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PubMed2006

Expression of antibodies directed to Paracoccidioides brasiliensis glycosphingolipids during the course of paracoccidioidomycosis treatment.

Paracoccidioidomycosis (PCM) is a granulomatous disease caused by the dimorphic fungus Paracoccidioides brasiliensis. The immunoglobulin classes and isotypes of antibodies directed to acidic glycosphingolipids (GSLs) and glucosylceramide of P. brasiliensis were determined by enzyme-linked immunosorbent assay of sera from 31 PCM patients. The reactivities of 38 serum samples were analyzed by considering the stage of treatment: before antifungal treatment (n = 10), during 1 to 4 months of treatment (T1-4; n = 9), during 5 to 12 months of treatment (T5-12; n = 9), and posttreatment (PT; n = 10). Sera from healthy subjects (n = 12) were used as controls. Only the GSL Pb-1 antigen, which presents the carbohydrate structure Galfbeta1-6(Manalpha1-3)Manbeta1, was reactive with the PCM patient sera. The PCM patient sera did not react with Pb-2, which lacks the Galf residue and which is considered the biosynthetic precursor of Pb-1, indicating that the Galf residue is essential for antibody reactivity. The Pb-1 glycolipid from nontreated patients elicited a primary immune response with immunoglobulin M (IgM) production and subsequent switching to IgG1 production. The IgG1 titer increased after the start of antifungal treatment (T1-4 group), and general decreases in the anti-Pb-1 antibody titers were observed after 5 months of treatment (T5-12 and PT groups). The Pb-1 antigen, an acidic GSL with terminal Galf residue, has potential application as an elicitor of the host immune response in patients with PCM.

Adult↗
PubMed2002

Uptake of Aspergillus fumigatus Conidia by phagocytic and nonphagocytic cells in vitro: quantitation using strains expressing green fluorescent protein.

Several pathogenic fungal organisms enter eukaryotic cells and manipulate the host cell environment to favor their own growth and survival. Aspergillus fumigatus is a saprophytic fungus that causes invasive lung disease in the immunocompromised host. To determine whether A. fumigatus could enter eukaryotic cells, we studied the uptake of two different GFP-expressing A. fumigatus strains into A549 lung epithelial cells, human umbilical vein endothelial (HUVE) cells, and J774 murine macrophages in vitro. A549 cells internalized 30% of the bound conidia whereas HUVE and J774 cells internalized 50 and 90%, respectively. Conidia within A549 cells remained viable for 6 h; however, 60 to 80% of conidia within J774 cells were killed after only 4 h. Live and heat-killed conidia were internalized to the same extent by A549 cells. After 6 h, almost none of the conidia inside A549 cells had germinated, whereas extracellular conidia had developed germ tubes. Internalization of conidia by A549 cells was a temperature-dependent process and required rearrangement of the underlying host cell cytoskeleton; uptake was inhibited by 75% with 0.5 microM cytochalasin D and by 65% with 5 microM colchicine. Fluorescent labeling of infected A549 cells with rhodamine phalloidin provided visible evidence of cytoskeletal alteration as many of the intracellular conidia were contained in actin-coated phagosomes. These data provide evidence that significant numbers of A. fumigatus conidia can be internalized by nonprofessional phagocytes in vitro and these cells may serve as reservoirs for immune cell evasion and dissemination throughout the host.

Actin Cytoskeleton↗
PubMed2004

Gene expression in HL60 granulocytoids and human polymorphonuclear leukocytes exposed to Candida albicans.

Candida albicans is an opportunistic human pathogen causing both superficial and disseminated diseases. It is a dimorphic fungus, switching between yeast and hyphal forms, depending on cues from its microenvironment. Hyphae play an important role in the pathogenesis of candidiasis. The host's response to Candida infection is multifaceted and includes the participation of granulocytes as key effector cells. The aim of this investigation was to study host gene expression during granulocyte-Candida interaction. Effector cells were generated by the granulocytic differentiation of HL60 cells. The resulting cell population was shown to be morphologically and functionally equivalent to granulocytes and is therefore referred to as HL60 granulocytoids for the purposes of this study. Gene expression profiles were determined 1 h after hosts were infected with C. albicans. Three Candida-granulocytoid ratios were chosen to reflect different degrees of HL60 granulocytoid inhibition of C. albicans. The data demonstrate that at the high pathogen-host ratio, C. albicans modulated the HL60 granulocytoid's response by downregulating the expression of known antimicrobial genes. In addition, looking at the expression of a large number of genes, not all of which have necessarily been implicated in candidastatic or candidacidal mechanisms, it has been possible to describe the physiological response of the HL60 granulocytoid to an infectious challenge with C. albicans. Finally, some of the observed changes in HL60 granulocytoid gene expression were investigated in freshly isolated human polymorphonuclear leukocytes infected with C. albicans. Similar changes were seen in these primary human cells, lending support to the validity of this model.

