Publications by authors named "Tamas Papp"

83 Publications

Global guideline for the diagnosis and management of rare yeast infections: an initiative of the ECMM in cooperation with ISHAM and ASM.

Lancet Infect Dis 2021 Aug 19. Epub 2021 Aug 19.

Department of Clinical Microbiology and Immunology, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

Uncommon, or rare, yeast infections are on the rise given increasing numbers of patients who are immunocompromised or seriously ill. The major pathogens include those of the genera Geotrichum, Saprochaete, Magnusiomyces, and Trichosporon (ie, basidiomycetes) and Kodamaea, Malassezia, Pseudozyma (ie, now Moesziomyces or Dirkmeia), Rhodotorula, Saccharomyces, and Sporobolomyces (ie, ascomycetes). A considered approach to the complex, multidisciplinary management of infections that are caused by these pathogens is essential to optimising patient outcomes; however, management guidelines are either region-specific or require updating. In alignment with the One World-One Guideline initiative to incorporate regional differences, experts from diverse geographical regions analysed publications describing the epidemiology and management of the previously mentioned rare yeasts. This guideline summarises the consensus recommendations with regards to the diagnostic and therapeutic options for patients with these rare yeast infections, with the intent of providing practical assistance in clinical decision making. Because there is less clinical experience of patients with rare yeast infections and studies on these patients were not randomised, nor were groups compared, most recommendations are not robust in their validation but represent insights by use of expert opinions and in-vitro susceptibility results. In this Review, we report the key features of the epidemiology, diagnosis, antifungal susceptibility, and treatment outcomes of patients with Geotrichum, Saprochaete, Magnusiomyces, and Trichosporon spp infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S1473-3099(21)00203-6DOI Listing
August 2021

In Vitro Activity of Selected Phenolic Compounds against Planktonic and Biofilm Cells of Food-Contaminating Yeasts.

Foods 2021 Jul 17;10(7). Epub 2021 Jul 17.

Department of Microbiology, Faculty of Science and Informatics, University of Szeged, Közép Fasor 52, H-6726 Szeged, Hungary.

Phenolic compounds are natural substances that can be obtained from plants. Many of them are potent growth inhibitors of foodborne pathogenic microorganisms, however, phenolic activities against spoilage yeasts are rarely studied. In this study, planktonic and biofilm growth, and the adhesion capacity of , , and spoilage yeasts were investigated in the presence of hydroxybenzoic acid, hydroxycinnamic acid, stilbene, flavonoid and phenolic aldehyde compounds. The results showed significant anti-yeast properties for many phenolics. Among the tested molecules, cinnamic acid and vanillin exhibited the highest antimicrobial activity with minimum inhibitory concentration (MIC) values from 500 µg/mL to 2 mg/mL. Quercetin, (-)-epicatechin, resveratrol, 4-hydroxybenzaldehyde, -coumaric acid and ferulic acid were also efficient growth inhibitors for certain yeasts with a MIC of 2 mg/mL. The , and biofilms were the most sensitive to the phenolics, while the biofilm was quite resistant against the activity of the compounds. Fluorescence microscopy revealed disrupted biofilm matrix on glass surfaces in the presence of certain phenolics. Highest antiadhesion activity was registered for cinnamic acid with inhibition effects between 48% and 91%. The active phenolics can be natural interventions against food-contaminating yeasts in future preservative developments.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/foods10071652DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8307438PMC
July 2021

Characterization of Three Pleiotropic Drug Resistance Transporter Genes and Their Participation in the Azole Resistance of .

Front Cell Infect Microbiol 2021 14;11:660347. Epub 2021 Apr 14.

Department of Microbiology, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary.

Mucormycosis is a life-threatening opportunistic infection caused by certain members of the fungal order Mucorales. This infection is associated with high mortality rate, which can reach nearly 100% depending on the underlying condition of the patient. Treatment of mucormycosis is challenging because these fungi are intrinsically resistant to most of the routinely used antifungal agents, such as most of the azoles. One possible mechanism of azole resistance is the drug efflux catalyzed by members of the ATP binding cassette (ABC) transporter superfamily. The pleiotropic drug resistance (PDR) transporter subfamily of ABC transporters is the most closely associated to drug resistance. The genome of encodes eight putative PDR-type transporters. In this study, transcription of the eight genes has been analyzed after azole treatment. Only the showed increased transcript level in response to all tested azoles. Deletion of this gene caused increased susceptibility to posaconazole, ravuconazole and isavuconazole and altered growth ability of the mutant. In the deletion mutant, transcript level of and significantly increased. Deletion of and was also done to create single and double knock out mutants for the three genes. After deletion of and , growth ability of the mutant strains decreased, while deletion of resulted in increased sensitivity against posaconazole, ravuconazole and isavuconazole. Our result suggests that the regulation of the eight genes is interconnected and and participates in the resistance of the fungus to posaconazole, ravuconazole and isavuconazole.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcimb.2021.660347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079984PMC
July 2021

β-Galactosidase-Producing Isolates in Mucoromycota: Screening, Enzyme Production, and Applications for Functional Oligosaccharide Synthesis.

J Fungi (Basel) 2021 Mar 19;7(3). Epub 2021 Mar 19.

Department of Microbiology, Faculty of Science and Informatics, University of Szeged, Közép fasor 52, H-6726 Szeged, Hungary.

β-Galactosidases of Mucoromycota are rarely studied, although this group of filamentous fungi is an excellent source of many industrial enzymes. In this study, 99 isolates from the genera , , , , and , were screened for their β-galactosidase activity using a chromogenic agar approach. Ten isolates from the best producers were selected, and the activity was further investigated in submerged (SmF) and solid-state (SSF) fermentation systems containing lactose and/or wheat bran substrates as enzyme production inducers. Wheat bran proved to be efficient for the enzyme production under both SmF and SSF conditions, giving maximum specific activity yields from 32 to 12,064 U/mg protein and from 783 to 22,720 U/mg protein, respectively. Oligosaccharide synthesis tests revealed the suitability of crude β-galactosidases from Szeged Microbiological Collection (SZMC) 11360 and SZMC 11025 to catalyze transgalactosylation reactions. In addition, the crude enzyme extracts had transfructosylation activity, resulting in the formation of fructo-oligosaccharide molecules in a sucrose-containing environment. The maximal oligosaccharide concentration varied between 0.0158 and 2.236 g/L depending on the crude enzyme and the initial material. Some oligosaccharide-enriched mixtures supported the growth of probiotics, indicating the potential of the studied enzyme extracts in future prebiotic synthesis processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jof7030229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8003776PMC
March 2021

An intra-abdominal desmoid tumor.

