthase (phaC), enoyl-CoA hydratase (phaJ), and phasin (phaP), which play an important role in PHA production in Aquitalea sp. USM4. The heterologous expression of phaC1 from Aquitalea sp. USM4 in Cupriavidus necator PHB-4 was able to incorporate six different types of PHA monomers, which are 3-hydroxybutyrate (3HB), 3-hydroxyvalerate (3HV), 4-hydroxybutyrate (4HB), 5-hydroxyvalerate (5HV), 3-hydroxyhexanoate (3HHx) and isocaproic acid (3H4MV) with suitable precursor substrates. This is the first complete genome sequence of the genus Aquitalea among the 22 genome sequences from 4 Aquitalea species listed in the GOLD database, which provides an insight into its genome evolution and molecular machinery responsible for PHA biosynthesis.


Asunto(s)
Betaproteobacteria , Genoma Bacteriano , Polihidroxialcanoatos , Aciltransferasas/genética , Aciltransferasas/metabolismo , Betaproteobacteria/genética , Malasia , Poliésteres/metabolismo
4.
Med Mycol ; 58(5): 679-689, 2020 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-31642483

RESUMEN

NADPH oxidases (Nox) generate reactive oxygen species (ROS) such as superoxide anion radical (O2-) and hydrogen peroxide (H2O2). The pathogenic fungi Candida albicans and Candida glabrata enhance cellular transglutaminase 2 (TG2) activity levels in co-cultured human hepatic cells in a ROS-mediated manner. Deletion of NOX1 (CgNOX1) in C. glabrata blocks the ability of C. glabrata to induce TG2 activity. Here, we investigated whether Nox proteins from C. albicans and Saccharomyces cerevisiae are related with induction of TG2 activity in hepatic cells. C. albicans CFL11 (CaCFL11) was identified as a key factor in this fungus for hepatic TG2 induction in the co-cultures. The cfl11 mutant of C. albicans did not induce TG2 activity in hepatocytes. In addition, overexpression of YNO1, a homolog of CgNOX1, in S. cerevisiae led to induction of ROS generation and TG2 activity in hepatic cells in co-incubation experiments. These findings indicated that a fungal Nox plays a role in enhancing TG2 activity in human hepatocytes and leads to apoptosis.


Asunto(s)
Candida albicans/enzimología , Proteínas de Unión al GTP/metabolismo , NADPH Oxidasas/metabolismo , Saccharomyces cerevisiae/enzimología , Transglutaminasas/metabolismo , Candida albicans/genética , Candida glabrata/enzimología , Candida glabrata/genética , Células Cultivadas , Hepatocitos/metabolismo , Humanos , Peróxido de Hidrógeno/metabolismo , Mutación , NADPH Oxidasas/genética , Proteína Glutamina Gamma Glutamiltransferasa 2 , Especies Reactivas de Oxígeno/metabolismo , Saccharomyces cerevisiae/genética
5.
Biosci Biotechnol Biochem ; 84(7): 1373-1383, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32163007

RESUMEN

PENICILLIUM MARNEFFEI: is a thermally dimorphic fungus that causes penicilliosis, and become the third-most-common opportunistic fungal infection in immunocompromised patients in Southeast Asia. Azoles and amphotericin B have been introduced for the treatment, however, it is important to investigate possible mechanisms of azole resistance for future treatment failure. We identified 177 putative MFS transporters and classified into 17 subfamilies. Among those, members of the Drug:H+ antiporter 1 subfamily are known to confer resistance to antifungals. Out of 39 paralogs, three (encoded by PmMDR1, PmMDR2, and PmMDR3) were heterologously overexpressed in S. cerevisiae AD∆ conferred resistance to various drugs and compounds including azoles, albeit to different degrees. PmMDR1-expressing strain showed resistance to the broadest range of drugs, followed by the PmMDR3, and PmMDR2 conferred weak resistance to a limited range of drugs. We conclude that PmMDR1 and PmMDR3, may be able to serve as multidrug efflux pumps.