Candida albicans↗
PubMed2004

Survival of Aspergillus fumigatus in serum involves removal of iron from transferrin: the role of siderophores.

Aspergillus fumigatus is a filamentous fungus which can cause invasive disease in immunocompromised individuals. A. fumigatus can grow in medium containing up to 80% human serum, despite very low concentrations of free iron. The purpose of this study was to determine the mechanism by which A. fumigatus obtains iron from the serum iron-binding protein transferrin. In iron-depleted minimal essential medium (MEM), A. fumigatus growth was supported by the addition of holotransferrin (holoTf) or FeCl(3) but not by the addition of apotransferrin (apoTf). Proteolytic degradation of transferrin by A. fumigatus occurred in MEM-serum; however, transferrin degradation did not occur until late logarithmic phase. Moreover, transferrin was not degraded by A. fumigatus incubated in MEM-holoTf. Urea polyacrylamide gel electrophoresis showed that in MEM-holoTf, holoTf was completely converted to apoTf by A. fumigatus. In human serum, all of the monoferric transferrin was converted to apoTf within 8 h. Siderophores were secreted by A. fumigatus after 8 h of growth in MEM-serum and 12 h in MEM-holoTf. The involvement of small molecules in iron acquisition was confirmed by the fact that transferrin was deferrated by A. fumigatus even when physically separated by a 12-kDa-cutoff membrane. Five siderophores were purified from A. fumigatus culture medium, and the two major siderophores were identified as triacetylfusarinine C and ferricrocin. Both triacetylfusarinine C and ferricrocin removed iron from holoTf with an affinity comparable to that of ferrichrome. These data indicate that A. fumigatus survival in human serum in vitro involves siderophore-mediated removal of iron from transferrin. Proteolytic degradation of transferrin may play a secondary role in iron acquisition.

Aspergillosis↗
PubMed1999

Experience with invasive Candida infections.

Between January and July 1995, 227 patients at the Bronx-Lebanon Hospital Center had positive fungal cultures. Candida spp were the most common fungi isolated. Forty-three patients with invasive disease, as indicated by fungus-positive blood cultures, became the focus of our study. C albicans caused fungaemia in 21 patients (49%). Twenty-eight patients (65%) were less than 50 years of age; three were neonates. The most common presenting symptoms were fever, chills, and weakness (20 patients, 47%). Thirty patients died, giving a mortality rate of 70%. The patients who died stayed in the hospital an average of 49 days. The highest mortality occurred among patients who became bacteraemic before or at the same time they became candidaemic (24 of 26 patients) or who were receiving broad-spectrum antibiotics (20 of 26 patients). We also found high mortality rates from invasive fungal infection among patients with HIV infection, a central venous catheter, and liver, renal, or respiratory failure. We did not find any increase in the incidence of invasive fungal infection or mortality among leukopenic or diabetic patients.

Adolescent↗
PubMed2005

Induction of wheat defense and stress-related genes in response to Fusarium graminearum.