Acta Radiol Open 2021 Feb 22;10(2):2058460121992455. Epub 2021 Feb 22.

Department of Medical Imaging, Faculty of Medicine, University of Debrecen, Hungary.

Desmoid tumor is a very rare neoplasm which develops from fibroblasts. These tumors do not have the ability to metastasize, but they can cause significant morbidity and mortality by local invasion and they are prone to local recurrence. We present a case of an aggressive fibromatosis in a 28-year-old male patient with no previous medical history. The tumor was in the retroperitoneum and eventually caused perforation of the coecum. During the operation, no metastasis was found; however, local lymphadenopathy was seen. After the surgical resection, no adjuvant therapy (radio or chemotherapy) was given to the patient and on follow-up (after three years), no recurrence was observed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/2058460121992455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7903839PMC
February 2021

Effective connectivity differences in motor network during passive movement of paretic and non-paretic ankles in subacute stroke patients.

PeerJ 2020 26;8:e8942. Epub 2020 May 26.

Faculty of Medicine, Department of Medical Imaging, Division of Nuclear Medicine and Translational Imaging, University of Debrecen, Debrecen, Hajdú-Bihar, Hungary.

Background: A better understanding of the neural changes associated with paresis in stroke patients could have important implications for therapeutic approaches. Dynamic Causal Modeling (DCM) for functional magnetic resonance imaging (fMRI) is commonly used for analyzing effective connectivity patterns of brain networks due to its significant property of modeling neural states behind fMRI signals. We applied this technique to analyze the differences between motor networks (MNW) activated by continuous passive movement (CPM) of paretic and non-paretic ankles in subacute stroke patients. This study aimed to identify CPM induced connectivity characteristics of the primary sensory area (S1) and the differences in extrinsic directed connections of the MNW and to explain the hemodynamic differences of brain regions of MNW.

Methods: For the network analysis, we used ten stroke patients' task fMRI data collected under CPMs of both ankles. Regions for the MNW, the primary motor cortex (M1), the premotor cortex (PM), the supplementary motor area (SMA) and the S1 were defined in a data-driven way, by independent component analysis. For the network analysis of both CPMs, we compared twelve models organized into two model-families, depending on the S1 connections and input stimulus modeling. Using DCM, we evaluated the extrinsic connectivity strengths and hemodynamic parameters of both stimulations of all patients.

Results: After a statistical comparison of the extrinsic connections and their modulations of the "best model", we concluded that three contralateral self-inhibitions (cM1, cS1 and cSMA), one contralateral inter-regional connection (cSMA→cM1), and one interhemispheric connection (cM1→iM1) were significantly different. Our research shows that hemodynamic parameters can be estimated with the Balloon model using DCM but the parameters do not change with stroke.

Conclusions: Our results confirm that the DCM-based connectivity analyses combined with Bayesian model selection may be a useful technique for quantifying the alteration or differences in the characteristics of the motor network in subacute stage stroke patients and in determining the degree of MNW changes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.7717/peerj.8942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7258895PMC
May 2020

CRISPR-Cas9-Based Mutagenesis of the Mucormycosis-Causing Fungus .

Int J Mol Sci 2020 May 25;21(10). Epub 2020 May 25.

MTA-SZTE Fungal Pathogenicity Mechanisms Research Group, Hungarian Academy of Sciences-University of Szeged, 6726 Szeged, Hungary.

is considered as one of the most frequent agents of mucormycosis. The lack of efficient genetic manipulation tools hampers the characterization of the pathomechanisms and virulence factors of this opportunistic pathogenic fungus. Although such techniques have been described for certain species, the performance of targeted mutagenesis and the construction of stable transformants have remained a great challenge in Mucorales fungi. In the present study, a plasmid-free CRISPR-Cas9 system was applied to carry out a targeted gene disruption in . The described method is based on the non-homologous end-joining repair of the double-strand break caused by the Cas9 enzyme. Using this method, short, one-to-five nucleotide long-targeted deletions could be induced in the orotidine 5'-phosphate decarboxylase gene () and, as a result, uracil auxotrophic strains were constructed. These strains are applicable as recipient strains in future gene manipulation studies. As we know, this is the first genetic modification of this clinically relevant fungus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21103727DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279233PMC
May 2020

Response of Human Neutrophil Granulocytes to the Hyphae of the Emerging Fungal Pathogen .

Pathogens 2020 Mar 21;9(3). Epub 2020 Mar 21.

MTA-SZTE Fungal Pathogenicity Mechanisms Research Group, Hungarian Academy of Sciences-University of Szeged, 6726 Szeged, Hungary.

is an ascomycete filamentous fungus causing local and invasive phaeohyphomycoses in both immunocompromised and immunocompetent patients. Neutrophils are crucial participants of the first line host defense against fungal infections. They migrate to the infected site and eliminate the infectious agents by various mechanisms including phagocytoses, oxidative damage, or formation of neutrophil extracellular trap (NET). Neutropenia may be a risk factor for phaeohyphomycoses, and restoration of the neutrophil function can improve the outcome of the infection. In the present study, interaction of primary human neutrophil granulocytes with the hyphae was examined and compared to that with the well characterized filamentous fungal pathogen . Neutrophils could recognize the serum opsonized hyphae of and attach to them. Myeloperoxidase release was also activated by a soluble factor present in the culture supernatant of the fungus. Induction of the oxidative burst was found to depend on serum opsonization of the hyphae. Although extracellular hydrogen peroxide production was induced, the fungus efficiently blocked the oxidative burst by acidifying the reaction environment. This blockage also affected the NET forming ability of the neutrophils.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/pathogens9030235DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157731PMC
March 2020

Plant Phenolics and Phenolic-Enriched Extracts as Antimicrobial Agents against Food-Contaminating Microorganisms.

