Sooyeon Park

Donor-Derived Natural Killer Cells Infused after Human Leukocyte Antigen–Haploidentical Hematopoietic Cell Transplantation: A Dose-Escalation Study

The doses of donor-derived natural killer (NK) cells that can be given safely after human leukocyte antigen (HLA)-haploidentical hematopoietic cell transplantation (HCT) remain to be defined. Forty-one patients (ages 17 to 75 years) with hematologic malignancy underwent HLA-haploidentical HCT after reduced-intensity conditioning containing busulfan, fludarabine, and antithymocyte globulin. Cell donors (ages 7 to 62 years) underwent growth factor-mobilized leukapheresis for 3 to 4 days. Cells collected on the first 2 to 3 days were used for HCT, whereas those collected on the last day were CD3-depleted and cultured into NK cells using human interleukins-15 and -21. These NK cells were then infused into patients twice at 2 and 3 weeks after HCT at an escalating doses of .2 × 10(8) cells/kg of body weight (3 patients), .5 × 10(8) cells/kg (3 patients), 1.0 × 10(8) cells/kg (8 patients), and ≥ 1.0 × 10(8) cells/kg or available cells (27 patients). At all dose levels, no acute toxicity was observed after NK cell infusion. After HLA-haploidentical HCT and subsequent donor NK cell infusion, when referenced to 31 historical patients who had undergone HLA-haploidentical HCT after the same conditioning regimen but without high-dose NK cell infusion, there was no significant difference in the cumulative incidences of major HCT outcomes, including engraftment (absolute neutrophil count ≥ 500/μL, 85% versus 87%), grade 2 to 4 acute graft-versus-host disease (GVHD, 17% versus 16%), moderate to severe chronic GVHD (15% versus 10%), and transplantation-related mortality (27% versus 19%). There was, however, a significant reduction in leukemia progression (74% to 46%), with post-transplantation NK cell infusion being an independent predictor for less leukemia progression (hazard ratio, .527). Our findings showed that, when given 2 to 3 weeks after HLA-haploidentical HCT, donor-derived NK cells were well tolerated at a median total dose of 2.0 × 10(8) cells/kg. In addition, they may decrease post-transplantation progression of acute leukemia.

Exceptional Production of both Prodigiosin and Cycloprodigiosin as Major Metabolic Constituents by a Novel Marine Bacterium, Zooshikella rubidus S1-1

ABSTRACT A Gram-negative, red-pigment-producing marine bacterial strain, designated S1-1, was isolated from the tidal flat sediment of the Yellow Sea, Korea. On the basis of phenotypic, phylogenetic, and genetic data, strain S1-1 (KCTC 11448BP) represented a new species of the genus Zooshikella. Thus, we propose the name Zooshikella rubidus sp. nov. Liquid chromatography and mass spectrometry of the red pigments produced by strain S1-1 revealed that the major metabolic compounds were prodigiosin and cycloprodigiosin. In addition, this organism produced six minor prodigiosin analogues, including two new structures that were previously unknown. To our knowledge, this is the first description of a microorganism that simultaneously produces prodigiosin and cycloprodigiosin as two major metabolites. Both prodigiosin and cycloprodigiosin showed antimicrobial activity against several microbial species. These bacteria were approximately 1.5-fold more sensitive to cycloprodigiosin than to prodigiosin. The metabolites also showed anticancer activity against human melanoma cells, which showed significantly more sensitivity to prodigiosin than to cycloprodigiosin. The secondary metabolite profiles of strain S1-1 and two reference bacterial strains were compared by liquid chromatography-mass spectrometry. Multivariate statistical analyses based on secondary metabolite profiles by liquid chromatography-mass spectrometry indicated that the metabolite profile of strain S1-1 could clearly be distinguished from those of two phylogenetically related, prodigiosin-producing bacterial strains.