Fusarium head blight (FHB), caused by species of the fungus Fusarium, is a worldwide disease of wheat (Triticum aestivum L.). The Chinese T. aestivum 'Ning7840' is one of few wheat cultivars with resistance to FHB. To identify differentially expressed genes corresponding to FHB resistance, a cDNA library was constructed using pooled mRNA isolated from glumes of 'Ning7840' harvested at 2, 6, 12, 24, 36, 72, and 96 h after inoculation (hai) with a conidia spore suspension of Fusarium graminearum. Suppressive subtractive hybridization (SSH) cDNA subtraction was carried out using pooled glume mRNAs from the tester and the control. The cDNA library was differentially screened using the forward subtracted cDNAs and the reverse subtracted cDNAs as probes. Twenty-four clones with significant matches to either plant (16 sequences) or fungal (8 sequences) genes were isolated based on their specific hybridization with forward subtracted cDNA and not reverse subtracted cDNA. Six putative defense-related genes were confirmed by real-time quantitative reverse-transcriptase PCR. Many-fold higher induction of three clones (A3F8, B10H1, and B11H3) in the resistant genotypes compared with susceptible genotypes indicates a putative role in the resistance response to Fusarium graminearum. Transcript accumulations of P450, chitinase (Chi1), and one unknown gene (clone B8Q9) in both resistant and susceptible genotypes suggest an involvement in a generalized resistance response to F. graminearum. Nucleotide sequence analysis showed that cDNA clone A4C6 encodes a cytochrome P450 gene (CYP709C3v2), including 14 N-terminal amino acids that have a membrane-associated helical motif. Other domains characteristic of eukaryotic P450 are also present in CYP709C3v2. The deduced polypeptide of cDNA clone B2H2 encodes an acidic isoform of class I chitinase containing a 960-bp coding region. Southern hybridization using aneuploid lines of T. aestivum 'Chinese Spring' indicated that CYP709C3v2 was located on the short arm of chromosomes 2B and 2D.

Amino Acid Sequence↗
PubMed2006

Isolation and properties of extracellular proteinases of Penicillium marneffei.

Penicillium marneffei is a dimorphic fungus native to Southeast Asia. Disease caused by this organism, until recently a very rare condition, has increased dramatically in parallel with the increase in the number of individuals in the region immunocompromised by AIDS and other conditions. While much research has been performed on the control of dimorphic switching in P. marneffei, there is a relative dearth of information regarding the proteinases secreted by this pathogen. Our laboratory has purified and characterized two proteinases produced by this organism in liquid culture and cloned the gene of a third. Both the recombinant enzyme expressed from the cloned gene and one of those purified from culture supernatants have been identified as members of the eqolisin family, a group of pepstatin-insensitive acid proteinases. The other enzyme purified from a culture supernatant is a serine proteinase with activity in the neutral pH range. These enzymes appear to be differentially expressed, depending on culture conditions.

Amino Acid Sequence↗
PubMed2003

Idiopathic granulomatous gastritis with multiple aphthoid ulcers.

A 47-year-old woman had idiopathic granulomatous gastritis characterized by serpiginous aphthoid ulcer with satellite aphthous ulcers at the antrum to angulus with noncaseating epithelioid granulomas including giant cells in the gastric mucosa. No definite etiologic factors could be detected; systemic sarcoidosis, Crohn's disease, infections (tuberculosis, syphilis and fungus), neoplasm, and foreign body reaction were excluded by additional investigations. However, the patient was found to be infected with H. pylori. Despite the success of H. pylori-eradication, the granulomatous lesion took a long time to heal for at least 17 months or more. The relation between granulomatous gastritis and H. pylori was discussed. There was no apparent evidence of granuloma in the other organs during clinical and follow-up studies for over three years.

Anemia, Iron-Deficiency↗
PubMedDate not supplied

Mycetoma of the foot caused by Cylindrocarpon lichenicola in an immunocompetent traveler.

Cylindrocarpon is a cosmopolitan soil fungus, which rarely causes human disease. It has infrequently been reported as causing keratitis, mycetoma, osteomyelitis and peritonitis in chronic peritoneal ambulatory dialysis patients and disseminated infection in leukemic neutropenic hosts. This report describes a case of invasive infection caused by Cylindrocarpon lichenicola, localized in the right foot of an otherwise immunocompetent traveler.

Foot Dermatoses↗
PubMed1999

[The Research Encouragement Award. Effects of sex hormones on sexual difference of experimental paracoccidioidomycosis].