Antioxidants (Basel) 2020 Feb 18;9(2). Epub 2020 Feb 18.

Department of Microbiology, Faculty of Science and Informatics, University of Szeged, Közép fasor 52, H-6726 Szeged, Hungary.

Phenolic compounds and extracts with bioactive properties can be obtained from many kinds of plant materials. These natural substances have gained attention in the food research as possible growth inhibitors of foodborne pathogenic and spoilage bacteria. Many phenolic-enriched plant extracts and individual phenolics have promising anti-quorum sensing potential as well and can suppress the biofilm formation and toxin production of food-related pathogens. Various studies have shown that plant phenolics can substitute or support the activity of synthetic food preservatives and disinfectants, which, by the way, can provoke serious concerns in consumers. In this review, we will provide a brief insight into the bioactive properties, i.e., the antimicrobial, anti-quorum sensing, anti-biofilm and anti-enterotoxin activities, of plant phenolic extracts and compounds, with special attention to pathogen microorganisms that have food relation. Carbohydrase aided applications to improve the antimicrobial properties of phenolic extracts are also discussed.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/antiox9020165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070704PMC
February 2020

New Species of the Genus : and from Fungal Keratitis Cases in South India.

Pathogens 2019 Dec 20;9(1). Epub 2019 Dec 20.

Department of Microbiology, Faculty of Science and Informatics, University of Szeged, 6726 Szeged, Hungary.

Members of the genus are melanin-producing dematiaceous fungi of increasing clinical importance as causal agents of both local and invasive infections. This study contributes to the taxonomical and clinical knowledge of this genus by describing two new species based on isolates from corneal scrapings of South Indian fungal keratitis patients. The phylogeny of the genus was updated based on three phylogenetic markers: the internal transcribed spacer (ITS) region of the ribosomal RNA gene cluster as well as fragments of the glyceraldehyde-3-phosphate dehydrogenase () and translation elongation factor 1-α () genes. The maximum likelihood phylogenetic tree constructed from the alignment of the three concatenated loci revealed that the examined isolates are representing two new, yet undescribed, species. Examination of colony and microscopic morphology revealed differences between the two species as well as between the new species and their close relatives. The new species were formally described as N. Kiss & S. Kocsubé sp. nov. and N. Kiss & S. Kocsubé sp. nov. Antifungal susceptibility testing by the broth microdilution method of CLSI (Clinical & Laboratory Standards Institute) revealed that the type strain of is less susceptible to a series of antifungals than the strains.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/pathogens9010009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168623PMC
December 2019

Characterization of Strains From Human Keratomycoses: Molecular Identification, Antifungal Susceptibility Patterns and Cyclopiazonic Acid Producing Abilities.

Front Microbiol 2019 9;10:2249. Epub 2019 Oct 9.

MTA-SZTE "Lendület" Fungal Pathogenicity Mechanisms Research Group, Szeged, Hungary.

appears to be an emerging aetiological agent of human keratomycoses in South India. The investigated strains were isolated from six suspected fungal keratitis patients attending a tertiary care eye hospital in Coimbatore (Tamil Nadu, India), and were initially identified by the microscopic examinations of the scrapings and the cultures. Our data suggest that could be easily overlooked when identification is carried out based on morphological characteristics alone, while the sequence analysis of the calmodulin gene can be used successfully to recognize this species accurately. According to the collected clinical data, ocular trauma is a common risk factor for the infection that gradually developed from mild to severe ulcers and could be healed with an appropriate combined antifungal therapy. Antifungal susceptibility testing revealed that strains are susceptible to the most commonly used topical or systemic antifungal agents (i.e., econazole, itraconazole and ketoconazole) except for natamycin. Moreover, natamycin proved to be similarly less effective than the azoles against in our drug interaction tests, as the predominance of indifferent interactions was revealed between natamycin and econazole and between natamycin and itraconazole as well. Four and five isolates of were confirmed to produce cyclopiazonic acid (CPA) in RPMI-1640 - which is designed to mimic the composition of human extracellular fluids - and in yeast extract sucrose (YES) medium, respectively, which is a widely used culture medium for testing mycotoxin production. Although a ten times lower mycelial biomass was recorded in RPMI-1640 than in YES medium, the toxin contents of the samples were of the same order of magnitude in both types of media. There might be a relationship between the outcome of infections and the toxigenic properties of the infecting fungal strains. However, this remains to be investigated in the future.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2019.02249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6794953PMC
October 2019

Detection and Molecular Characterization of Novel dsRNA Viruses Related to the Family in .

Front Cell Infect Microbiol 2019 11;9:249. Epub 2019 Jul 11.

Department of Microbiology, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary.

is an oleaginous fungus belonging to the Mucoromycotina subphylum. Our group had previously detected four double-stranded RNA (dsRNA) bands in the NRRL 1296 strain by gel electrophoresis. Here we describe the molecular characterization of its dsRNA elements as well as the discovery of four novel dsRNA viruses: Umbelopsis ramanniana virus 1 (UrV1), Umbelopsis ramanniana virus 2 (UrV2), Umbelopsis ramanniana virus 3 (UrV3), and Umbelopsis ramanniana virus 4 (UrV4). Full genomes of UrV1, UrV3, and UrV4 were determined using the full-length amplification of cDNAs (FLAC) technique; they contain two open reading frames (ORF), which putatively encode the coat protein (CP) and the RNA dependent RNA polymerase (RdRp), respectively. In case of UrV2, a partial ORF encoding a partial RdRp gene could be determined. Based on the phylogeny inferred from the RdRp sequences, UrV1 and UrV4 belong to the genus , while UrV2 may belong to the genus . UrV3 nested to a novel, unclassified group of , which is related to the genus . Hybridization analysis revealed that the dsRNA molecules of UrV1 and UrV4 correspond to the same 5.0-kbp electrophoretic band, whilst the probe for the UrV3 hybridized to the largest, 5.3-kbp and the 3.0-kbp bands of the dsRNA pattern of . Interestingly, the probe for the UrV2 sequence did not hybridized to any dsRNA bands, but it could be amplified from the isolated 3.0-kbp fragment. By transmission electron microscopy, two different isometric virus particles with about 50 and 35 nm in diameter were detected in NRRL 1296 indicating that this strain harbor multiple viruses. Beside , dsRNA elements were also detected in other isolates with different patterns consisting of 2 to 4 discrete and different sized (0.7-5.3-kbp) dsRNA molecules. Based on a hybridization analysis with UrV1 CP and RdRp probes, the bands with the size of around 5.0-kbp, which were present in all tested strains, are presumed as possible full mycovirus genomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcimb.2019.00249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6644447PMC
July 2020

