Diagnosis and treatment of Candida albicans endocarditis can be difficult. We report a case of this rare condition in which a patient on oral fluconazole presented with septic pulmonary emboli without initial echocardiog...Diagnosis and treatment of Candida albicans endocarditis can be difficult. We report a case of this rare condition in which a patient on oral fluconazole presented with septic pulmonary emboli without initial echocardiographic evidence of vegetation. Rapid attainment of a tissue diagnosis, along with combined medical surgical treatment proved to be effective for this patient.
SCG is a 6-branched 1,3-β-D-glucan, and is a major cell wall structural component in fungi. The leukocytes from DBA/1 and DBA/2 mice are highly sensitive to SCG, producing cytokines, such as GM-CSF, IFN-γ and TNF-α. GM-C...SCG is a 6-branched 1,3-β-D-glucan, and is a major cell wall structural component in fungi. The leukocytes from DBA/1 and DBA/2 mice are highly sensitive to SCG, producing cytokines, such as GM-CSF, IFN-γ and TNF-α. GM-CSF plays a key biological role in this activity. We analyzed factors induced by SCG in splenocytes from DBA/2 mice by DNA microarray analysis on the condition of high sensitivity to β-glucan. Splenocytes were stimulated with SCG at 0, 24 or 30 h, and then supernatant was collected at 48 h to measure cytokines. SCG stimulated splenocytes to produce GM-CSF, IFN-γ and TNF-α in all the supernatants of 0, 24, and 30 h. The amount of IFN-γ production thus stimulated at 24 h was comparable to that at 0 h. Cytokine induction was observed at 4 h after SCG-stimulation even in the splenocytes pre-cultured for 36 h. The gene expression induced by SCG was analyzed with DNA microarray in the splenocytes in this condition. SCG up-regulated the expression of genes including Edn1 and Ptgs2 as well as genes associated with cytokine and chemokine. PGE(2) was detected in the medium of splenocytes stimulated with SCG. Taken together, these results indicated that splenocytes enhanced the sensitivity to SCG in earlier culture periods, and then responded to SCG to induce not only the cytokines but also various other factors.
A 26-year-old female (Case 1) presented with scaly erythema on the left cheek. Positive direct microscopic examination results indicated a diagnosis of tinea faciei. Colonies were isolated after incubation on Mycosel aga...A 26-year-old female (Case 1) presented with scaly erythema on the left cheek. Positive direct microscopic examination results indicated a diagnosis of tinea faciei. Colonies were isolated after incubation on Mycosel agar medium. Trichophyton mentagrophytes was morphologically identified based on giant colony formation and slide culture. Furthermore, nucleotide sequence analysis of the internal transcribed spacer 1 (ITS1) region of the rDNA gene identified Arthroderma vanbreuseghemii. The patient had 9 cats in her home, and similar colonies were isolated from 2 of these 9 cats by the hairbrush culture method. The isolated organism was identified as A. vanbreuseghemii , suggesting the cats to be the source of infection. An 11-year-old boy (Case 2) had palm-sized erythematous plaques from the nasal base to the area around the left eye and on the left cheek. Positive direct microscopic examination results indicated a diagnosis of tinea faciei. The patient had been treated with topical steroids for 6 weeks before the onset of these manifestations. The isolated organism was identified as A. vanbreuseghemii . His dog and two cats were tested but did not appear to be the source of infection. Since 2000, there have been 25 cases of tinea in Japan, identified as A. vanbreuseghemii by molecular biological techniques. Twelve cases had tinea on the face, and 11 had used topical steroids. A. vanbreuseghemii was found to be one of the important pathogens in tinea faciei.