Paracoccidioidomycosis is a deep mycosis in Latin America. The causative agent is Paracoccidioides brasiliensis, a thermal dimorphic fungus. The incidence of the disease is much higher in men than in women. Although one explanation is the inhibitive effect of estradiol on fungal growth, its effect on the yeast form growth of P. brasiliensis is still unclear. There is limited information on progesterone and testosterone, which shows weak or no effects. On the other hand, numerous studies on sexual differences between male and female animals have been made with experimental paracoccidioidomycosis. The conclusions however, remain unclear. The present study shows the effects of estradiol (17 beta-estradiol), progesterone and testosterone on the yeast form growth of P. brasiliensis, and the sexual difference of the susceptibility in adult BALB/c mice at the initial stages of infection with view of their estrous cycles and body weight. The inhibitive effects of estradiol, progesterone and testosterone on the yeast form growth of P. brasiliensis were examined using a brain heart infusion broth with different doses of these hormones. The inhibition by estradiol was dose-dependent within the range of physiological concentrations. While the inhibitive effect of progesterone and testosterone was very weak. The phenomenon that estradiol inhibited the yeast form growth of P. brasiliensis may be one important reason for the sexual differences of paracoccidioidomycosis. The initial stages of the yeast form cells of P. brasiliensis infection were evaluated by three inoculation routes: intravenous, intraperitoneal and intratracheal. The mice were divided into 6 groups, including male and female at proestrus, estrus, metestrus- I, metestrus- II and diestrus. Four hours after inoculation, blood samples, peritoneal lavage and pulmonary homogenates were collected and their colony forming units were examined on brain heart infusion agar plates with 1 % of dextrose and 50 mg per liter of chloramphenicol. In all inoculation routes, the clearance of the yeast cells was influenced by the estrous cycles. In particular, female mice at estrus, thought to have high blood estradiol levels, showed a marked clearance of the yeast cells from the blood, peritoneal cavity and lung. All female groups inoculated by any of the three different routes, showed much higher clearance than the male groups. These results suggest that non-specific host resistance to the yeast form cells of P. brasiliensis in females was much higher than in males. There are two explanations for the tendency of higher occurrence of paracoccidioidomycosis in men. One is the inhibitive effect of estradiol on the growth of P. brasiliensis and the other is the superior tendency of non-specific host resistance in females than in males. These two factors seem to have synergistic actions in the sexual difference of paracoccidioidomycosis.

Animals↗
PubMed2004

Transmission of Batrachochytrium dendrobatidis within and between amphibian life stages.

Chytridiomycosis is an emerging infectious disease caused by the chytrid fungus Batrachochytrium dendrobatidis, which has been implicated in amphibian declines worldwide. The mountain yellow-legged frog Rana muscosa is a declining amphibian species that can be infected by B. dendrobatidis; however, transmission between conspecifics has not been documented. Here, we present experimental evidence that R. muscosa tadpoles can be infected by fungal zoospores and that they can transmit infection to each other and to postmetamorphic animals. We compared several techniques for detecting B. dendrobatidis transmission and found that histology with serial sectioning was able to detect infection before cytology or visual inspections. We also show that R. muscosa tadpoles appear healthy with B. dendrobatidis infection, while postmetamorphic animals experience mortality. In addition, we provide guidelines for visually detecting B. dendrobatidis in R. muscosa tadpoles, which may be useful in other affected species. Field surveys of infected and uninfected populations verify this identification technique.

Animals↗
PubMed1995

Candida albicans, the opportunist. A cellular and molecular perspective.

Candida albicans causes the majority of opportunistic fungal infections. The yeast's commensualistic relationship with humans enables it, when environmental conditions are favorable, to multiply and replace much of the normal flora. Virulence factors of C. albicans, enabling the organism to adhere to and penetrate host tissues, involve specific molecular interactions between the cells of the fungus and the host. Localized disease, such as oral candidiasis, onychomycosis, and vaginitis, results. These infections are usually limited to surfaces of the host, and can be quickly and successfully controlled by the use of one of the available antifungal agents. Candida albicans infections typically become systemic and life threatening when the host is immunocompromised. Depending on the immune defect in the host, one of the spectrum of Candida diseases can develop. If successful treatment of these patients is to be achieved, modulation of the immune deficit, as well as the use of an appropriate antifungal drug, must become a routine part of therapeutic interventions.

Antifungal Agents↗
PubMed1979

[Particular features of mycotic carriers (author's transl)].

Although we are all carriers of fungi, an infection is rare. Therefore, the following questions are discussed: Why do these actually saprophytic germs become pathogenic at all? Why have opportunistic fungus infections increased? The diagnosis of a fungus infection due to saprophytic pathogens is difficult, as the demonstration of a fungus does not necessarily imply disease. The case history with relevant predisposing factors is an essential clue to the diagnosis. As a matter of principle, the diagnosis of a systemic mycosis should only be established by exclusion.