ECMM CandiReg-A ready to use platform for outbreaks and epidemiological studies.

Mycoses 2019 Oct 1;62(10):920-927. Epub 2019 Aug 1.

Department of Infectious Diseases, Nacional Institute of Health Dr. Ricardo Jorge - Reference Unit for Parasitic and Fungal Infections, Lisbon, Portugal.

Background: Recent outbreaks of Candida auris further exemplify that invasive Candida infections are a substantial threat to patients and healthcare systems. Even short treatment delays are associated with higher mortality rates. Epidemiological shifts towards more resistant Candida spp. require careful surveillance.

Objectives: Triggered by the emergence of C auris and by increasing antifungal resistance rates the European Confederation of Medical Mycology developed an international Candida Registry (FungiScope™ CandiReg) to allow contemporary multinational surveillance.

Methods: CandiReg serves as platform for international cooperation to enhance research regarding invasive Candida infections. CandiReg uses the General Data Protection Regulation compliant data platform ClinicalSurveys.net that holds the electronic case report forms (eCRF). Data entry is supported via an interactive macro created by the software that can be accessed via any Internet browser.

Results: CandiReg provides an eCRF for invasive Candida infections that can be used for a variety of studies from cohort studies on attributable mortality to evaluations of guideline adherence, offering to the investigators of the 28 ECMM member countries the opportunity to document their cases of invasive Candida infection. CandiReg allows the monitoring of epidemiology of invasive Candida infections, including monitoring of multinational outbreaks. Here, we describe the structure and management of the CandiReg platform.

Conclusion: CandiReg supports the collection of clinical information and isolates to improve the knowledge on epidemiology and eventually to improve management of invasive Candida infections. CandiReg promotes international collaboration, improving the availability and quality of evidence on invasive Candida infection and contributes to improved patient management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/myc.12963DOI Listing
October 2019

Host metabolite producing endophytic fungi isolated from Hypericum perforatum.

PLoS One 2019 21;14(5):e0217060. Epub 2019 May 21.

Department of Microbiology, Faculty of Science and Informatics, University of Szeged, Szeged, Hungary.

In the present study, endophytic fungi have been isolated from various parts of the medicinal herb Hypericum perforatum (St. John's Wort), which is known as a source of medically important metabolites. The isolated strains were cultured in liquid media and their ability to synthesize hypericin, the secondary metabolite of the host and its suspected precursor, emodin was tested analyzing the extracts of the fermentation broth and the mycelia. The HPLC-UV analysis of the chloroform/methanol extracts of the mycelia revealed that three isolates were able to produce emodin (SZMC 23771, 19.9 ng/mg; SZMC 23772, 20.8 ng/mg; SZMC 23769, 427.9 ng/mg) and one of them also could synthesize hypericin (SZMC 23769, 320.4 ng/mg). These results were also confirmed via UHPLC-HRMS technique both in full scan and MS/MS mode. The strains producing only emodin belong to the section Alternata of the genus Alternaria, while the isolate producing both metabolites was identified as Epicoccum nigrum. The mycelial extracts of E. nigrum and the Alternaria sp. SZMC 23772 showed higher inhibitory activities in the antimicrobial tests against the six selected bacteria compared to the hypericin and emodin standards in the applied concentration (100 μg/mL), while in case of the Alternaria sp. SZMC 23771 lower inhibition activities were observed on Staphylococcus aureus and Streptomyces albus than the pure compounds.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0217060PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6529008PMC
February 2020

CRISPR-Cas9-mediated disruption of the HMG-CoA reductase genes of Mucor circinelloides and subcellular localization of the encoded enzymes.

Fungal Genet Biol 2019 08 13;129:30-39. Epub 2019 Apr 13.

MTA-SZTE "Lendület" Fungal Pathogenicity Mechanisms Research Group, Közép fasor 52., 6726 Szeged, Hungary; Interdisciplinary Excellence Centre, Department of Microbiology, University of Szeged, Közép fasor 52., 6726 Szeged, Hungary; Department of Microbiology, Faculty of Science and Informatics, University of Szeged, Közép fasor 52., 6726 Szeged, Hungary. Electronic address:

Terpenoid compounds, such as sterols, carotenoids or the prenyl groups of various proteins are synthesized via the mevalonate pathway. A rate-limiting step of this pathway is the conversion of 3-methylglutaryl-CoA (HMG-CoA) to mevalonic acid catalyzed by the HMG-CoA reductase. Activity of this enzyme may affect several biological processes, from the synthesis of terpenoid metabolites to the adaptation to various environmental conditions. In this study, the three HMG-CoA reductase genes (i.e. hmgR1, hmgR2 and hmgR3) of the β-carotene producing filamentous fungus, Mucor circinelloides were disrupted individually and simultaneously by a recently developed in vitro plasmid-free CRISPR-Cas9 method. Examination of the mutants revealed that the function of hmgR2 and hmgR3 are partially overlapping and involved in the general terpenoid biosynthesis. Moreover, hmgR2 seemed to have a special role in the ergosterol biosynthesis. Disruption of all three genes affected the germination ability of the spores and the sensitivity to hydrogen peroxide. Disruption of the hmgR1 gene had no effect on the ergosterol production and the sensitivity to statins but caused a reduced growth at lower temperatures. By confocal fluorescence microscopy using strains expressing GFP-tagged HmgR proteins, all three HMG-CoA reductases were localized in the endoplasmic reticulum.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.fgb.2019.04.008DOI Listing
August 2019

Interactions of With Species Frequently Associated With Cystic Fibrosis.