Roseovarius halocynthiae sp. nov., isolated from the sea squirt Halocynthia roretzi

A Gram-negative, non-motile, rod-shaped bacterial strain, designated MA1-6T, was isolated from a sea squirt (Halocynthia roretzi) collected from the South Sea, Korea, and was characterized to determine its taxonomic position. Strain MA1-6T grew optimally at pH 7.0-8.0, at 30 °C and in the presence of 2-3u200a% (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain MA1-6T fell within the clade comprising Ruegeria species and exhibited 95.3-96.5u200a% similarity to the type strains of recognized Ruegeria species. Strain MA1-6T contained Q-10 as the predominant ubiquinone and C18:1ω7c as the major fatty acid, which is consistent with data for Ruegeria species. The major polar lipids detected in strain MA1-6T and Ruegeria atlantica KCTC 12424T were phosphatidylcholine, phosphatidylglycerol, an unidentified aminolipid and an unidentified lipid. The DNA G+C content of strain MA1-6T was 58.6 mol%. Differential phenotypic properties, together with phylogenetic distinctiveness, demonstrated that strain MA1-6T can be distinguished from recognized Ruegeria species. On the basis of phenotypic, chemotaxonomic and phylogenetic data, strain MA1-6T is considered to represent a novel species of the genus Ruegeria, for which the name Ruegeria halocynthiae sp. nov. is proposed; the type strain is MA1-6T (=KCTC 23463T=CCUG 60744T).

Lysinibacillus xylanilyticus sp. nov., a xylan- degrading bacterium isolated from forest humus

A novel xylan-degrading bacterium, designated XDB9(T), was isolated from forest humus collected from Gyeryong Mountain in Korea. Cells were Gram-positive, aerobic, motile and endospore-forming rods. A neighbour-joining phylogenetic tree based on 16S rRNA gene sequences showed that strain XDB9(T) was most closely related to members of the genus Lysinibacillus. 16S rRNA gene sequence similarities between strain XDB9(T) and the type strains of species of the genus Lysinibacillus ranged from 98.0 to 98.5 %. The cell-wall peptidoglycan type of strain XDB9(T) was A4alpha, which is based on L-Lys-D-Asp. Strain XDB9(T) contained iso-C(15 : 0) and C(16 : 1)omega7c alcohol as the major fatty acids and MK-7 as the predominant menaquinone. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. The DNA G+C content was 37.2 mol%. The DNA-DNA hybridization results and differential phenotypic properties showed that strain XDB9(T) could be distinguished from recognized species of the genus Lysinibacillus. It was concluded that strain XDB9(T) represents a new taxon for which the name Lysinibacillus xylanilyticus sp. nov. is proposed. The type strain is XDB9(T) (=KCTC 13423(T)=CCUG 57438(T)).

Mucilaginibacter litoreus sp. nov., isolated from marine sand

A Gram-staining-negative, non-spore-forming, facultatively anaerobic, non-flagellated, non-gliding, rod-shaped bacterium, designated strain BR-18(T), was isolated from marine sand collected on the western coast of South Korea. The taxonomic position of the novel strain was determined using a polyphasic approach. Strain BR-18(T) grew optimally at 25 °C, at pH 6.5-7.0 and in the absence of NaCl. In phylogenetic analyses based on 16S rRNA gene sequences, the novel strain fell within a clade comprising members of the genus Mucilaginibacter and appeared most closely related to Mucilaginibacter lutimaris BR-3(T) (96.6 % sequence similarity) and Mucilaginibacter rigui WPCB133(T) (95.9 %). The novel strain showed lower levels of 16S rRNA gene sequence similarity with the type strains of other members of the genus Mucilaginibacter (93.4-95.5 %) and those of other species included in the phylogenetic analyses (<91.6 %). Strain BR-18(T) contained MK-7 as its predominant menaquinone, summed feature 3 (C(16 : 1)ω7c and/or iso-C(15 : 0) 2-OH) and iso-C(15 : 0) as its major fatty acids, phosphatidylethanolamine and an unidentified aminophospholipid as its major polar lipids, and sphingolipids. The genomic DNA G+C content of the novel strain was 42.4 mol%. Based on the phylogenetic and phenotypic data, strain BR-18(T) represents a novel species of the genus Mucilaginibacter, for which the name Mucilaginibacter litoreus sp. nov. is proposed. The type strain is BR-18(T) (u200a= KCTC 23697(T) u200a= CCUG 61484(T)).

