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PubMed2003

Genomic sequence of a ranavirus (family Iridoviridae) associated with salamander mortalities in North America.

Disease is among the suspected causes of amphibian population declines, and an iridovirus and a chytrid fungus are the primary pathogens associated with amphibian mortalities. Ambystoma tigrinum virus (ATV) and a closely related strain, Regina ranavirus (RRV), are implicated in salamander die-offs in Arizona and Canada, respectively. We report the complete sequence of the ATV genome and partial sequence of the RRV genome. Sequence analysis of the ATV/RRV genomes showed marked similarity to other ranaviruses, including tiger frog virus (TFV) and frog virus 3 (FV3), the type virus of the genus Ranavirus (family Iridoviridae), as well as more distant relationships to lymphocystis disease virus, Chilo iridescent virus, and infectious spleen and kidney necrosis virus. Putative open reading frames (ORFs) in the ATV sequence identified 24 genes that appear to control virus replication and block antiviral responses. In addition, >50 other putative genes, homologous to ORFs in other iridoviral genomes but of unknown function, were also identified. Sequence comparison performed by dot plot analysis between ATV and itself revealed a conserved 14-bp palindromic repeat within most intragenic regions. Dot plot analysis of ATV vs RRV sequences identified several polymorphisms between the two isolates. Finally, a comparison of ATV and TFV genomic sequences identified genomic rearrangements consistent with the high recombination frequency of iridoviruses. Given the adverse effects that ranavirus infections have on amphibian and fish populations, ATV/RRV sequence information will allow the design of better diagnostic probes for identifying ranavirus infections and extend our understanding of molecular events in ranavirus-infected cells.

Animals↗
PubMed2002

The plant disease resistance gene Asc-1 prevents disruption of sphingolipid metabolism during AAL-toxin-induced programmed cell death.

The nectrotrophic fungus Alternaria alternata f.sp. lycopersici infects tomato plants of the genotype asc/asc by utilizing a host-selective toxin, AAL-toxin, that kills the host cells by inducing programmed cell death. Asc-1 is homologous to genes found in most eukaryotes from yeast to humans, suggesting a conserved function. A yeast strain with deletions in the homologous genes LAG1 and LAC1 was functionally complemented by Asc-1, indicating that Asc-1 functions in an analogous manner to the yeast homologues. Examination of the yeast sphingolipids, which are almost absent in the lag1Deltalac1Delta mutant, showed that Asc-1 was able to restore the synthesis of sphingolipids. We therefore examined the biosynthesis of sphingolipids in tomato by labeling leaf discs with l-[3-3H]serine. In the absence of AAL-toxin, there was no detectable difference in sphingolipid labeling between leaf discs from Asc/Asc or asc/asc leaves. In the presence of pathologically significant concentrations of AAL-toxin however, asc/asc leaf discs showed severely reduced labeling of sphingolipids and increased label in dihydrosphingosine (DHS) and 3-ketodihydrosphingosine (3-KDHS). Leaf discs from Asc/Asc leaves responded to AAL-toxin treatment by incorporating label into different sphingolipid species. The effects of AAL-toxin on asc/asc leaflets could be partially blocked by the simultaneous application of AAL-toxin and myriocin. Leaf discs simultaneously treated with AAL-toxin and myriocin showed no incorporation of label into sphingolipids or long-chain bases as expected. These results indicate that the presence of Asc-1 is able to relieve an AAL-toxin-induced block on sphingolipid synthesis that would otherwise lead to programmed cell death.

Alternaria↗
PubMed1987

Bronchial asthma. Mechanisms and management of a complex obstructive airway disease.

Airway hyperreactivity to physical, chemical, and pharmacologic stimuli is a hallmark of bronchial asthma. In patients with extrinsic (allergic) asthma, in whom an immunologic mechanism of the IgE type can be demonstrated, specific sensitivity develops to a variety of common environmental substances, including pollen, fungus spores, house dust mites, and animal danders. Persons with intrinsic asthma, in whom immunologic mechanisms are hard to demonstrate, often have chronic sinus disease and nasal polyps and manifest clinical intolerance to nonsteroidal antiinflammatory agents. Evaluation of asthma includes a history and complete physical examination, skin tests, radioallergosorbent tests, pulmonary function tests, blood gas determination, and inhalation challenge tests. Treatment is focused on environmental control, pharmacotherapy, and immunotherapy.