Front Microbiol 2019 6;10:441. Epub 2019 Mar 6.

MTA-SZTE "Lendület" Fungal Pathogenicity Mechanisms Research Group, Szeged, Hungary.

Members of the species complex are the second most frequently isolated pathogens after from cystic fibrosis (CF) patients with fungal pulmonary infections. Even so, the main risk factors for the infection are unrevealed. According to previous studies, bacterial infections might reduce the risk of a fungal infection, but an antibacterial therapy may contribute to the airway colonization by several fungal pathogens. Furthermore, corticosteroids, which are often used to reduce lung inflammation in children and adults with CF, are also proved to enhance the growth of . Considering all the above discussed points, we aimed to test how influences the growth of scedosporia and to investigate the potential effect of commonly applied antibacterial agents and corticosteroids on species. Direct interactions between fungal and bacterial strains were tested using the disk inhibition method. Indirect interactions via volatile compounds were investigated by the plate-in-plate method, while the effect of bacterial media-soluble molecules was tested using a modified cellophane assay and also in liquid culture media conditioned by . To test the effect of bacterial signal molecules, antibacterial agents and corticosteroids on the fungal growth, the broth microdilution method was used. We also investigated the germination ability of conidia in the presence of pyocyanin and diffusible signal factor by microscopy. According to our results, either inhibited or enhanced the growth of scedosporia depending on the culture conditions and the mode of interactions. When the two pathogens were cultured physically separately from each other in the plate-in-plate tests, the presence of the bacteria was able to stimulate the growth of several fungal isolates. While in direct physical contact, bacterial strains inhibited the fungal growth. This effect might be attributed to bacterial signal molecules, which also proved to inhibit the germination and growth of scedosporia. In addition, antibacterial agents showed growth-promoting, while corticosteroids exhibited growth inhibitory effect on several isolates. These data raise the possibility that a infection or a previously administered antibacterial therapy might be able to increase the chance of a colonization in a CF lung.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2019.00441DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6414507PMC
March 2019

Megaphylogeny resolves global patterns of mushroom evolution.

Nat Ecol Evol 2019 04 18;3(4):668-678. Epub 2019 Mar 18.

Natural History Museum, Slovak National Museum, Bratislava, Slovakia.

Mushroom-forming fungi (Agaricomycetes) have the greatest morphological diversity and complexity of any group of fungi. They have radiated into most niches and fulfil diverse roles in the ecosystem, including wood decomposers, pathogens or mycorrhizal mutualists. Despite the importance of mushroom-forming fungi, large-scale patterns of their evolutionary history are poorly known, in part due to the lack of a comprehensive and dated molecular phylogeny. Here, using multigene and genome-based data, we assemble a 5,284-species phylogenetic tree and infer ages and broad patterns of speciation/extinction and morphological innovation in mushroom-forming fungi. Agaricomycetes started a rapid class-wide radiation in the Jurassic, coinciding with the spread of (sub)tropical coniferous forests and a warming climate. A possible mass extinction, several clade-specific adaptive radiations and morphological diversification of fruiting bodies followed during the Cretaceous and the Paleogene, convergently giving rise to the classic toadstool morphology, with a cap, stalk and gills (pileate-stipitate morphology). This morphology is associated with increased rates of lineage diversification, suggesting it represents a key innovation in the evolution of mushroom-forming fungi. The increase in mushroom diversity started during the Mesozoic-Cenozoic radiation event, an era of humid climate when terrestrial communities dominated by gymnosperms and reptiles were also expanding.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41559-019-0834-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6443077PMC
April 2019

Expression Vectors and Gene Fusions for the Directed Modification of the Carotenoid Biosynthesis Pathway in Mucor circinelloides.

Methods Mol Biol 2018 ;1852:239-256

Department of Microbiology, University of Szeged, Szeged, Hungary.

Several fungal species, particularly some included in the Mucoromycotina, have been used to develop fermentation processes for the production of β-carotene. Oxygenated derivatives of β-carotene (xanthophylls) are desirable value-added products, and the preference by the market of carotenoids from biological sources has increased the research in different carotenoid-producing organisms. We currently use Mucor circinelloides f. lusitanicus as a model organism to develop strains with an increased content of new and more valuable carotenoids. The main carotenoid accumulated by M. circinelloides is β-carotene, although it has some hydroxylase activity and produces low amounts of zeaxanthin. On the other hand, in astaxanthin-producing organisms two enzymatic activities are required for the production of astaxanthin from β-carotene: a hydroxylase and a ketolase. In this chapter, we delineate part of our efforts to construct genetically modified strains that could advance in the improvement of carotenoid accumulation by this fungus and the diversification of its carotenoid content. Accordingly, we describe detailed and empirically tested protocols for the construction of functional expression vectors and gene fusions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-1-4939-8742-9_14DOI Listing
May 2019

South Indian Isolates of the Species Complex From Clinical and Environmental Samples: Identification, Antifungal Susceptibilities, and Virulence.

Front Microbiol 2018 23;9:1052. Epub 2018 May 23.

MTA-SZTE "Lendület" Fungal Pathogenicity Mechanisms Research Group, Szeged, Hungary.