The present taxonomic situation of pathogenic actinomycetes including Nocardia was clarified, and the impact of genomic sequence information of Nocardia farcinica IFM 10152 on taxonomic work is introduced. The number of...The present taxonomic situation of pathogenic actinomycetes including Nocardia was clarified, and the impact of genomic sequence information of Nocardia farcinica IFM 10152 on taxonomic work is introduced. The number of cases of nocardiosis is on the rise along with the increasing number of immunocompromised patients in Japan. From 1999 to 2007, 718 strains of pathogenic actinomycetes were received for identification by Medical Mycology Research Center (MMRC), Chiba University. About 75% of these were classified into Nocardia, major species being N. farcinica, N. nova, and N. brasiliensis. Among the strains classified as Nocardia species, there were some unclassifiable strains and taxonomic studies on these led to the proposal of more than 18 new species, resulting in more than 1/4 of all Nocardia species having been proposed by our group. Recently a new Nocardia species, Nocardia mikamii was proposed by American researchers. A new phylogenetic analysis method using gryB and secA1 genes was proposed for the Nocardia and Gordonia strains.Our whole genome analysis of N. farcinica suggests that the bacterium has unique and characteristic gene profiles, and also suggests that N. farcinica is similar to Mycobacterium tuberculosis. N. farcinica also has siderophore (nocobactin) and mce genes which are similar to mycobactin (siderophore) of M. tuberculosis as virulence factors. Nocardia strains were found to be producers of new secondary metabolites including antifungal, antitumor and immunosuppressive activities.We reported novel antibiotic resistance mechanisms such as ribosylation, glucosylation, phosphorylation and degradation of rifampicin, phosphorylation of aminoglycosides, and glucosylation of macrolide antibiotics. Among rifampicin inactivation mechanisms, ribosylation was found to be through the Arr enzyme that catalyzes ADP-ribosylation of rifampicin in a fast-growing Mycobacterium smegmatis. This unique mechanism has also been reported as an antibiotic resistant mechanism in pathogenic Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Acinetobacter baumannii.Our cooperative work on the elucidation of high-level resistance to the aminoglycoside antibiotic amikacin in N. farcinica with a research group from CDC, USA, revealed the presence of homozygous mutations in the 16R rRNA genes which are responsible for high-level aminoglycoside antibiotic resistance.
Antifungal susceptibility tests were performed for 38 Candida albicans strains isolated from oral cavities of 43 Uighurian AIDS patients. Results showed that six isolates were resistant to fluconazole; one showed low sus...Antifungal susceptibility tests were performed for 38 Candida albicans strains isolated from oral cavities of 43 Uighurian AIDS patients. Results showed that six isolates were resistant to fluconazole; one showed low susceptibility. We attempted to examine these strains molecular-epidemiologically, but 25S rDNA genotyping was insufficient for their discrimination. To estimate whether the origins of resistant strains were identical, we developed a new combination method of C. albicans tandem repeating units (ALTS)/RFLP and micro-temperature gradient gel electrophoresis (micro-TGGE). This new method was able to distinguish all seven strains. A suspected nosocomial infection was ruled out.
The Japanese Society for Medical Mycology (JSMM) method used for testing the antifungal susceptibility of yeast, the MIC end point for azole antifungal agents, is currently set at IC(80). It was recently shown, however t...The Japanese Society for Medical Mycology (JSMM) method used for testing the antifungal susceptibility of yeast, the MIC end point for azole antifungal agents, is currently set at IC(80). It was recently shown, however that there is an inconsistency in the MIC value between the JSMM method and the CLSI M27-A2 (CLSI) method, in which the end- point was to read as IC(50). To resolve this discrepancy and reassess the JSMM method, the MIC for three azoles, fluconazole, itraconazole and voriconazole were compared to 5 strains of each of the following Candida species: C. albicans, C. glabrata, C. tropicalis, C. parapsilosis and C. krusei, for a total of 25 comparisons, using the JSMM method, a modified JSMM method, and the CLSI method. The results showed that when the MIC end- point criterion of the JSMM method was changed from IC(80) to IC(50) (the modified JSMM method) , the MIC value was consistent and compatible with the CLSI method. Finally, it should be emphasized that the JSMM method, using a spectrophotometer for MIC measurement, was superior in both stability and reproducibility, as compared to the CLSI method in which growth was assessed by visual observation.
Three genetically hybrid F1 progenies produced between a clinical isolate of Arthroderma simii (KMU4810) and a tester strain of A. vanbreuseghemii (RV27961) were crossed with two tester strains of A. vanbreuseghemii (RV2...Three genetically hybrid F1 progenies produced between a clinical isolate of Arthroderma simii (KMU4810) and a tester strain of A. vanbreuseghemii (RV27961) were crossed with two tester strains of A. vanbreuseghemii (RV27961 and RV27960) and a tester strain of A. benhamiae (RV30001), respectively. Three crossings yielded hybrid second progenies. Another interspecies crossing between A. simii (KMU4810) and a tester strain of A. benhamiae (RV26680) yielded one hybrid F1 progeny (Asb57). The second crossings of F1 progeny (Asb57) with A. vanbreuseghemii (RV27961) and A. benhamiae (RV30001) yielded many hybrid second progenies. Some hybrid second progenies produced between F1 progeny and A. vanbreuseghemii were confirmed to have genes from three species. The gene exchangeability among three Arthroderma species was shown and the meaning of these events discussed.