Adrenal Cortex Hormones↗
PubMedDate not supplied

Pulmonary coccidioidal mycetoma.

Cavitary pulmonary disease due to coccidioidomycosis is common; however, development of both the underlying cavity and the fungus ball due to Coccidioides immitis is rare and has been reported on only five occasions. We report a case of coccidioidal mycetoma formation as a late sequelae of primary pulmonary coccidioidal pneumonia. Therapy with 2 gm of amphotericin B was unsuccessful and, because of recurrent hemoptysis, the patient required lobar resection. Endosporulating spherules, as well as septate mycelia with arthrospore formation, were found on histologic examination. The medical and surgical management, as well as the potential of such lesions to produce human to human transmission, is discussed.

Coccidioides↗
PubMed2004

Chytridiomycosis impacts predator-prey interactions in larval amphibian communities.

Despite ecologists increasingly recognizing pathogens as playing significant roles in community dynamics, few experimental studies have quantified patterns of disease impacts on natural systems. Amphibians are experiencing population declines, and a fungal pathogen ( Batrachochytrium dendrobatidis; Chytridiomycota) is a suspected causal agent in many declines. We studied the effects of a pathogenic fungus on community interactions between the gray treefrog, Hyla chrysoscelis, and eastern newts, Notophthalmus viridescens. Recent studies have characterized chytridiomycosis as an emerging infectious disease, whose suspected rapid range expansion and widespread occurrence pose a significant risk for amphibian populations worldwide. We reared larvae in outdoor polyethylene experimental tanks and tested the effects of initial larval density, predator presence, and fungal exposure on Hyla recruitment and predator-prey interactions between Hyla and Notophthalmus. Newts reduced treefrog survival, and high intraspecific density decreased metamorphic body mass independent of B. dendrobatidis. The presence of fungi reduced treefrog body mass at metamorphosis by 34%, but had no significant main effect on survival or larval period length. B. dendrobatidis differentially affected larval development in the presence of predators; Hyla developed slower when reared with the pathogen, but only when newts were present. This significant predator-by-pathogen interaction suggests that the impact of chytridiomycosis on larval amphibians may be exacerbated in complex communities. Our data suggest that B. dendrobatidis effects on host life history may be complex and indirect. Direct measurements of the community-level effects of pathogens offer an important opportunity to understand a significant threat to global biodiversity-declining amphibian populations.

Analysis of Variance↗
PubMed2005

Pithomycotoxicosis (facial eczema) in ruminants in the Azores, Portugal.

Outbreaks of pithomycotoxicosis (facial eczema), a hepatogenous photosensitisation caused by the mycotoxin sporidesmin, have affected ruminants in the Azores Islands of Portugal after warm, humid periods during late summer and autumn. Twenty-two outbreaks were recorded in cattle between 1999 and 2001, affecting 11.4 per cent of the animals in the affected herds, and in 2000 there was an outbreak in one sheep flock in which more than 20 per cent of the sheep died. The clinical signs included decreases in milk production, weight loss, photosensitisation and its sequelae, including death. The animals had high activities of gamma glutamyltransferase in their serum, and icterus and severe liver disease, including biliary hyperplasia and fibrosis, were found postmortem. The characteristic spores of the toxigenic saprophytic fungus Pithomyces chartarum were found on grass; all 381 isolates of the fungus were toxigenic for sporidesmin by elisa, and the results were confirmed by high-performance liquid chromatography analysis. Cattle from farms at greatest risk of pithomycotoxicosis were protected by supplementing their concentrate feed with zinc oxide, or using a slow-release intraruminal zinc bolus.

Animals↗
PubMed2001

Leptosphaeria maculans, the causal agent of blackleg disease of Brassicas.

The loculoascomycete Leptosphaeria maculans (anamorph: Phoma lingam) causes blackleg of Brassicas, including Brassica napus (canola or rapeseed). This fungus probably comprises several morphologically similar species; taxonomic relationships between them are being clarified and nomenclature is being revised. The pathotype ("A" group) responsible for major economic losses to canola has been studied in more detail than other members of this species complex and is the focus of this review. L. maculans is haploid, outcrossing, can be transformed, and has a genome size of about 34 Mb. Preliminary genetic and physical maps have been developed and three genes involved in host specificity have been mapped. As yet, few genes have been characterized. Chemical analysis of fungal secondary metabolites has aided understanding of taxonomic relationships and of the host-fungal interaction by the unraveling of pathways for detoxification of antimicrobial phytoalexins. Several phytotoxins (host and nonhost specific) have been identified and a complex pattern of regulation of their synthesis by fungal and host metabolites has been discovered.