Members of the species complex (FSSC) are the most frequently isolated fusaria from soil. Moreover, this complex solely affects more than 100 plant genera, and is also one of the major opportunistic human pathogenic filamentous fungi, being responsible for approximately two-third of fusariosis cases. Mycotic keratitis due to species is among the leading causes of visual impairment and blindness in South India, but its management is still challenging due to the poor susceptibility of the isolates to conventional antifungal drugs. Aims of the present study were to isolate South Indian clinical and environmental FSSC strains and identify them to species level, to determine the actual trends in their susceptibilities to antifungal therapeutic drugs and to compare the virulence of clinical and environmental FSSC members. Based on the partial sequences of the translation elongation factor 1α gene, the majority of the isolates-both from keratomycosis and environment-were confirmed as , followed by and . antifungal susceptibilities to commonly used azole, allylamine and polyene antifungals were determined by the CLSI M38-A2 broth microdilution method. The first generation triazoles, fluconazole and itraconazole proved to be ineffective against all isolates tested. This phenomenon has already been described before, as fusaria are intrinsically resistant to them. However, our results indicated that despite the intensive agricultural use of azole compounds, fusaria have not developed resistance against the imidazole class of antifungals. In order to compare the virulence of different FSSC species from clinical and environmental sources, a model was used. MyD88 mutant flies having impaired immune responses were highly susceptible to all the examined fusaria. In wild-type flies, one and two strains also reduced the survival significantly. Pathogenicity seemed to be independent from the origin of the isolates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmicb.2018.01052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974209PMC
May 2018

An Organic Solvent-Tolerant Lipase with Both Hydrolytic and Synthetic Activities from the Oleaginous Fungus Mortierella echinosphaera.

Int J Mol Sci 2018 Apr 10;19(4). Epub 2018 Apr 10.

Department of Microbiology, Faculty of Science and Informatics, University of Szeged, Közép fasor 52, H-6726 Szeged, Hungary.

Lipase enzymes of the oleaginous fungal group are rarely studied. However, considering that most commercial lipases are derived from filamentous fungal sources, their investigation can contribute to the cost-effective development of new biotechnological processes. Here, an extracellular lipase with a molecular mass of 30 kDa was isolated from CBS 575.75 and characterized. The purified lipase exhibited an optimal -nitrophenyl palmitate (NPP)-hydrolyzing activity at 25 °C and pH 6.6-7.0 and proved to be highly stable at temperatures up to 40 °C and under broad pH conditions. The enzyme was active under low temperatures, retaining 32.5% of its activity at 10 °C, and was significantly stable in polar and non-polar organic solvents. The , , and for NPP were 0.336 mM, 30.4 μM/min, and 45.7 1/min for NPP and 0.333 mM, 36.9 μM/min, and 55.6 1/min for NP-decanoate, respectively. The NPP hydrolysis was inhibited by Hg, -bromosuccinimide, and sodium dodecyl sulfate, while ethylenediaminetetraacetic acid and metal ions, such as Ca, Mg, Na⁺, and K⁺ enhanced the activity. The purified lipase had non-regioselective activity and wide substrate specificity, showing a clear preference for medium-chained -nitrophenyl esters. Besides its good transesterification activity, the enzyme appeared as a suitable biocatalyst to operate selective esterification reactions to long-chained alkyl esters. Adsorption to Accurel MP1000 improved the storage stability of the enzyme at 5 °C. The immobilized lipase displayed tolerance to a non-aqueous environment and was reusable for up to five cycles without significant loss in its synthetic and hydrolytic activities. These findings confirm the applicability of both the free and the immobilized enzyme preparations in future research.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms19041129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5979600PMC
April 2018

Exophiala dermatitidis Endophthalmitis: Case Report and Literature Review.

Mycopathologia 2018 Jun 27;183(3):603-609. Epub 2018 Jan 27.

Department of Microbiology, Faculty of Science and Informatics, University of Szeged, Közép Fasor 52, Szeged, 6726, Hungary.

We report a case of a 59-year-old male patient with a postoperative fungal infection of the left eye. A dark-pigmented yeast, Exophiala dermatitidis (previously known as Wangiella dermatitidis), was identified from the culture of the biopsy taken from the posterior capsule. The infection was successfully eradicated by a combination of surgical and medical (i.e., voriconazole and fluconazole) treatment. This is the first report of successfully treated E. dermatitidis endophthalmitis, which demonstrates that a prompt and aggressive antifungal therapy combined with surgical intervention is necessary to prevent vision loss in cases of endophthalmitis due to Exophiala species. Beside the case description, we also aim to provide a literature review of previously reported eye infections caused by Exophiala species in order to help the future diagnosis and management of the disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11046-017-0235-4DOI Listing
June 2018

Development of a plasmid free CRISPR-Cas9 system for the genetic modification of Mucor circinelloides.

Sci Rep 2017 12 1;7(1):16800. Epub 2017 Dec 1.

MTA-SZTE Fungal Pathogenicity Mechanisms Research Group, Hungarian Academy of Sciences - University of Szeged, Közép fasor 52, H-6726, Szeged, Hungary.

Mucor circinelloides and other members of Mucorales are filamentous fungi, widely used as model organisms in basic and applied studies. Although genetic manipulation methods have been described for some Mucoral fungi, construction of stable integrative transformants by homologous recombination has remained a great challenge in these organisms. In the present study, a plasmid free CRISPR-Cas9 system was firstly developed for the genetic modification of a Mucoral fungus. The described method offers a rapid but robust tool to obtain mitotically stable mutants of M. circinelloides via targeted integration of the desired DNA. It does not require plasmid construction and its expression in the recipient organism. Instead, it involves the direct introduction of the guide RNA and the Cas9 enzyme and, in case of homology directed repair (HDR), the template DNA into the recipient strain. Efficiency of the method for non-homologous end joining (NHEJ) and HDR was tested by disrupting two different genes, i.e. carB encoding phytoene dehydrogenase and hmgR2 encoding 3-hydroxy-3-methylglutaryl-CoA reductase, of M. circinelloides. Both NHEJ and HDR resulted in stable gene disruption mutants. While NHEJ caused extensive deletions upstream from the protospacer adjacent motif, HDR assured the integration of the deletion cassette at the targeted site.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-017-17118-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5711797PMC
December 2017

The genus Parasola: phylogeny and the description of three new species.

