Fusobacterium nucleatum is classified as four subspecies, subsp. nucleatum, polymorphum, vincentii, and animalis, based on DNA-DNA hybridization (DDH) patterns, phenotypic characteristics, and/or multilocus sequence analysis (MLSA). The gold standards for classification of bacterial species are DDH and 16S ribosomal RNA gene (16S rDNA) sequence homology. The thresholds of DDH and 16S rDNA similarity for delineation of bacterial species have been suggested to be >70 and 98.65%, respectively. Average nucleotide identity (ANI) and genome-to-genome distance (GGD) analysis based on genome sequences were recently introduced as a replacement for DDH to delineate bacterial species with ANI (95-96%) and GGD (70%) threshold values. In a previous study, F. hwasookii was classified as a new species based on MLSA and DDH results. 16S rDNA similarity between F. hwasookii type strain and F. nucleatum subspecies type strains was higher than that between F. nucleatum subspecies type strains. Therefore, it is possible that the four F. nucleatum subspecies can be classified as Fusobacterium species. In this study, we performed ANI and GGD analyses using the genome sequences of 36 F. nucleatum, five F. hwasookii, and one Fusobacterium periodonticum strain to determine whether the four F. nucleatum subspecies could be classified as species using OrthoANI and ANI web-based softwares provided by ChunLab and Kostas lab, respectively, and GGD calculator offered by German Collection of Microorganisms and Cell Cultures. ANI values calculated from OrthoANI and ANI calculators between the type strains of F. nucleatum subspecies ranged from 89.80 to 92.97 and from 90.40 to 91.90%, respectively. GGD values between the type strains of F. nucleatum subspecies ranged from 42.3 to 46.0%. ANI and GGD values among strains belonging to the same F. nucleatum subspecies, subsp. nucleatum, subsp. polymorphum, subsp. vincentii, and subsp. animalis were >96 and >68.2%, respectively. These results strongly suggest that F. nucleatum subsp. nucleatum, subsp. polymorphum, subsp. vincentii, and subsp. animalis should be classified as F. nucleatum, F. polymorphum, F. vincentii, and F. animalis, respectively.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• The importance of efficient drug development using biomarkers has been increasingly emphasized, from preclinical studies to clinical trials.• However, as yet few 'validated' or 'qualified' biomarkers are used in early-stage drug development in terms of clinical pharmacology and disease pathophysiology. WHAT THIS STUDY ADDS• This first-time-in-human study provides evidence of the pharmacological activity of LC15-0444 in humans, by using dipeptidyl peptidase IV activity and active glucagon-like peptide-1 concentrations.• LC15-0444 possesses pharmacokinetic and pharmacodynamic characteristics that support a once-daily dosing regimen. AIMSLC15-0444 is a selective and competitive inhibitor of dipeptidyl peptidase (DPP) IV with potential for the treatment of Type 2 diabetes. The aim was to investigate the pharmacokinetic (PK) and pharmacodynamic (PD) profiles after multiple oral ascending doses of LC15-0444 in healthy male subjects. METHODSA dose block-randomized, double-blind, placebo-controlled, parallel group study was performed in three groups with 10 subjects (eight for active drug; two for placebo) per group; each group received 200, 400 or 600 mg of LC15-0444 once daily for 10 days. Blood and urine samples were collected up to 24 h after the first dosing and up to 72 h after the last dosing. RESULTSThe LC15-0444 concentration-time profiles exhibited characteristics of multicompartment disposition. No dose-or time-dependent change in PK parameters was observed. Mean elimination half-life was in a range 16.6-20.1 h in the dose groups. Mean renal clearance and fraction of unchanged drug excreted in urine was 18.6-21.9 and 0.40-0.48 l h -1 , respectively. In the steady state, mean accumulation ratios by dose groups were between 1.22 and 1.31. More than 80% inhibition of DPP IV activity from baseline was sustained for >24 h in all dose groups. CONCLUSIONSThis study provides evidence of the pharmacological activity of LC15-0444 in humans. LC15-0444 possesses PK and PD characteristics that support a once-daily dosing regimen.

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Five subspecies of Fusobacterium nucleatum have been classified: animalis, nucleatum, polymorphum, vincentii, and fusiforme. F. nucleatum subsp. animalis ChDC F324 (KCOM 1325) was isolated from a human subgingival plaque in the Republic of Korea. Here, we report the draft genome sequence of the strain.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Udenafil is a newly marketed phosphodiesterase type 5 (PDE5) inhibitor. • Udenafil is safe and well tolerated in healthy subjects, and effective as treatment for erectile dysfunction. • The effect of food on the pharmacokinetics of PDE5 inhibitors varies. WHAT THIS STUDY ADDS • This is the first study to determine the effect of food on the pharmacokinetics of udenafil. • Food generally does not affect the bioavailability of udenafil, although a low‐fat diet shows a tendency to decreases the absorption rate of udenafil. AIMS Udenafil is a cyclic guanosine 3′,5′‐monophosphate‐specific phosphodiesterase type 5 (PDE5) inhibitor developed for the treatment of erectile dysfunction. The aim was to evaluate the effect of food on the pharmacokinetics of udenafil. METHODS An open, randomized, three‐way crossover study was conducted. Fifteen healthy male volunteers received a single 200‐mg oral dose of udenafil while fasting, after a low‐fat meal, and after a high‐fat meal separated by 7‐day washout periods. Serial blood samples were taken up to 48 h after oral administration. RESULTS Under fasting conditions, udenafil was rapidly absorbed and tmax was observed typically 1.5 h after administration. The mean tmax values after a low‐fat meal and a high‐fat meal were 2.6 and 2.1 h, respectively. The ratios (90% confidence intervals) of the geometric means compared with the fasting condition for Cmax and AUClast were 0.79 (0.70, 0.90) and 0.96 (0.89, 1.03) in the low fat‐fed condition, respectively, and 1.01 (0.89, 1.15) and 1.03 (0.96, 1.11), respectively, in the high fat‐fed condition. CONCLUSIONS The tmax of udenafil was delayed under the fed conditions. However, although the Cmax was reduced by approximately 21% in the low fat‐fed state, overall bioavailability was not affected when taken with food.