Ohtaekwangia koreensis gen. nov., sp. nov. and Ohtaekwangia kribbensis sp. nov., isolated from marine sand, deep-branching members of the phylum Bacteroidetes

Two Gram-stain-negative, non-motile, non-spore-forming, rod-shaped bacterial strains, designated 3B-2(T) and 10AO(T), were isolated from a sand sample collected from the west coast of the Korean peninsula by using low-nutrient media, and their taxonomic positions were investigated in a polyphasic study. The strains did not grow on marine agar. They grew optimally at 30 °C and pH 6.5-7.5. Strains 3B-2(T) and 10AO(T) shared 97.5 % 16S rRNA gene sequence similarity and mean level of DNA-DNA relatedness of 12 %. In phylogenetic trees based on 16S rRNA gene sequences, strains 3B-2(T) and 10AO(T), together with several uncultured bacterial clones, formed independent lineages within the evolutionary radiation encompassed by the phylum Bacteroidetes. Strains 3B-2(T) and 10AO(T) contained MK-7 as the predominant menaquinone and iso-C(15 : 0) and C(16 : 1)ω5c as the major fatty acids. The DNA G+C contents of strains 3B-2(T) and 10AO(T) were 42.8 and 44.6 mol%, respectively. Strains 3B-2(T) and 10AO(T) exhibited very low levels of 16S rRNA gene sequence similarity (<85.0 %) to the type strains of recognized bacterial species. These data were sufficient to support the proposal that the novel strains should be differentiated from previously known genera of the phylum Bacteroidetes. On the basis of the data presented, we suggest that strains 3B-2(T) and 10AO(T) represent two distinct novel species of a new genus, for which the names Ohtaekwangia koreensis gen. nov., sp. nov. (the type species; type strain 3B-2(T) u200a=u200aKCTC 23018(T) u200a=u200aCCUG 58939(T)) and Ohtaekwangia kribbensis sp. nov. (type strain 10AO(T) u200a=u200aKCTC 23019(T) u200a=u200aCCUG 58938(T)) are proposed.

Thalassobius maritimus sp. nov., isolated from seawater

A Gram-stain-negative, aerobic, motile, rod-shaped bacterial strain, GSW-M6(T), was isolated from seawater of Geoje island, Korea, and was subjected to a polyphasic taxonomic study. Strain GSW-M6(T) grew optimally at pH 7.0-8.0, at 30 °C and in the presence of 2% (w/v) NaCl. In the neighbour-joining phylogenetic tree based on 16S rRNA gene sequences, strain GSW-M6(T) clustered with Thalassobius aestuarii, Thalassobius gelatinovorus and Thalassobius mediterraneus. Strain GSW-M6(T) exhibited 96.2-96.9% 16S rRNA gene sequence similarity to the type strains of these three Thalassobius species. Strain GSW-M6(T) contained Q-10 as the predominant ubiquinone and C(18:1)ω7c as the major fatty acid. The polar lipid profiles of strain GSW-M6(T) and the type strains of the three Thalassobius species were similar, with phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine and an unidentified lipid as common major components. The DNA G+C content of strain GSW-M6(T) was 57 mol%. The mean level of DNA-DNA relatedness between strain GSW-M6(T) and the type strain of Thalassobius gelatinovorus was 17%. Differential phenotypic properties, together with the phylogenetic and genetic distinctiveness, enabled strain GSW-M6(T) to be differentiated from recognized species of the genus Thalassobius. On the basis of the data presented, strain GSW-M6(T) is considered to represent a novel species of the genus Thalassobius, for which the name Thalassobius maritimus sp. nov. is proposed. The type strain is GSW-M6(T) (=KCTC 23347(T) =CCUG 60021(T)).