Ascomycota↗
PubMedDate not supplied

[Histopathological study on the course of a dermatophytic disease].

Histological study of cutaneous biopsies of an algerian girl with a "dermatophytic disease" (cf. supra Marill and al.). During the six first years of evolution diagnosis of mycosis had not been made for no specific fungus staining was done, but the fungus was present in the tissues. Vesicular forms and few filaments were seen in the first biopsies but polymorphism increased with the time and filaments became predominant and very abundant at the end of the disease.

Adolescent↗
PubMed2002

Deoxynivalenol-nonproducing fusarium graminearum causes initial infection, but does not cause disease spread in wheat spikes.

Fusarium graminearum is a major pathogen that causes fusarium head blight (FHB) in wheat and produces deoxynivalenol (DON) in infected grain. In previous studies, the trichodiene synthase gene (Tri5) in the fungal strain GZ3639 was disrupted to produce the DON-nonproducing strain GZT40. In this report, the virulence of strains GZ3639 and GZT40 was tested on wheat cultivars with various resistance levels by using methods of spray inoculation and injection inoculation with fungal conidia. Under field and greenhouse conditions, strain GZ3639 produced significantly more disease symptoms and reduced more yield than strain GZT40 in all wheat cultivars tested. Conidia of strain GZT40 germinated and infected inoculated spikelets, but disease symptoms were limited to inoculated spikelets without spread to uninoculated spikelets. When strain GZT40 was inoculated using the spray method, multiple initial infection sites in a spike resulted in higher levels of disease symptoms than in spikes inoculated by a single injection. Greenhouse tests confirmed that strain GZT40 did not produce DON in the infected kernels following either inoculation method. The results confirm that DON production plays a significant role in the spread of FHB within a spike, and are the first report that DON production is not necessary for initial infection by the fungus.

Fusarium↗
PubMed1993

Alteration of tissue and serum sphinganine to sphingosine ratio: an early biomarker of exposure to fumonisin-containing feeds in pigs.

Fumonisins are a group of naturally occurring compounds produced by the fungus Fusarium moniliforme. They are believed to be the etiologic agent of several animal diseases associated with consumption of corn-based feeds including porcine pulmonary edema. Recently it was shown in vitro that fumonisins are specific inhibitors of sphingosine and sphinganine N-acyltransferases. Inhibition of these enzymes in cultured cells results in the accumulation of free long chain sphingoid bases, specifically sphingosine and sphinganine, and the depletion of complex sphingolipids. In this study, tissues and serum from male SPF pigs fed a nutritionally balanced diet containing corn or corn screenings naturally contaminated with fumonisins for up to 14 days were analyzed for free sphingoid bases and complex sphingolipids. Total fumonisins (B1 and B2) in the diets were analyzed at 0 (< 1), 5, 23, 39, 101, and 175 ppm. Pulmonary edema only occurred at 175 ppm, while histologic liver damage was present at > or = 23 ppm, and serum liver enzymes were significantly elevated at > or = 101 ppm. The results of this study show that free sphinganine is elevated in liver, lung, and kidney, from pigs consuming feeds containing fumonisins at total fumonisin concentrations of 23 ppm or greater. Sphingosine is also elevated in a dose-dependent manner, but to a lesser extent than sphinganine. The consequence of this differential inhibition is that the ratio of sphinganine to sphingosine increases, suggesting that sphinganine N-acyltransferase is the preferred target for fumonisins. Elevation of free sphinganine and free sphingosine in serum paralleled the increases in tissues. Statistically significant increases in the ratio were observed at feed concentrations as low as 5 ppm total fumonisins and in pigs (at higher concentrations) in which other serum biochemistry parameters and tissue morphology were not altered. Elevated ratios were also observed in serum from pigs fed pure fumonisin B1. The sensitivity of the ratio indicates that it could serve as an effective biomarker for consumption of fumonisin-containing feeds. In addition, the data supports the hypothesis that inhibition of sphingosine and sphinganine N-acyltransferase plays an important role in the pathogenesis of animal diseases associated with consumption of feed containing fumonisins.