We assessed the potential of oligonol, a low molecular polyphenol formulation prepared from lychee fruits, for treatment of oral candidiasis using a murine model. Oligonol at concentration of more than 313 microg/ml inhi...We assessed the potential of oligonol, a low molecular polyphenol formulation prepared from lychee fruits, for treatment of oral candidiasis using a murine model. Oligonol at concentration of more than 313 microg/ml inhibited the mycelial growth of Candida albicans in vitro. When 50 microl of oligonol (20 mg/ml ) was administered three times into the oral cavity of orally Candida -infected mice, the number of viable Candida cells in the oral cavity was reduced significantly and the score of lesions on the tongue recovered on day 2. These findings suggest that oligonol could have potential as a food component supporting anti- Candida treatment.
Cell surface hydrophobicity (CSH) of 50 clinical isolates of Candida albicans was studied, and values varied broadly in the range 2% to 41%. Purpose of the present work was to investigate correlation of CSH with the C. a...Cell surface hydrophobicity (CSH) of 50 clinical isolates of Candida albicans was studied, and values varied broadly in the range 2% to 41%. Purpose of the present work was to investigate correlation of CSH with the C. albicans adherence to solid surfaces, if any. To elucidate this, adhesion to the polystyrene model surface was studied for all the clinical isolates. Adherence varied in the range of 79 to 478 cells per microscopic field. Results indicated no correlation between CSH of the clinical isolates and their adhesion to polystyrene.
The clinical presentation of dermatophytosis depends on species of the infecting fungus. The infections caused by the anthropophilic species tend to be chronic and intractable, and the resultant inflammation is minimal....The clinical presentation of dermatophytosis depends on species of the infecting fungus. The infections caused by the anthropophilic species tend to be chronic and intractable, and the resultant inflammation is minimal. On the other hand, the infections caused by the geophilic and zoophilic species tend to be self-healing, and the resultant inflammation is more severe. We investigated the role of cytokine secretion of human keratinocyte during dermatophyte infections: Arthroderma benhamiae, a zoophilic dermatophyte, and Trichophyton tonsurans, an anthropophilic dermatophyte. The results demonstrate that keratinocytes secrete a broad spectrum of cytokines including proinflammatory cytokines, chemokines, and immunomodulatory cytokines in response to A. benhamiae infection, whereas T.tonsurans infection stimulates the production of only a limited number of cytokines. Such differential cytokine secretion of the keratinocytes in response to infection by dermatophyte species may reflect the distinct inflammatory responses in the skin.
Aspergillosis is an important mycosis caused primarily by Aspergillus fumigatus and its relatives. The genus Emericella is a teleomorph related to the Aspergillus section Nidulantes. The typical anamorphic stage species...Aspergillosis is an important mycosis caused primarily by Aspergillus fumigatus and its relatives. The genus Emericella is a teleomorph related to the Aspergillus section Nidulantes. The typical anamorphic stage species in this genus is Aspergillus nidulans, which is sometimes a significant agent in chronic granulomatous disease (CGD) patients. The mortality rate of osteomyelitis in CGD patients due to A. nidulans ( E. nidulans ) is very high compared to that due to A. fumigatus. Moreover, two Emericella species ( E. nidulans and E. quadrilineata ) from clinical specimens exhibit different sensitivities against several antifungal drugs. In aspergillosis, correct species identification is important for antifungal therapy. We attempted to develop rapid and specific molecular discrimination by polymerase chain reaction (PCR) and loop-mediated isothermal amplification (LAMP) methods in the principal pathogenic Emericella species, and succeeded in establishing species-specific primers corresponding to the hydrophobin gene. These primers discriminate E. nidulans and E. quadrilineata rapidly and specifically. These methods and primers make it possible to diagnose etiological agents in aspergillosis quickly and easily.
beta-Glucan is a major component of the cell walls and pathogen-associated microbial patterns of fungi. We previously reported the presence of an antibody which reacts to beta-glucan, anti-beta-glucan (BG) antibody, in h...beta-Glucan is a major component of the cell walls and pathogen-associated microbial patterns of fungi. We previously reported the presence of an antibody which reacts to beta-glucan, anti-beta-glucan (BG) antibody, in human sera. In livestock and domestic pets, the antibody's response to fungal cell wall beta-glucan is little understood. In this study, we examined the existence and reactivity of anti-BG antibody in various animal species. We demonstrated the presence of the anti-BG antibody in each animal's serum. Individual differences in the titer existed. The antibody was highly reactive to Candida solubilized cell wall beta-glucan (CSBG) while reacting little to grifolan (GRN) from Grifola frondosa. This suggested that the anti-BG antibody interacted with fungal cell wall beta-glucan and participated in the immune-response to pathogenic fungi.