Asunto(s)
Subfamilia B de Transportador de Casetes de Unión a ATP/química , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Anfotericina B/farmacología , Antifúngicos/farmacología , Micosis/metabolismo , Talaromyces/metabolismo , Triazoles/farmacología , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Secuencia de Aminoácidos , Anfotericina B/uso terapéutico , Asia Sudoriental/epidemiología , Candida albicans/efectos de los fármacos , Candida albicans/metabolismo , Farmacorresistencia Fúngica/efectos de los fármacos , Humanos , Huésped Inmunocomprometido , Pruebas de Sensibilidad Microbiana , Micosis/tratamiento farmacológico , Micosis/epidemiología , Micosis/microbiología , Filogenia , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Talaromyces/efectos de los fármacos , Transcriptoma , Triazoles/uso terapéutico
6.
Curr Genet ; 65(5): 1251-1261, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31073667

RESUMEN

Glycosylphosphatidylinositol (GPI) is an important compound for the growth of fungi, because GPI-anchored proteins including glycosyltransferases and adhesins are involved in cell-wall integrity, adhesion, and nutrient uptake in this organism. In this study, we examined orf19.5244 in the genome database of the pathogenic fungus Candida albicans, a homologue of the Saccharomyces cerevisiae mannose-ethanolamine phosphotransferase gene, MCD4, which plays a role in GPI synthesis. Expression of this homologue, designated CaMCD4, restored cell growth in a defective conditional mcd4 mutant of S. cerevisiae, Scmcd4t, in which expression of native MCD4 was repressed in the presence of doxycycline (Dox). Analysis of radiolabeled lipids showed that the accumulation of abnormal GPI anchor precursors in Scmcd4t decreased markedly upon expression of CaMCD4. Moreover, we constructed a single mutant (Camcd4/CaMCD4) and a conditional double mutant (Camcd4/Camcd4t) at the MCD4 locus of C. albicans. Repression of CaMCD4 expression by Dox led to a decrease in growth and appearance of abnormal morphology in C. albicans, both in vitro and in a silkworm infection model. These results suggest that CaMcd4p is indispensable for growth of C. albicans both in vitro and in infected hosts and a candidate target for the development of new antifungals.


Asunto(s)
Candida albicans/genética , Candida albicans/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Codón , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulación Fúngica de la Expresión Génica , Glicosilfosfatidilinositoles/metabolismo , Mutación , Fenotipo , Virulencia
7.
Mycoses ; 62(12): 1154-1163, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31519064

RESUMEN

Candida glabrata represents the second-most frequent cause of candidiasis infections of the mucosa, bloodstream and genito-urinary tract in immunocompromised individuals. The incidence of C glabrata infection has increased significantly in the last two decades, mainly due to this species' abilities to resist various antifungal drugs and to form biofilms. We focused on the relationship between biofilm formation and the product of QDR2, a C glabrata member of the major facilitator superfamily (MFS) gene family, given that fungal biofilm formation limits drug penetration and is associated with persistent infection. The fungal cells in biofilms were compared between a C glabrata ∆qdr2 mutant and its wild-type strain. Cells were analysed for metabolism activity and drug susceptibility (using tetrazolium assay), adhesion activity, growth assay and intracellular pH (using flow cytometry). Compared to the wild type, the C glabrata ∆qdr2 showed lower adhesion activity and higher fluconazole susceptibility when assessed as a biofilm. The mutant also showed decreased metabolic activity during biofilm formation. Furthermore, the mutant grew more slowly under neutral-basic pH conditions. The qdr2 deletion in C glabrata resulted in an impaired ability to maintain pH homeostasis, which led in turn to a reduction of cell growth and of adherence to an artificial matrix. These results suggested that the Qdr2p function is needed for proper biofilm formation and biofilm maintenance in C glabrata as well as biofilm drug resistance towards fluconazole. Qdr2p may play an important role in C glabrata's ability to form biofilms on implanted medical devices in human bodies.


Asunto(s)
Biopelículas/crecimiento & desarrollo , Candida glabrata/genética , Candida glabrata/fisiología , Proteínas Fúngicas/genética , Proteínas de Transporte de Membrana/genética , Antifúngicos/farmacología , Biopelículas/efectos de los fármacos , Farmacorresistencia Fúngica/genética , Fluconazol/farmacología , Proteínas Fúngicas/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Pruebas de Sensibilidad Microbiana , Mutación
8.
Mycopathologia ; 184(2): 227-238, 2019 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-30919309