Animal Feed↗
PubMed2004

Physiology and molecular characteristics of a pine wilt nematode-trapping fungus, Monacrosporium megalosporum.

We isolated the nematode-trapping fungus Monacrosporium megalosporum from nature and examined its morphology, physiology and molecular characteristics. The nematode-trapping device of this fungus is a three-dimensional network. This fungus captures the pine wilt nematode (Bursaphelenchus xylophilus), but not a non-phytopathogenic nematode that is morphologically similar to B. xylophilus. The phylogenic relationship of the nucleotide sequence of the rDNA ITS region was close to those of M. thaumasium and Geniculifera eudermata, which also have nematode-trapping devices that are three-dimensional networks. Acidic pH inhibited both the liberation and regeneration of protoplasts. Moreover, cytoplasmic granulation of protoplasts was found below pH 6.0. Mycelial growth on agar media was also inhibited below pH 4, but not at pH 9. These results strongly suggest that the activity of this fungus is inhibited by acid rain in the field. Therefore, development of pine wilt disease might be a secondary effect of acid rain.

Animals↗
PubMed2003

Analysis of the structure and inheritance of a linear plasmid from the obligate biotrophic fungus Blumeria graminis f. sp. hordei.

A linear plasmid is widespread among isolates of the obligate biotrophic fungus Blumeria graminis f.sp. hordei (synonym Erysiphe graminis) (Bgh), the organism that causes the disease powdery mildew on barley. We cloned and sequenced the entire plasmid of 7965 bp. The plasmid contains two identical terminal inverted repeats (TIR) of 610 bp. Two ORFs are present on opposite strands, one encoding a phage-type DNA polymerase and the other a phage-type RNA polymerase. Two large transcripts of approximately 4.2 and 5.6 kb were identified in conidia, germinating conidia and Bgh -infected barley leaves, indicating that the polymerases are transcribed at most stages of the lifecycle. The transcription start sites were localised within the TIR regions, where a putative 11-bp ARS consensus sequence was also identified. To follow the sexual transmission of the plasmid we screened 27 Bgh isolates for mitochondrial polymorphisms. One polymorphism allowed us to carry out a cross between two isolates that differed in both mitochondrial genotype and presence/absence of the Bgh plasmid. The plasmid was transmitted independently of the origin of the mitochondria. No transfer of the plasmid was observed between two Bgh isolates that were co-cultivated for 1.5 years on a common susceptible barley variety. The plasmid appears to be an autonomous replicon with no phenotypic effect on Bgh.

Ascomycota↗
PubMed1998

A role for jasmonate in pathogen defense of Arabidopsis.

To investigate the role of jasmonate in the defense of plants against fungal pathogens, we have studied a mutant of Arabidopsis, fad3-2 fad7-2 fad8, that cannot accumulate jasmonate. Mutant plants were extremely susceptible to root rot caused by the fungal root pathogen Pythium mastophorum (Drechs.), even though neighboring wild-type plants were largely unaffected by this fungus. Application of exogenous methyl jasmonate substantially protected mutant plants, reducing the incidence of disease to a level close to that of wild-type controls. A similar treatment with methyl jasmonate did not protect the jasmonate-insensitive mutant coi1 from infection, showing that protective action of applied jasmonate against P. mastophorum was mediated by the induction of plant defense mechanisms rather than by a direct antifungal action. Transcripts of three jasmonate-responsive defense genes are induced by Pythium challenge in the wild-type but not in the jasmonate-deficient mutant. Pythium species are ubiquitous in soil and root habitats world-wide, but most (including P. mastophorum) are considered to be minor pathogens. Our results indicate that jasmonate is essential for plant defense against Pythium and, because of the high exposure of plant roots to Pythium inoculum in soil, may well be fundamental to survival of plants in nature. Our results further indicate that the fad3-2 fad7-2 fad8 mutant is an appropriate genetic model for studying the role of this important signaling molecule in pathogen defense.

Journal Article↗
PubMed1999

In vitro and in vivo anticandidal activity of human immunodeficiency virus protease inhibitors.