We report a case of subcutaneous abscess caused by Nocardia farcinica in a 44-year-old man, who had been treated with systemic prednisolone and cyclosporin for aplastic anemia. He had been affected by aplastic anemia for...We report a case of subcutaneous abscess caused by Nocardia farcinica in a 44-year-old man, who had been treated with systemic prednisolone and cyclosporin for aplastic anemia. He had been affected by aplastic anemia for 8 years, and was previously treated with antithymocyte globulin. The effect was insufficient, and platelet and erythrocyte transfusion was required. Bone marrow transplantation was not adopted due to a psychological problem. He had also been treated with prednisolone and cyclosporin for 3 years. Without apparent cause, swelling and pain of left upper extremity developed in April, 2008. There was no abnormality in cutaneous macroscopic findings, such as a wound or a sting. He was administered antibiotics, but they were ineffective and effusion were excreted into the skin. After hospitalization, he was treated by incision and drainage and antibiotics were started. The pathogen was identified as Nocardia farcinica by its biochemical characters. There was no dissemination to other organs like lung or brain and he recovered completely with a treatment of antibiotics for 1 year. We studied the epidemiological and clinical characteristics of Nocardia infections reported in Japan from 2000 to 2008 and identified 92 cases using the medical article search engine Ichushi-Web (Japan Medical Abstract Society). The results indicate that the most important risk factor in systemic nocardiosis ia an immunosuppressive agent such as prednisolone, cyclosporine, or azathioprine. We believe that we should take the possibility of Nocardia infection into consideration in a compromised host.
Molecular biological approaches have recently begun to be applied to molecular genetics studies of dermatophytes. High-throughput gene analysis methodologies, such as EST sequencing, differential cDNA screening, and cDNA...Molecular biological approaches have recently begun to be applied to molecular genetics studies of dermatophytes. High-throughput gene analysis methodologies, such as EST sequencing, differential cDNA screening, and cDNA-based microarray analysis have been used to obtain information on many dermatophyte genes and their expression profiles under different experimental conditions. In addition, whole genome sequencing projects are underway for several important dermatophytes, such as Trichophyton rubrum and Microsporum canis. These studies will provide large amounts of valuable information for elucidating the molecular basis of host invasion by dermatophytes and their virulence. Targeted gene disruption by homologous recombination is one of the most common approaches for determining the functions and roles of numerous genes isolated from pathogenic fungi. However, the difficulty of genetic manipulation due to low transformation frequency of dermatophytes may limit the successful production of null mutants by targeted gene disruption via homologous recombination. To overcome these problems, our group has developed useful genetic manipulation systems for dermatophytes using the clinically important dermatophyte, T. mentagrophytes.
Systemic fungal infections, caused by a wide variety of fungi, contribute to high mortality in humans with immunocompromised conditions. However, there are few classes of antifungal drugs available, limiting therapeutic...Systemic fungal infections, caused by a wide variety of fungi, contribute to high mortality in humans with immunocompromised conditions. However, there are few classes of antifungal drugs available, limiting therapeutic options. Azoles are the most commonly used class of antifungals to treat many fungal infections, but resistance to azoles can be induced or, for some fungi, is an inherent property. One of major mechanisms of azole resistance is overexpression of drug efflux pumps in fungal cell membranes, such as the energy-dependent ATP-binding cassette (ABC) transporters. We have developed a protein hyperexpression system to facilitate functional analysis of efflux pumps using a Saccharomyces cerevisiae strain as the host for heterologous expression. The system is well suited for the hyperexpression of individual fungal ABC transporters for structural and functional studies. Furthermore, the recombinant yeast strains expressing heterologous membrane proteins can be used to screen for compounds that overcome fungal drug resistance. Also in this review, the mechanisms of azole resistance in Candida glabrata and C. krusei will be considered in relation to the recent increase in the incidence of Candida infections caused by non-albicans Candida. The development of possible novel antifungal agents will also be discussed.