Mycologia 2017 Jul-Aug;109(4):620-629. Epub 2017 Nov 15.

g Synthetic and Systems Biology Unit , Institute of Biochemistry , BRC, HAS, Temesvári körút 62, H-6726 Szeged , Hungary.

Parasola represents an enigmatic lineage of veil-less, coprinoid fungi in Psathyrellaceae (Agaricales). The species-level taxonomy of the genus has been in a flux recently, resulting in the elimination of some long-established names and the description of new taxa. Here, we reconstruct the phylogeny of Parasola using two nuc rDNA loci, the internal transcribed spacer region (ITS1-5.8S-ITS2) and 28S and identify several putatively undescribed species, of which three are formally described here (Parasola crataegi, P. ochracea, and P. plicatilis-similis) based on molecular and morphological data. Morphological descriptions for the new species and an identification key to accepted Parasola species are given. We revise and discuss our current understanding of the phylogeny of Parasola.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/00275514.2017.1386526DOI Listing
November 2018

Interaction of THP-1 Monocytes with Conidia and Hyphae of Different Strains.

Front Immunol 2017 18;8:1369. Epub 2017 Oct 18.

MTA-SZTE Fungal Pathogenicity Mechanisms Research Group, Hungarian Academy of Sciences, University of Szeged, Szeged, Hungary.

Interaction of the human monocytic cell line, THP-1 with clinical isolates of three species were examined. Members of this filamentous fungal genus can cause deep mycoses emerging in both immunocompromised and immunocompetent patients. It was found that monocytes reacted only to the hyphal form of . Cells attached to the germ tubes and hyphae and production of elevated levels of interleukin (IL)-8 and IL-10 and a low level of TNF-α were measured. At the same time, monocytes failed to produce IL-6. This monocytic response, especially with the induction of the anti-inflammatory IL-10, correlates well to the observation that frequently cause chronic infections even in immunocompetent persons. Despite the attachment to the hyphae, monocytes could not reduce the viability of the fungus and the significant decrease in the relative transcript level of HLA-DRA assumes the lack of antigen presentation of the fungus by this cell type. and failed to induce the gathering of the cells or the production of any analyzed cytokines. Monocytes did not recognize conidia of species, even when melanin was lacking in their cell wall.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2017.01369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5651265PMC
October 2017

Recurrent Scedosporium apiospermum mycetoma successfully treated by surgical excision and terbinafine treatment: a case report and review of the literature.

Ann Clin Microbiol Antimicrob 2017 Apr 14;16(1):31. Epub 2017 Apr 14.

MTA-SZTE "Lendület" Fungal Pathogenicity Mechanisms Research Group, Hungarian Academy of Sciences, University of Szeged, Közép fasor 52, Szeged, 6726, Hungary.

Background: Scedosporium apiospermum is an emerging opportunistic filamentous fungus, which is notorious for its high levels of antifungal-resistance. It is able to cause localized cutaneous or subcutaneous infections in both immunocompromised and immunocompetent persons, pulmonary infections in patients with predisposing pulmonary diseases and invasive mycoses in immunocompromised patients. Subcutaneous infections caused by this fungus frequently show chronic mycetomatous manifestation.

Case Report: We report the case of a 70-year-old immunocompromised man, who developed a fungal mycetomatous infection on his right leg. There was no history of trauma; the aetiological agent was identified by microscopic examination and ITS sequencing. This is the second reported case of S. apiospermum subcutaneous infections in Hungary, which was successfully treated by surgical excision and terbinafine treatment. After 7 months, the patient remained asymptomatic. Considering the antifungal susceptibility and increasing incidence of the fungus, Scedosporium related subcutaneous infections reported in the past quarter of century in European countries were also reviewed.

Conclusions: Corticosteroid treatment represents a serious risk factor of S. apiospermum infections, especially if the patient get in touch with manure-enriched or polluted soil or water. Such infections have emerged several times in European countries in the past decades. The presented data suggest that besides the commonly applied voriconazole, terbinafine may be an alternative for the therapy of mycetomatous Scedosporium infections.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12941-017-0195-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5391591PMC
April 2017

Biotransformation of copper oxide nanoparticles by the pathogenic fungus Botrytis cinerea.

Chemosphere 2017 Aug 7;180:178-185. Epub 2017 Apr 7.

Department of Biology, Biotechnical Faculty, University of Ljubljana, Jamnikarjeva 101, Ljubljana, Slovenia; Jožef Stefan Institute, Jamova cesta 39, Ljubljana, Slovenia. Electronic address:

Two plant pathogenic fungi, Botrytis cinerea and Alternaria alternata, isolated from crop plants, were exposed to Cu in ionic (Cu), microparticulate (MP, CuO) or nanoparticulate (NP, Cu or CuO) form, in solid and liquid culturing media in order to test fungal response and toxic effects of the mentioned compounds for the potential use as fungicides. B. cinerea has shown pronounced growth and lower levels of lipid peroxidation compared to A. alternata. Its higher resistance/tolerance is attributed mainly to biotransformation of CuO and Cu NPs and CuO MPs into a blue compound at the fungal/culturing media interface, recognized by Cu K-edge EXAFS analysis as Cu-oxalate complex. The pronounced activity of catechol-type siderophores and organic acid secretion in B. cinerea induce leaching and mobilization of Cu ions from the particles and their further complexation with extracellularly secreted oxalic acid. The ability of pathogenic fungus to biotransform CuO MPs and NPs hampers their use as fungicides. However the results show that B. cinerea has a potential to be used in degradation of Cu(O) nanoparticles in environment, copper extraction and purification techniques.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.chemosphere.2017.04.022DOI Listing
August 2017

Involvement of adenosine A3 receptors in the chemotactic navigation of macrophages towards apoptotic cells.

Immunol Lett 2017 03 8;183:62-72. Epub 2017 Feb 8.

