Meningitis and Ventriculitis due to Nocardia araoensis Infection.

A 73-year-old man was admitted to our hospital with disturbance of consciousness, fever and headache. Cerebrospinal fluid (CSF) analysis revealed pleocytosis with neutrophil predominance, increased protein and low glucose. CSF and blood cultures yielded negative results. Antibiotics and antituberculous drugs were started for meningitis. An antimycotic was also added. The patient died from transtentorial hernia 99 days after admission. Autopsy revealed meningitis, ventriculitis and brain abscess, and Nocardia araoensis was detected in pus from the left lateral ventricle. This appears to represent the first report of N. araoensis meningitis complicated by ventriculitis and brain abscess.

Identification of genes involved in the phosphate metabolism in Cryptococcus neoformans.

Cryptococcus neoformans is a pathogenic basidiomycetous yeast that can cause life-threatening meningoencephalitis in immuno-compromized patients. To propagate in the human body, this organism has to acquire phosphate that functions in cellular signaling pathways and is also an essential component of nucleic acids and phospholipids. Thus it is reasonable to assume that C. neoformans (Cn) possesses a phosphate regulatory system (PHO system) analogous to that of other fungi. By BLAST searches using the amino acid sequences of the components of the PHO system of Saccharomyces cerevisiae (Sc), we found potential counterparts to ScPHO genes in C. neoformans, namely, acid phosphatase (CnPHO2), the cyclin-dependent protein kinase (CDK) inhibitor (CnPHO81), Pho85-cyclin (CnPHO80), and CDK (CnPHO85). Disruption of each candidate gene, except CnPHO85, followed by phenotypic analysis, identified most of the basic components of the CnPHO system. We found that CnPHO85 was essential for the growth of C. neoformans, having regulatory function in the CnPHO system. Genetic screening and ChIP analysis, showed that CnPHO4 encodes a transcription factor that binds to the CnPHO genes in a Pi-dependent manner. By RNA-seq analysis of the wild-type and the regulatory mutants of the CnPHO system, we found C. neoformans genes whose expression is controlled by the regulators of the CnPHO system. Thus the CnPHO system shares many properties with the ScPHO system, but expression of those CnPHO genes that encode regulators is controlled by phosphate starvation, which is not the case in the ScPHO system (except ScPHO81). We also could identify some genes involved in the stress response of the pathogenic yeast, but CnPho4 appeared to be responsible only for phosphate starvation.

A genome sequence-based approach to taxonomy of the genus Nocardia.

The genus Nocardia includes both pathogens and producers of useful secondary metabolites. Although 16S rRNA analysis is required to accurately discriminate among phylogenetic relationships of the Nocardia species, most branches of 16S rRNA-based phylogenetic trees are not reliable. In this study, we performed in silico analyses of the genome sequences of Nocardia species in order to understand their diversity and classification for their identification and applications. Draft genome sequences of 26 Nocardia strains were determined. Phylogenetic trees were prepared on the basis of multilocus sequence analysis of the concatenated sequences of 12 genes (atpD-dnaJ-groL1-groL2-gyrB-recA-rpoA-secA-secY-sodA-trpB-ychF) and a bidirectional best hit. To elucidate the evolutionary relationships of these genes, the genome-to-genome distance was investigated on the basis of the average nucleotide identity, DNA maximal unique matches index, and genome-to-genome distance calculator. The topologies of all phylogenetic trees were found to be essentially similar to each other. Furthermore, whole genome-derived and multiple gene-derived relationships were found to be suitable for extensive intra-genus assessment of the genus Nocardia.