Program and Abstracts of Annual Meeting of the Japanese Society for Medical Mycology

A quorum sensing substance farnesol and its several analogs have been found working as substances inhibiting filamentous growth in C. albicans (1). We examined the effects of such substances on the growth and dimorphism in C. tropicalis Pk233. Cells of this organism were incubated at 30°C with shaking either in defined meium containing glucose (0.11 M) as a carbon source (control culture medium, for yeast growth) or ethanol (0.43 M)-supplemented control one (ethanol culture medium, for pseudohyphal growth). Exogenous farnesol, 1-dodecanol or 1-decanol (<25 μM each) in the control culture medium gave normal yeast growth. However, in case of supplementing each of these substances into the ethanol culture medium, some delay in growth rates was found, followed by significant inhibition of pseudohyphal growth. In the case of farnesol supplementation, degree of the inhibition was the highest among these substances. These results suggest that farnesol might also play a quorum sensing role in yeast other than C. albicans .
(1) Hogan DA, Vik A, Kolter R (2004) Mol Microbiol 54(5):1212-23.

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Background: Following the introduction of highly active antiretroviral therapy (HAART), the prevalence of most opportunistic infection is declining. However, the beneficial effects of HAART on the occurrence of oral candidiase had not been entirely elucidated.
Methods: From August of 2003 to March 2004, we conducted a transversal study including 331 HIV-seropositive patients under HAART assisted in the University Hospital of Unicamp. Patients >18 years-old, without clinical evidence of oropharyngeal candidiasis and if they were undergoing a stable HAART regimen were enrolled. Specimens for fungal culture from oropharynx were collected by swab and oral Candida colonization was defined as the isolation of Candida spp. cultured in Sabouraud dextrose agar and CHROMagar. Identification to species was performed using API 20.
Results: Medium age was 38 years-old and 61.6% were male. One hundred and seven (44.4%) patients were colonized with Candida spp.. No difference was observed among patients receiving (171 patients) or not (132 patients) protease inhibitor (p=0.25). Median CD4 cell/mm, in colonizing and non colonizing patients, was 326 and 410 respectively (p=0.003) and viral load was undetectable in 59 out of 142 colonized patients and 114 out of 182 non colonized patients (p=0.0002). Mycological identification: C. albicans- 139; Candida non-albicans=22 (C. glabrata - 7; C.tropicalis -4; others-11).
Conclusions: the status of Candida carrier was associated with the number of CD4 cells and the viral load. The use of protease inhibitor did not influence the carriage of Candida spp.

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Aspergillus fumigatus produces several toxic secondary metabolites, such as gliotoxin, several toxic secondary metabolites, such as gliotoxin, fumagillin, helvolic acid, and others. Of the toxins detected in the hypha of Aspergillus fumigatus, fumagillin was well-known as an inhibitor of endothelial cell proliferation, tumor-induced angiogenesis, and tumor growth in mice, although it was known for nearly 40 years as a naturally secreted antibiotic of Aspergillus fumigatus used to treat human amoebiasis. In this study, we have tried to reveal the expression of TNF signaling genes by fumagillin in mouse macrophage (RAW264.7 cell) using multiplex PCR (MPCR), because these activity may be represented in both local and systemic inflammatory events during the fungal infection. MPCR data in this study showed that all of the TNF signaling genes, such as COX-2, NFκ-B, Fas, TNF-α, bcl-2, p53, and Iκ-B, were dose-dependently expressed at low concentration of fumagillin. These results suggest that fumagillin can be a critical role in the TNF signaling pathway causing inflammation and apoptosis during the fungal infection. Certainly, more tests and in-depth studies of this process are needed. Nevertheless, this study represents the first step in showing the effect of fumagillin on TNF signaling genes expression.

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The implementation of the diagnosis of candidemia is important for the prompt initiation of antifungal therapy. Two hundred and twenty-five patients with high risk for candidemia were prospectively followed-up, in a two year period. Blood cultures by automated BactAlert system and PCR from whole blood to detect candidemia were done in all patients, with more than 15 days of hospitalization in high risk areas. DNA was extracted and amplified using ITS5 and ITS4 base pair primers and the PCR products were sequenced for identification of Candida spp. Positive blood culture for Candida was considered the gold standard for candidemia diagnosis. Variables associated with the development of candidemia diagnosed by positive blood culture were also evaluated in the patients. The overall mortality of the patients was 26.1% and the mortality rate in candidemic and non-candidemic patients was 41.9% and 22.5%, respectively (p=0.009). PCR sensitivity and specificity were 72.1% and 91.2%, respectively. Positive and negative predictive values were: 65.9% and 93.2%, respectively. The logistic regression of the multivariate analysis showed that parenteral nutrition (p<.0001); fever (p=0.01); neutropenia (p=0.04) and urinary underlying catheter (p=0.02) were significant variables associated with the development of candidemia. The PCR technique followed by DNA sequencing was similar in the diagnosis of candidemia. In high risk patients with positive PCR for Candida spp., in blood sample, strongly suggested the diagnosis of candidemia.

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