RESUMEN

Malassezia yeasts are opportunistic pathogens associated with a number of skin diseases in animals and humans. The free fatty acids released through these organisms' lipase and phospholipase activities trigger inflammation in the host; thus, these lipase and phospholipase activities are widely recognised as some of the most important factors in Malassezia pathogenesis. In this study, we sought to investigate and examine the relationship between these secreted hydrolytic activities and haemolytic activity in newly isolated Malassezia clinical strains. This characterisation was expected to elucidate pathogenicity of this fungus. We isolated 35 clinical strains of Malassezia spp.; the most frequently isolated species were M. sympodialis and M. furfur. Next, we analysed the hydrolytic activities of all of these clinical isolates; all of these strains (except for one M. dermatis isolate) showed detectable lipase and phospholipase activities against 4-nitrophenyl palmitate and L-α-phosphatidylcholine, dipalmitoyl, respectively. Most of the M. globosa isolates showed higher lipase activities than isolates of other Malassezia species. In terms of phospholipase activity, no significant difference was observed among species of Malassezia, although one isolate of M. globosa showed considerably higher phospholipase activity than the others. All tested strains also exhibited haemolytic activity, both as determined using 5% (v/v) sheep blood agar (halo assay) and by quantitative assay. Although all tested strains showed detectable haemolytic activity, we did not observe an apparent correlation between the secreted lipase and phospholipase activities and haemolytic activity. We infer that the haemolytic activities of Malassezia spp. are mediated by non-enzymatic factor(s) that are present in the secreted samples.


Asunto(s)
Dermatomicosis/microbiología , Hemólisis , Lipasa/análisis , Malassezia/enzimología , Fosfolipasas/análisis , 1,2-Dipalmitoilfosfatidilcolina/metabolismo , Adulto , Animales , Humanos , Lactante , Malassezia/aislamiento & purificación , Palmitatos/metabolismo , Ovinos , Adulto Joven
9.
Curr Genet ; 64(2): 429-441, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-28942495

RESUMEN

Fatty acyl-CoA synthetase (Faa) activates fatty acid (FA) by converting the FA into the CoA ester in the cell. In the present study, we characterized a FAA homologue (CaFAA4) from the opportunistic pathogen Candida albicans. Most organisms can not only synthesize long-chain fatty acyl-CoAs (LCFA-CoAs) endogenously using a fatty acid synthase (Fas) activity but also can uptake long-chain fatty acids (LCFAs) from the extracellular environment and convert them into LCFA-CoAs via a vectorial acylation system. The budding yeast Saccharomyces cerevisiae possesses two LCFA-CoA synthetases, ScFaa1p and ScFaa4p. The disruption of ScFAA1 and ScFAA4 leads to synthetic lethality in the presence of a fatty acid synthesis inhibitor-cerulenin. The homologue-CaFAA4-rescued the lethality of an S. cerevisiae Scfaa1-Scfaa4 double mutant in the presence of cerulenin. On the other hand, a C. albicans faa4 mutant was unable to grow in the presence of cerulenin even if LCFAs were provided exogenously. Moreover, a biofilm analysis showed that the metabolic activity of the Cafaa4 mutant was approximately 40% lower than that of the wild-type parent, even though there was no significant difference in cell number or cell morphology between these strains. Notably, the Cafaa4 mutant showed increased susceptibility to micafungin during biofilm formation, a phenotype that presumably can be attributed to the impaired metabolism of the mutant strain. These results indicated that CaFaa4p is the unique C. albicans Faa protein responsible for activating LCFAs and is involved in the metabolism of biofilms.


Asunto(s)
Acilcoenzima A/genética , Candida albicans/genética , Coenzima A Ligasas/genética , Ácidos Grasos/genética , Proteínas de Saccharomyces cerevisiae/genética , Biopelículas/crecimiento & desarrollo , Transporte Biológico/genética , Candida albicans/crecimiento & desarrollo , Cerulenina/farmacología , Ácidos Grasos/metabolismo , Mutación , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/crecimiento & desarrollo , Homología de Secuencia de Aminoácido
10.
Mycoses ; 60(2): 96-103, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-27597232

RESUMEN

The fungal pathogen Candida albicans undergoes a transition from yeast cells to filamentous cells that is related to its pathogenicity. The complex multicellular processes involved in biofilm formation by this fungus also include this transition. In this work, we investigated the morphological role of the Bgl2 protein (Bgl2p) in the transition to filamentous cells during biofilm formation by C. albicans. Bgl2p has been identified as a ß-1, 3-glucosyltransferase, and transcription of the CaBGL2 gene is upregulated during biofilm formation. We used scanning electron microscopy to observe the microstructure of a bgl2 null mutant during biofilm formation and found a delay in the transition to filamentous cells in the premature phase (24 hours) of biofilm formation. Deletion of the CaBGL2 gene led to a decrease in the expression of CPH2 and TEC1, which encode transcription factors required for the transition to the filamentous form. These findings indicate that Bgl2p plays a role in the transition to filamentous cells during biofilm formation by C. albicans.