Dental Biochemistry Section, Department of Biochemistry and Molecular Biology, Faculty of Dentistry, Research Center of Molecular Medicine, Hungary. Electronic address:

The first step in the clearance of apoptotic cells is chemotactic migration of macrophages towards the apoptotic cells guided by find-me signals provided by the dying cells. Upon sensing the chemotactic signals, macrophages release ATP. ATP is then degraded to ADP, AMP and adenosine to trigger purinergic receptors concentrated at the leading edge of the cell. Previous studies have shown that in addition to the chemotactic signals, this purinergic autocrine signaling is required to amplify and translate chemotactic signals into directional motility. In the present study the involvement of adenosine A receptors (A3R) was studied in the chemotactic migration of macrophages directed by apoptotic thymocyte-derived find-me signals. By taking video images in vitro, we demonstrate 1, by administering apyrase, which degrades ATP and ADP, that the purinergic autocrine signaling is required for maintaining both the velocity and the directionality of macrophage migration towards the apoptotic thymocytes; 2, by readding 5'-N-ethylcarboxamidoadenosine, an adenosine analogue, to apyrase treated cells that the adenosine receptor signaling alone is sufficient to act so; and 3, by studying migration of various adenosine receptor null or adenosine receptor antagonist-treated macrophages, that the individual loss of the A3R signaling leads to the loss of chemotactic navigation. Though loss of A3Rs does not affect the phagocytotic capacity of macrophages, intraperitoneally-injected apoptotic thymocytes were cleared with a delayed kinetics by A3R null macrophages in vivo due to the impaired chemotactic navigation. All together these data demonstrate the involvement of macrophage A3Rs in the proper chemotactic navigation and consequent in vivo clearance of apoptotic cells. Interestingly, loss of A3Rs did not affect the in vivo clearance of apoptotic thymocytes in the dexamethasone-treated thymus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.imlet.2017.02.002DOI Listing
March 2017

Purification and Properties of Extracellular Lipases with Transesterification Activity and 1,3-Regioselectivity from and .

J Microbiol Biotechnol 2017 Feb;27(2):277-288

Department of Microbiology, Faculty of Science and Informatics, University of Szeged, H-6726 Szeged, Közép fasor 52, Hungary.

NRRL 5282 and NRRL 1526 can produce lipases with high synthetic activities in wheat bran-based solid-state culture. In this study, the purification and biochemical characterization of the lipolytic activities of these lipases are presented. SDS-PAGE indicated a molecular mass of about 55 and 35 kDa for the purified and enzymes, respectively. -Nitrophenyl palmitate (NPP) hydrolysis was maximal at 40°C and pH 7.0 for the lipase, and at 30°C and pH 5.2 for the enzyme. The enzymes showed almost equal affinity to NPP, but the of the lipase was about 1.13 times higher than that determined for using the same substrate. For both enzymes, a dramatic loss of activity was observed in the presence of 5 mM Hg, Zn, or Mn, 10 mM -bromosuccinimide or sodium dodecyl sulfate, and 5-10% (v/v) of hexanol or butanol. At the same time, they proved to be extraordinarily stable in the presence of -hexane, cyclohexane, -heptane, and isooctane. Moreover, isopentanol up to 10% (v/v) and propionic acid in 1 mM concentrations increased the NPP hydrolyzing activity of lipase. Both enzymes had 1,3-regioselectivity, and efficiently hydrolyzed -nitrophenyl (NP) esters with C8-C16 acids, exhibiting maximum activity towards NP-caprylate () and pNP-dodecanoate (). The purified lipases are promising candidates for various biotechnological applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4014/jmb.1608.08005DOI Listing
February 2017

In vitro susceptibility of Scedosporium isolates to N-acetyl-L-cysteine alone and in combination with conventional antifungal agents.

Med Mycol 2016 Oct 3;54(7):776-9. Epub 2016 May 3.

University of Szeged, Faculty of Science and Informatics, Department of Microbiology, Közép fasor 52, H-6726 Szeged, Hungary.

In recent years, Scedosporium species have been more commonly recognized from severe, difficult-to-treat human infections, such as upper respiratory tract and pulmonary infections. To select an appropriate therapeutic approach for these infections is challenging, because of the commonly observed resistance of the causative agents to several antifungal drugs. Therefore, to find a novel strategy for the treatment of pulmonary Scedosporium infections the in vitro antifungal effect of a mucolytic agent, N-acetyl-L-cysteine and its in vitro combinations with conventional antifungals were investigated. Synergistic and indifferent interactions were registered in 23 and 13 cases, respectively. Antagonism was not revealed between the compounds.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/mmy/myw029DOI Listing
October 2016

Modification of tooth development by heat shock protein 60.

Int J Oral Sci 2016 Mar 30;8(1):24-31. Epub 2016 Mar 30.

Department of Oral Anatomy, Faculty of Dentistry, University of Debrecen, Debrecen, Hungary.

Although several heat shock proteins have been investigated in relation to tooth development, no available information is available about the spatial and temporal expression pattern of heat shock protein 60 (Hsp 60). To characterize Hsp 60 expression in the structures of the developing tooth germ, we used Western blotting, immunohistochemistry and in situ hybridization. Hsp 60 was present in high amounts in the inner and outer enamel epithelia, enamel knot (EK) and stratum intermedium (SI). Hsp 60 also appeared in odontoblasts beginning in the bell stage. To obtain data on the possible effect of Hsp 60 on isolated lower incisors from mice, we performed in vitro culturing. To investigate the effect of exogenous Hsp 60 on the cell cycle during culturing, we used the 5-bromo-2-deoxyuridine (BrdU) incorporation test on dental cells. Exogenously administered Hsp 60 caused bluntness at the apical part of the 16.5-day-old tooth germs, but it did not influence the proliferation rate of dental cells. We identified the expression of Hsp 60 in the developing tooth germ, which was present in high concentrations in the inner and outer enamel epithelia, EK, SI and odontoblasts. High concentration of exogenous Hsp 60 can cause abnormal morphology of the tooth germ, but it did not influence the proliferation rate of the dental cells. Our results suggest that increased levels of Hsp 60 may cause abnormalities in the morphological development of the tooth germ and support the data on the significance of Hsp during the developmental processes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/ijos.2015.53DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4822183PMC
March 2016
-->