Drug-Related Side Effects and Adverse Reactions↗
PubMed1992

Cryptococcus albidus isolated from pigeon excreta in Taiwan.

Cryptococcus albidus (Saito) Skinner, found frequently in the air of El-Minia, Egypt; in New Zealand and Budapest, and isolated occasionally from clinical specimens, has now been recognized as the cause of human diseases. Since isolation of this fungus from pigeon droppings has not previously been reported, this first paper reports results of its drug-susceptibility testing to gentamicin and 5-fluorocytosine, as well as its fungal cell antigenic cross reactivity with C. neoformans as detected by a Latex-Crypto-Antigen Detection System (LCAS).

Animals↗
PubMed2005

Suppression of Fusarium wilt by combining green compost and Trichoderma hamatum.

Fusarium wilts, caused by the fungus Fusarium oxysporum, are important diseases of horticultural and agricultural crops and lead to significant yield losses. The pathogen infects the roots and colonizes the vascular tissue, leading to wilting and finally death of the plant. The objective of this study was to investigate the efficacy of amendment of green compost and a Trichoderma hamatum strain against Fusarium wilt of radish. The substrate effects and the effect of a Trichoderma strain were tested in a potting soil bioassay. The tested composts lowered the disease level and had a positive influence on the plant yield (fresh weight and dry weight). Nothwithstanding, only a small dosis effect of the amendment was observed. In the presence of the tested Trichoderma hamatum strain no significant lower disease level was observed. Furthermore, a minor effect on plant yield (fresh weight and dry weight) was observed compared to the amendment with only green compost. Maybe the pathogenic Fusarium oxysporum strain and the Trichoderma strain competed for nutrients, iron could be a limiting factor. One possible approach to improve biological control may be the application of combinations of biocontrol agents.

Antibiosis↗
PubMed1991

Disseminated sporotrichosis in patients with AIDS: case report and review of the literature.

Sporotrichosis is the disease caused by the dimorphic fungus Sporothrix schenkii. Disseminated sporotrichosis is an uncommon infection which usually occurs in alcoholics or patients receiving immunosuppressive medication. We report a case of a patient with AIDS who had disseminated sporotrichosis which was progressive and fatal despite antifungal therapy. Four previously reported cases of disseminated sporotrichosis in patients with AIDS are reviewed. Disseminated sporotrichosis occurs in patients with HIV-1 infection and severe CD4 lymphocyte depletion. It usually presents with diffuse cutaneous lesions and is associated with polyarticular arthritis. Response to treatment is variable and chronic suppressive therapy is probably needed to prevent relapse.

Acquired Immunodeficiency Syndrome↗
PubMed2006

Northern Wisconsin married couple infected with blastomycosis.

Blastomycosis is an uncommon, chronic, granulomatous disease caused by the dimorphic fungus Blastomycosis dermatitidis. The great majority of infections start with primary pulmonary involvement through inhalation of spores. Hematogenous dissemination to other sites occurs in 25% to 30% of cases. The most common secondary site is the skin, followed in order by bone, genitourinary system, and central venous system. We report 2 cases of blastomycosis originating in a husband and wife who were both symptomatic and diagnosed with blastomycosis within 4 months of each other. One presented with pulmonary symptoms, the other with cutaneous symptoms. These 2 cases of husband and wife are of interest not only because of their rarity but also because of the potential mode of transmission.

Antifungal Agents↗
PubMed1996

Human pythiosis.

Pythiosis is a cosmopolitan granulomatous disease caused by an aquatic fungus Pythium insidiosum which usually occurs in horses, cattle, dogs, cats or fishes. There have been 28 cases of human pythiosis published in the literature. Twenty three patients have been reported from all over Thailand. Human pythiosis presents in one of three clinical forms: cutaneous or subcutaneous, systemic or vascular and ophthalmic (e.g., corneal ulcer or keratitis). Systemic antibiotics or antimycotics are not effective in the treatment of this infection. A saturated solution of KI gives a beneficial result only in the subcutaneous form. Surgical removal of the source of infection is the method of therapy of vascular and ophthalmic forms.

Animals↗