Asunto(s)
Biopelículas/crecimiento & desarrollo , Candida albicans/genética , Candida albicans/fisiología , Glucano Endo-1,3-beta-D-Glucosidasa/genética , Factores de Transcripción con Motivo Hélice-Asa-Hélice Básico/genética , Candida albicans/enzimología , Candida albicans/ultraestructura , Candidiasis , Proteínas de Unión al ADN/genética , Proteínas Fúngicas/genética , Eliminación de Gen , Glucano Endo-1,3-beta-D-Glucosidasa/química , Glucano Endo-1,3-beta-D-Glucosidasa/metabolismo , Hifa/genética , Hifa/ultraestructura , Microscopía Electrónica de Rastreo , Mutación , Reacción en Cadena de la Polimerasa , Factores de Transcripción/genética
11.
FEMS Yeast Res ; 16(4)2016 06.
Artículo en Inglés | MEDLINE | ID: mdl-27188883

RESUMEN

The edible, nitrate assimilating, yeast Candida utilis is a commercial food additive, and it is a potentially useful host for heterologous protein expression. A number of ATP-binding cassette (ABC) transporters are multidrug efflux pumps that can cause multidrug resistance in opportunistic pathogens. In order to develop optimal novel antimicrobial agents it is imperative to understand the structure, function and expression of these transporters. With the ultimate aim of developing an alternative yeast host for the heterologous expression of eukaryotic membrane transporters, and to identify ABC transporters potentially associated with C. utilis multidrug resistance, we classified the entire repertoire of 30 C. utilis ABC proteins. We named the open reading frame most similar to the archetype multidrug efflux pump gene C. albicans CDR1 as CuCDR1 Overexpression of CuCDR1 in Saccharomyces cerevisiae ADΔ caused multidrug resistance similar to that of cells overexpressing CaCDR1 Unlike CaCdr1p, however, the C-terminally green fluorescent protein (GFP) tagged CuCdr1p-GFP was functionally impaired and did not properly localize to the plasma membrane. CuCdr1p function could be recovered however by adding a 15 amino acid linker -GAGGSAGGSGGAGAG- between CuCdr1p and the C-terminal GFP tag.


Asunto(s)
Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Candida/genética , Candida/metabolismo , Antifúngicos/farmacología , Clonación Molecular , Farmacorresistencia Fúngica Múltiple , Expresión Génica , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo
13.
Med Mycol ; 54(5): 478-91, 2016 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-26782644

RESUMEN

Penicilliosis caused by the dimorphic fungus Penicillium marneffei is an endemic, AIDS-defining illness and, after tuberculosis and cryptococcosis, the third most common opportunistic infection of AIDS patients in tropical Southeast Asia. Untreated, patients have poor prognosis; however, primary amphotericin B treatment followed by prolonged itraconazole prophylaxis is effective. To identify ATP-binding cassette (ABC) transporters that may play a role in potential multidrug resistance of P. marneffei, we identified and classified all 46 P. marneffei ABC transporters from the genome sequence. PmABC1 and PmABC2 were most similar to the archetype Candida albicans multidrug efflux pump gene CDR1. P. marneffei Abc1p (PmAbc1p) was functionally expressed in Saccharomyces cerevisiae, although at rather low levels, and correctly localized to the plasma membrane, causing cells to be fourfold to eightfold more resistant to azoles and many other xenobiotics than untransformed cells. P. marneffei Abc2p (PmAbc2p) was expressed at similarly low levels, but it had no efflux activity and did not properly localize to the plasma membrane. Interestingly, PmAbc1p mislocalized and lost its transport activity when cells were shifted to 37 °C. We conclude that expression of PmAbc1p in S. cerevisiae confers resistance to several xenobiotics indicating that PmAbc1p may be a multidrug efflux pump.


