A deep-branching clade of Thaumarchaeota, conventionally called Terrestrial hot spring creanarchaeotic group (THSCG), is a missing link between thaumarchaeotic ammonia oxidizers and the deeper-branching non-ammonia oxidizers, such as Crenarchaeota and Candidatus Korarchaeota. Here, we report isolation of the first cultivated representative from the THSCG, named as NAS-02. Physiological characterization demonstrated that the isolate was a thermoacidophilic, sulfurand iron-reducing organoheterotroph, which was supported by gene contents encoded in its complete genome. There was no evidence for ammonia oxidation by the isolate. Members in THSCG are likely thermophiles, and may play roles in degrading cell debris as a scavenger and in biogeochemical cycling of sulfur and iron in the hot environments, as suggested by the physiological characteristics of the isolate and the geographical distribution of the 16S rRNA gene sequences of THSCG in terrestrial hot springs and marine hydrothermal fields. Phylogenetic analysis suggests that the THSCG lineage represented by NAS-02 has gained the ability of sulfur reduction via horizontal gene transfer. Based on the phylogeny and physiology, we propose the name Conexivisphaera calidus gen. nov., sp. nov. to accommodate the isolate.

There were no significant differences in the pharmacokinetics of micafungin and expression of hepatic multidrug resistance-associated protein 2 (ABCC2/Mrp2) between analbuminemic and Sprague-Dawley rats. Micafungin bound strongly to high-density lipoprotein (HDL) and moderately to gamma globulin. These results suggest that HDL and gamma globulin contribute to the pharmacokinetics of micafungin.Micafungin is widely used for the treatment and prevention of various fungal infections. This antibiotic appears to be predominantly eliminated by hepatic cytochrome P450 (CYP)-mediated metabolism and partly excreted in unchanged form in the feces via hepatobiliary excretion, whereas urinary excretion is a minor excretion route (6,12,20). Moreover, it has also been reported that micafungin has no effect on the metabolism of various substrates for CYP isoforms such as CYP3A4, CYP1A2, and CYP2C9 (4,5,14,16). We have recently demonstrated that micafungin is excreted into bile mainly by multidrug resistance-associated protein 2 (ABCC2/Mrp2) and partly by ABCB1/P-glycoprotein, and its plasma protein binding level is very high (Ͼ99%) in Sprague-Dawley (SD) rats (1). The effect of plasma protein binding on the pharmacokinetics of micafungin, however, is not clear yet.Nagase analbuminemic rats, which have been established from SD rats, are characterized by a considerably low plasma albumin concentration and hyperlipidemia (13). Many studies regarding the pharmacokinetic characteristics of various drugs in Nagase analbuminemic rats have been published (2,3,(7)(8)(9)18).The present study aims to clarify the role of plasma proteins such as albumin, high-density lipoprotein (HDL), and gamma globulin in the pharmacokinetics of micafungin in analbuminemic rats.Standard solutions of micafungin and FR195743 (an internal standard) were kindly supplied by Astellas Pharma Inc. (Tokyo, Japan). Micafungin for injection was purchased commercially. Human serum albumin (HSA) was obtained from Sigma Chemicals (St. Louis, MO). Human HDL and gamma globulin were purchased from Wako Chemicals (Tokyo, Japan). C219 mouse monoclonal antibody to P-glycoprotein (Dako, Glostrup, Denmark), human monoclonal antibody against Mrp2 (Alexis Biochemicals, San Diego, CA), mouse monoclonal antibody to ␤-actin (Sigma), and horseradish peroxidase-conjugated anti-mouse immunoglobulin G (GE Healthcare UK Ltd., Buckinghamshire, United Kingdom) were used for Western blotting. All other reagents were obtained commercially and were of the highest purity available. Micafungin, HSA, gamma globulin, and HDL were dissolved in saline.Male SD rats (8 weeks old; body weight, 270 to 295 g) and male Nagase analbuminemic rats (body weight, 225 to 250 g) of the same age as the SD rats were obtained from Japan SLC Inc. (Hamamatsu, Japan). The rats were housed under controlled environmental conditions (temperature of 23 Ϯ 1°C and humidity of 55% Ϯ 5%) with a commercial diet and water freely available. All animal experiments were carried out in accordance with the guidelines of Aichi Med...

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