Highly active antiretroviral therapy that includes human immunodeficiency virus (HIV) aspartyl protease inhibitors (PIs) causes a decline in the incidence of some opportunistic infections in AIDS, and this decline is currently attributed to the restoration of specific immunity. The effect of two PIs (indinavir and ritonavir) on the enzymatic activity of a secretory aspartyl protease (Sap) of Candida albicans (a major agent of mucosal disease in HIV-infected subjects) and on growth and experimental pathogenicity of this fungus was evaluated. Both PIs strongly (>/=90%) and dose dependently (0.1-10 microM) inhibited Sap activity and production. They also significantly reduced Candida growth in a nitrogen-limited, Sap expression-dependent growth medium and exerted a therapeutic effect in an experimental model of vaginal candidiasis, with an efficacy comparable to that of fluconazole. Thus, besides the expected immunorestoration, patients receiving PI therapy may benefit from a direct anticandidal activity of these drugs.

AIDS-Related Opportunistic Infections↗
PubMedDate not supplied

Therapeutic evaluation of ketoconazole in patients with coccidioidomycosis.

Eleven adult patients (seven men and four nonpregnant women) with coccidioidomycosis were treated orally with ketoconazole (R41,400). Two patients presented with disseminated coccidioidomycosis, six with pulmonary coccidioidomycosis, and three with the chronic cutaneous form of the disease. Diagnosis was established by culture of Coccidioides immitis and/or histopathologic identification of the fungus. All patients received 400 mg of ketoconazole per day for the first 10 days; afterwards four of them received 200 mg per day. Evaluation indicated that nine patients improved, one did not, and one could not be assessed. Treatment of coccidioidomycosis with ketoconazole appears to be reasonably effective and produces fewer adverse effects than does amphotericin B; however, further studies of the efficacy of this new drug are needed.

Adult↗
PubMed2002

Characterization of glucosylceramides in Pseudallescheria boydii and their involvement in fungal differentiation.

Pseudallescheria boydii is a fungal pathogen that causes disease in immunocompromised patients. Ceramide monohexosides (CMHs) were purified from lipidic extracts of this fungus, showing that, as described for several other species, P. boydii synthesizes glucosylceramides as major neutral glycosphingolipids. CMHs from P. boydii were analyzed by high-performance thin-layer chromatography, gas chromatography coupled to mass spectrometry, fast atom bombardment-mass spectrometry, and nuclear magnetic resonance. These combination of techniques allowed the identification of CMHs from P. boydii as molecules containing a glucose residue attached to 9-methyl-4,8-sphingadienine in amidic linkage to 2-hydroxyoctadecanoic or 2-hydroxyhexadecanoic acids. Antibodies from a rabbit infected with P. boydii recognized CMHs from this fungus. Antibodies to CMH were purified from serum and used in indirect immunofluorescence, which revealed that CMHs are detectable on the surface of mycelial and pseudohyphal but not conidial forms of P. boydii, suggesting a differential expression of glucosylceramides according with morphological phase. We also investigated the influence of antibodies to CMH on growth and germ tube formation in P. boydii. Cultures that were supplemented with these antibodies failed to form mycelium, but the latter was not affected once formed. Similar experiments were performed to evaluate whether antibodies to CMH would influence germ tube formation in Candida albicans, a fungal pathogen that synthesizes glucosylceramide and uses differentiation as a virulence factor. Addition of antiglucosylceramide antibodies to cultures of C. albicans clearly inhibited the generation of germ tubes. These results indicated that fungal CMHs might be involved in the differentiation and, consequently, play a role on the infectivity of fungal cells.

Cell Differentiation↗
PubMed2006

Primary cutaneous coccidiodomycosis: case report and review of the literature.

BACKGROUND: Coccidiodomycosis is a systemic infection caused by Coccidioides immitis, a dimorphic fungus endemic in the south of the USA and the north of Mexico. The disease usually affects the lungs. Primary cutaneous infection is extremely rare. We present a report of a patient with primary cutaneous infection located on the nose. To our knowledge, such a presentation has never previously been reported in the literature. OBSERVATIONS: The patient had a 3-cm-diameter elevated nodule with a verrucous aspect located on the tip of her nose. The histopathologic features of the lesion were consistent with coccidioidomycosis. CONCLUSIONS: To our knowledge, this is the first report of primary cutaneous coccidioidomycosis located on the tip of nose.

Adult↗