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.

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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.

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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 30h. 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. PGE₂ 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.

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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.

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