Asunto(s)
Antifúngicos/metabolismo , Antifúngicos/farmacología , Farmacorresistencia Fúngica , Proteínas de Transporte de Membrana/genética , Proteínas de Transporte de Membrana/metabolismo , Penicillium/genética , Penicillium/metabolismo , Asia Sudoriental , Clonación Molecular , Expresión Génica , Genoma Fúngico , Humanos , Penicillium/aislamiento & purificación , Transporte de Proteínas , Saccharomyces cerevisiae/efectos de los fármacos , Saccharomyces cerevisiae/genética
14.
Mycopathologia ; 180(3-4): 143-51, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26173769

RESUMEN

Malassezia furfur is a dimorphic yeast that is part of the human skin microflora. This fungus is a pathogen of a certain skin diseases, such as pityriasis versicolor, and in rare cases causes systemic infection in neonates. However, the role of dimorphism in the pathogenicity remains unclear. A modified induction medium (IM) was successfully able to induce mycelial growth of M. furfur under both solid and liquid condition. Filamentous elements with branching hyphae were observed when cultured in the IM. Furthermore, addition of bovine fetus serum into the liquid IM did not promote hyphal formation; on the contrary, it retrograded hyphae to the yeast form. Plate-washing assay showed that M. furfur hyphae did not possess the ability of invasive growth. Secretory proteins from both yeast and hyphal forms were isolated, and lipase and protease activities were analyzed. Intriguingly, the hyphal form showed higher activities than those of the yeast form, particularly the protease activity.


Asunto(s)
Perfilación de la Expresión Génica , Lipasa/análisis , Malassezia/citología , Malassezia/enzimología , Micelio/enzimología , Péptido Hidrolasas/análisis , Medios de Cultivo/química , Malassezia/crecimiento & desarrollo , Micelio/crecimiento & desarrollo
15.
Mol Microbiol ; 88(2): 371-81, 2013 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-23448689

RESUMEN

During disseminated infection by the opportunistic pathogen Candida glabrata, uptake of sterols such as serum cholesterol may play a significant role during pathogenesis. The ATP-binding cassette transporter Aus1p is thought to function as a sterol importer and in this study, we show that uptake of exogenous sterols occurred under anaerobic conditions in wild-type cells of C. glabrata but not in AUS1-deleted mutant (aus1Δ) cells. In aerobic cultures, growth inhibition by fluconazole was prevented in the presence of serum, and AUS1 expression was upregulated. Uptake of sterol by azole treated cells required the presence of serum, and sterol alone did not reverse FLC inhibition of growth. However, if iron availability in the growth medium was limited by addition of the iron chelators ferrozine or apo-transferrin, growth of wild-type cells, but not aus1Δ cells, was rescued. In a mouse model of disseminated infection, the C. glabrata aus1Δ strain caused a significantly decreased kidney fungal burden than the wild-type strain or a strain in which AUS1 was restored. We conclude that sterol uptake in C. glabrata can occur in iron poor environment of host tissues and thus may contribute to C. glabrata pathogenesis.


Asunto(s)
Transportadoras de Casetes de Unión a ATP/metabolismo , Candida glabrata/metabolismo , Candida glabrata/patogenicidad , Regulación Fúngica de la Expresión Génica , Hierro/metabolismo , Esteroles/metabolismo , Transportadoras de Casetes de Unión a ATP/genética , Aerobiosis , Anaerobiosis , Animales , Candida glabrata/genética , Candidiasis/microbiología , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Eliminación de Gen , Regulación Fúngica de la Expresión Génica/efectos de los fármacos , Riñón/microbiología , Masculino , Ratones , Ratones Endogámicos BALB C , Bazo/microbiología
16.
Mycoses ; 57(3): 163-8, 2014 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-24028702

RESUMEN

Malassezia species are part of the normal skin flora and are associated with a number of human and animal skin diseases. However, the mechanisms that mediate infection and host-fungal interactions are poorly understood. The haemolytic activity of several microorganisms is considered a factor that contributes to pathogenicity of the organism to humans and animals. This virulence factor was previously identified in several pathogenic fungi that cause systemic mycoses, such as Aspergillus and Candida. In this study, the haemolytic activity of six major Malassezia species, including M. furfur, M. globosa, M. pachydermatis, M. restricta, M. slooffiae and M. sympodialis, was investigated. The haemolytic activity of these species was tested on tryptone soya agar with 5% sheep blood. All the examined Malassezia species produced a halo zone of complete haemolysis. A quantitative analysis of the haemolytic activity was performed by incubating sheep erythrocytes with the extraction from culture of each Malassezia species. Interestingly, M. globosa and M. restricta showed significantly high haemolytic activity compared with the other Malassezia species. In addition, M. globosa also exhibited stable haemolytic activity after treatment at 100 °C and in the presence of some proteases, indicating that this haemolytic factor is different from those of other fungi.