Flavobacterium ponti sp. nov., isolated from seawater

A Gram-stain-negative, non-flagellated, non-gliding, yellow-pigmented and rod-shaped bacterial strain, designated GSW-R14(T), was isolated from seawater of Geoje Island in the South Sea, Korea. Strain GSW-R14(T) grew optimally at 25 °C, at pH 7.0-8.0 and in the presence of 2u200a% (w/v) NaCl. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain GSW-R14(T) belonged to the genus Flavobacterium, joining Flavobacterium gelidilacus LMG 21477(T) by a bootstrap resampling value of 100u200a%. Strain GSW-R14(T) exhibited 97.6u200a% 16S rRNA gene sequence similarity to F. gelidilacus LMG 21477(T) and similarities of 91.2-95.2u200a% to other members of the genus Flavobacterium. Strain GSW-R14(T) contained MK-6 as the predominant menaquinone. The fatty acid profile of strain GSW-R14(T) was similar to that of F. gelidilacus LMG 21477(T). The DNA G+C content of strain GSW-R14(T) was 31.4 mol% and its DNA-DNA relatedness with F. gelidilacus LMG 21477(T) was 31u200a%. Strain GSW-R14(T) could be distinguished from F. gelidilacus and the other species of the genus Flavobacterium by its phylogenetic and genetic distinctiveness and by several phenotypic properties. On the basis of these data, strain GSW-R14(T) is considered to represent a novel species of the genus Flavobacterium, for which the name Flavobacterium ponti sp. nov. is proposed; the type strain is GSW-R14(T) (=KCTC 22802(T) =CCUG 58402(T)).

Thalassomonas agariperforans sp. nov., an agarolytic bacterium isolated from marine sand.

A Gram-staining-negative, motile, agarolytic bacterium, designated M-M1(T), was isolated from marine sand obtained from Geoje Island, South Sea, Korea, and its taxonomic position was investigated using a polyphasic taxonomic approach. Strain M-M1(T) grew optimally at pH 7.0-8.0, at 30 °C and in the presence of 2 % (w/v) NaCl. It did not grow in the presence of >7 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain M-M1(T) fell within the clade comprising members of the genus Thalassomonas, clustering with Thalassomonas agarivorans TMA1(T), Thalassomonas loyana CBMAI 722(T) and Thalassomonas ganghwensis JC2041(T), with which it exhibited 16S rRNA gene sequence similarity values of 96.4, 96.0 and 94.9 % respectively. Strain M-M1(T) exhibited 94.7-95.2 % 16S rRNA gene sequence similarity to the other species of the genus Thalassomonas. Strain M-M1(T) contained Q-8 as the predominant ubiquinone and C(16 : 1)ω7c and/or iso-C(15 : 0) 2-OH, C(16 : 0) and C(18 : 1)ω7c as the major fatty acids. The DNA G+C content was 44.2 mol%. Strain M-M1(T) could be differentiated from phylogenetically related species of the genus Thalassomonas by differences in some phenotypic properties. On the basis of the phenotypic, chemotaxonomic and phylogenetic data, strain M-M1(T) is considered to represent a novel species of the genus Thalassomonas, for which the name Thalassomonas agariperforans sp. nov. is proposed. The type strain is M-M1(T) (= KCTC 23343(T) = CCUG 60020(T)).

Algoriphagus lutimaris sp. nov., isolated from a tidal flat sediment.

A Gram-negative, non-motile, non-spore-forming bacterial strain, S1-3(T), was isolated from a tidal flat sediment on the west coast of Korea and its taxonomic position was investigated. Strain S1-3(T) grew optimally at 30 degrees C and in the presence of 2 % (w/v) NaCl. Strain S1-3(T) contained MK-7 as the predominant menaquinone and C(16 : 1)omega7c and/or iso-C(15 : 0) 2-OH and iso-C(15 : 0) as the major fatty acids. The DNA G+C content was 41.4 mol%. Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain S1-3(T) fell within the clade comprising Algoriphagus species, clustering with Algoriphagus halophilus IMSNU 14013(T), with which it exhibited 99.6 % 16S rRNA gene sequence similarity. The 16S rRNA gene sequence similarity between strain S1-3(T) and the type strains of other Algoriphagus species was 94.0-97.1 %. Differential phenotypic properties and phylogenetic and genetic distinctiveness of strain S1-3(T) demonstrated that this strain is distinguishable from the other Algoriphagus species as well as A. halophilus. On the basis of phenotypic, chemotaxonomic, phylogenetic and genetic data, strain S1-3(T) is considered to represent a novel species of the genus Algoriphagus, for which the name Algoriphagus lutimaris sp. nov. is proposed. The type strain is S1-3(T) (=KCTC 22630(T) =CCUG 57608(T)).