In recent years, incidence of invasive fungal infection has been increasing, mostly due to advances in + medicine that may produce immunocompromised individuals. Candidial infection in the central nervous system (CNS) is...In recent years, incidence of invasive fungal infection has been increasing, mostly due to advances in + medicine that may produce immunocompromised individuals. Candidial infection in the central nervous system (CNS) is one of the most serious forms of blood stream infection of Candida sp. and mortality is known to be more than 50%. In this research, we employed 27 autopsies with confirmed in vasive CNS yeast infection which were confirmed. In addition to detailed morphological analysis of yeast cells in lesions, in situ hybridization was carried out with an originally designed Candida-specific peptide nucleic acid (PNA) probe to identify the candidial infection of each patient. This was followed by histopathological investigation: invasiveness, shape, and distribution of yeast or yeasts with pseudohyphal growth, and a study regarding the correlation between histological characteristics and number of leukocytes in the peripheral blood just before death. Results showed that the, supratentorial region was the most common area of disseminated candidial infection in CNS, and that density was highest in the cerebral gray matter followed by the white matter and basal ganglia. On the other hand, regarding the lesions developed in the cortical area, the average distance from the brain surface was 4.026 mm. This area corresponding to the deeper cortex has a characteristic arterial structure that refers hairpin curving reverse. The structure may contribute to the high incidence of candidial foci in the deeper cortex, because of the increase in shear stress.
BACKGROUND: Onychomycosis represents the most frequently encountered nail disease, which is difficult to eradicate with drug treatment. AIM: This study was undertaken to document the clinico-mycological pattern of onycho...BACKGROUND: Onychomycosis represents the most frequently encountered nail disease, which is difficult to eradicate with drug treatment. AIM: This study was undertaken to document the clinico-mycological pattern of onychomycosis in Iran. Results of mycological tests of nail scrapings collected over a 4-year period were analyzed. METHODS: Both direct microscopy and cultures of the nail material were performed to identify the causative agents. RESULTS: The microscopic and/or cultural detection of fungi was positive in 40.2% of samples. The most common clinical type noted was distolateral subungual onychomycosis in 48.4% of cases. Etiological fungal agents were 50% dermatophytes, 46.8% yeasts, and 3.2% saprophytic moulds. The most frequently detected dermatophyte species were Trichophyton rubrum (48.4%) and T. mentagrophytes (41.9%). Among yeasts, Candida albicans (58.6) was most common, followed by C. parapsilosis (17.2%), C. glabrata (10.3%), C. krusei and C. tropicalis (each 6.9%). Aspergillus niger and A. flavus were the most frequent saprophytic moulds. Females were affected more frequently than males, and in both sexes those most infected were between 40-49 years of age. Fingernails were affected more frequently than toenails. CONCLUSIONS: The clinico-epidemiological data collected can serve as reference for future research and may be useful in the development of preventive and educational strategies.
We examined the effects of spices and herbs on Candida albicans growth using in vitro assay and therapeutic activity of some selected herbal preparations against murine oral candidiasis. All tested samples: lemongrass (C...We examined the effects of spices and herbs on Candida albicans growth using in vitro assay and therapeutic activity of some selected herbal preparations against murine oral candidiasis. All tested samples: lemongrass (Cymbopogon citratus), lemon balm (Melissa officinalis), thyme (Thymus vulgaris), rosemary (Rosmarinus officinalis), roselle (Hibiscus sabdariffa), green tea (Camellia sinensis), and cassia (Cinnamomum cassia) inhibited Candida mycelial growth in vitro. The results of this assay showed that the anti-Candida activity of lemongrass, green tea, and cassia is stronger than that of the other tested herbs. Oral administration of lemongrass or green tea did not result in significant improvement in the murine oral candidiasis, while the administration of cassia improved the symptoms and reduced the number of viable Candida cells in the oral cavity. The results of in vitro Candida growth assay including GC/MS analysis suggested that cinnamaldehyde in the cassia preparation was the principal component responsible for the inhibitory activity of Candida mycelial growth. These findings suggest that oral intake of a cassia preparation is a clinical candidate for a prophylactic or therapeutic tool against oral Candida infection.
To evaluate the anti-inflammatory activity of the thiocarbamate antifungal agent liranaftate, the edema and the neutrophil accumulation detected by the activity of neutrophil marker enzyme, myeloperoxidase (MPO), were ex...To evaluate the anti-inflammatory activity of the thiocarbamate antifungal agent liranaftate, the edema and the neutrophil accumulation detected by the activity of neutrophil marker enzyme, myeloperoxidase (MPO), were examined following application of liranaftate to mouse ears with inflammation induced by phorbol 12-myristate 13-acetate (PMA). Topical 20 microl administration of liranaftate in a dose-range between 1-4% suppressed the increase in ear thickness 6 hr after PMA application dose-dependently. Similarly, it decreased the weight increase of an ear section after 24 hr dose-dependently. More than 1% of liranaftate also suppressed augmentation of MPO activity of the ear section. This and histological observation indicate that liranaftate treatment suppressed neutrophil accumulation in PMA-applied ear lesion. From these results, we discussed that liranaftate might suppress inflammatory symptoms caused by trychophytosis in a clinical condition.