Asunto(s)
Eritrocitos/patología , Hemólisis , Malassezia/aislamiento & purificación , Malassezia/patogenicidad , Animales , Eritrocitos/microbiología , Estudios de Evaluación como Asunto , Humanos , Malassezia/clasificación , Ovinos , Piel/microbiología , Enfermedades de la Piel/microbiología
17.
Nutrients ; 16(14)2024 Jul 13.
Artículo en Inglés | MEDLINE | ID: mdl-39064706

RESUMEN

Circadian rhythm plays an important role in intestinal homeostasis and intestinal immune function. Circadian rhythm dysregulation was reported to induce intestinal microbiota dysbiosis, intestinal barrier disruption, and trigger intestinal inflammation. However, the relationship between intestinal microbiota metabolites and the circadian rhythm of the intestinal barrier was still unclear. Urolithin A (UA), a kind of intestinal microbial metabolite, was selected in this study. Results showed UA influenced on the expression rhythm of the clock genes BMAL1 and PER2 in intestinal epithelial cells. Furthermore, the study investigated the effects of UA on the expression rhythms of clock genes (BMAL1 and PER2) and tight junctions (OCLN, TJP1, and CLND1), all of which were dysregulated by inflammation. In addition, UA pre-treatment by oral administration to female C57BL/6 mice showed the improvement in the fecal IgA concentrations, tight junction expression (Clnd1 and Clnd4), and clock gene expression (Bmal1 and Per2) in a DSS-induced colitis model induced using DSS treatment. Finally, the Nrf2-SIRT1 signaling pathway was confirmed to be involved in UA's effect on the circadian rhythm of intestinal epithelial cells by antagonist treatment. This study also showed evidence that UA feeding showed an impact on the central clock, which are circadian rhythms in SCN. Therefore, this study highlighted the potential of UA in treating diseases like IBD with sleeping disorders by improving the dysregulated circadian rhythms in both the intestinal barrier and the SCN.


Asunto(s)
Ritmo Circadiano , Colitis , Cumarinas , Mucosa Intestinal , Ratones Endogámicos C57BL , Animales , Ritmo Circadiano/efectos de los fármacos , Femenino , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis/metabolismo , Ratones , Cumarinas/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Inflamación , Factor 2 Relacionado con NF-E2/metabolismo , Factores de Transcripción ARNTL/metabolismo , Factores de Transcripción ARNTL/genética , Proteínas Circadianas Period/metabolismo , Proteínas Circadianas Period/genética , Uniones Estrechas/metabolismo , Uniones Estrechas/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Modelos Animales de Enfermedad , Humanos , Sulfato de Dextran , Regulación de la Expresión Génica/efectos de los fármacos , Inmunoglobulina A/metabolismo , Sirtuina 1
18.
Med Mycol ; 51(7): 721-30, 2013 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-23547880

RESUMEN

Malassezia pachydermatis and Candida parapsilosis are recognized as commensal yeasts on the skin of healthy dogs but also causative agents of eborrheic dermatitis, especially in atopic dogs. We determined and compared the susceptibility levels of yeasts isolated from dogs with and without seborrheic dermatitis (SD) using the disk diffusion method (DD) for itraconazole (ITZ), ketoconazole (KTZ), nystatin (NYS), terbinafine (TERB) and 5-fluorocytosine (5-FC) and the broth microdilution method (BMD) for ITZ and KTZ. The reliability between the methods was assessed using an agreement analysis and linear regression. Forty-five M. pachydermatis and 28 C. parapsilosis isolates were identified based on physiological characteristics and an approved molecular analysis. By DD, all tested M. pachydermatis isolates were susceptible to ITZ, KTZ, NYS and TERB but resistant to 5-FC. Only 46 - 60% of the tested C. parapsilosis isolates were susceptible to KTZ, TERB and 5-FC, but ITZ and NYS were effective against all. By BMD, over 95% of M. pachydermatis isolates were susceptible to KTZ and ITZ with an MIC90 < 0.03 and 0.12 µg/ml, respectively. The frequency of KTZ- and ITZ-resistant C. parapsilosis was 29% and 7%, and the MIC90 values were 1 µg/ml and 0.5-1 µg/ml, respectively. Regarding the agreement analysis, 2.2% of minor errors were observed in M. pachydermatis and 0.2-1% of very major errors occurred among C. parapsilosis. There were no significant differences in the yeast resistance rates between dogs with and without SD. KTZ and ITZ were still efficacious for M. pachydermatis but a high rate of KTZ resistant was reported in C. parapsilosis.


Asunto(s)
Antifúngicos/farmacología , Candida/efectos de los fármacos , Candidiasis/veterinaria , Dermatitis Seborreica/veterinaria , Dermatomicosis/veterinaria , Enfermedades de los Perros/microbiología , Malassezia/efectos de los fármacos , Animales , Candida/aislamiento & purificación , Candidiasis/microbiología , Dermatitis Seborreica/microbiología , Dermatomicosis/microbiología , Perros , Farmacorresistencia Fúngica , Malassezia/aislamiento & purificación , Pruebas de Sensibilidad Microbiana
19.
J Infect Chemother ; 19(1): 138-43, 2013 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-23233084

RESUMEN

The pathogenic fungus Candida glabrata is thought to utilize extracellular sterols during infection, but there have been few reports on the sterol uptake mechanisms of this fungus. The addition of serum promoted the growth of C. glabrata cells in the presence of the sterol inhibitor fluconazole, probably as the result of incorporation of cholesterol from serum. We demonstrated that lipoprotein-deficient serum, in which most of the cholesterol was eliminated, could not rescue the growth of fluconazole-treated C. glabrata cells, but it successfully promoted the expression of the sterol transporter gene AUS1. After supplementation of free cholesterol to lipoprotein-deficient serum, the serum was again competent to promote the growth of fluconazole-treated C. glabrata. The serum-mediated growth rescue from fluconazole inhibition was observed in the nonpathogenic yeast Saccharomyces cerevisiae when it was followed by the activation of anaerobic sterol uptake. These results suggested that serum cholesterol was incorporated into yeast cells to compensate for sterol depletion when sterol uptake was activated. The uptake of serum cholesterol could support the growth of C. glabrata cells during bloodstream infections.


Asunto(s)
Transportadoras de Casetes de Unión a ATP/metabolismo , Antifúngicos/farmacología , Candida glabrata/crecimiento & desarrollo , Colesterol/metabolismo , Colesterol/farmacología , Fluconazol/farmacología , Transportadoras de Casetes de Unión a ATP/genética , Antifúngicos/metabolismo , Candida glabrata/efectos de los fármacos , Candida glabrata/metabolismo , Colesterol/sangre , Fluconazol/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Regulación Fúngica de la Expresión Génica , Esteroles/biosíntesis , Esteroles/metabolismo
20.
J Fungi (Basel) ; 10(1)2023 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-38248926

RESUMEN

Most previous studies on fungal NADPH oxidases (Nox) focused on multicellular fungi and highlighted the important roles of Nox-derived reactive oxygen species (ROS) in cellular differentiation and signaling communication. However, there are few reports about Nox in unicellular fungi. A novel NOX ortholog, CAGL0K05863g (named CgNOX1), in Candida glabrata was investigated in this study. Deletion of CgNOX1 led to a decrease in both intracellular and extracellular ROS production. In addition, the Cgnox1∆ mutant exhibited hypersensitivity to hydrogen peroxide and menadione. Also, the wild-type strain showed higher levels of both CgNOX1 mRNA expression and ROS production under oxidative stress. Moreover, the absence of CgNOX1 resulted in impaired ferric reductase activity. Although there was no effect on in vitro biofilm formation, the CgNOX1 mutant did not produce hepatic apoptosis, which might be mediated by fungal Nox-derived ROS during co-incubation. Together, these results indicated that the novel NOX gene plays important roles in unicellular pathogenic C. glabrata and its interaction with host cells.

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