Development of an anti-tauopathy mucosal vaccine specifically targeting pathologic conformers.

Alzheimer's disease (AD) and related tauopathies are associated with pathological tau protein aggregation, which plays an important role in neurofibrillary degeneration and dementia. Targeted immunotherapy to eliminate pathological tau aggregates is known to improve cognitive deficits in AD animal models. The tau repeat domain (TauRD) plays a pivotal role in tau-microtubule interactions and is critically involved in the aggregation of hyperphosphorylated tau proteins. Because TauRD forms the structural core of tau aggregates, the development of immunotherapies that selectively target TauRD-induced pathological aggregates holds great promise for the modulation of tauopathies. In this study, we generated recombinant TauRD polypeptide that form neurofibrillary tangle-like structures and evaluated TauRD-specific immune responses following intranasal immunization in combination with the mucosal adjuvant FlaB. In BALB/C mice, repeated immunizations at one-week intervals induced robust TauRD-specific antibody responses in a TLR5-dependent manner. Notably, the resulting antiserum recognized only the aggregated form of TauRD, while ignoring monomeric TauRD. The antiserum effectively inhibited TauRD filament formation and promoted the phagocytic degradation of TauRD aggregate fragments by microglia. The antiserum also specifically recognized pathological tau conformers in the human AD brain. Based on these results, we engineered a built-in flagellin-adjuvanted TauRD (FlaB-TauRD) vaccine and tested its efficacy in a P301S transgenic mouse model. Mucosal immunization with FlaB-TauRD improved quality of life, as indicated by the amelioration of memory deficits, and alleviated tauopathy progression. Notably, the survival of the vaccinated mice was dramatically extended. In conclusion, we developed a mucosal vaccine that exclusively targets pathological tau conformers and prevents disease progression.

Lactococcus kimchii sp. nov., a new lactic acid bacterium isolated from kimchi.

A coccus strain designated S-13T was isolated from commercial baechu-kimchi in Korea. Comparison of the 16S rRNA gene sequence indicated that strain S-13T had the highest similarity to Lactococcus taiwanensis 0905C15T (97.9 %), Lactococcus lactis subsp. tructae L105T (97.6 %), Lactococcus lactis subsp. cremoris NCDO 607T (97.5 %), Lactococcus lactis subsp. hordniae NBRC 100931T (97.2 %), and Lactococcus lactis subsp. lactis JCM 5805T (97.2 %). The detailed phylogenetic analyses based on the 16S rRNA, rpoB and recA genes indicated that S-13T was separated from the other species and subspecies in the genus Lactococcus. The DNA-DNA relatedness between S-13T and closely related type strains, such as L. taiwanensis 0905C15T, L. lactis subsp. tructae L105T, L. lactis subsp. cremoris NCDO 607T, L. lactis subsp. hordniae NBRC 100931T, and L. lactis subsp. lactis JCM 5805T was 25.6, 20.4, 25.1, 20.2 and 21.7 %, respectively. The major fatty acids were C16 : 0, cyclo-C19 : 0ω8c and C 14 : 0. The DNA G+C content of S-13T was 39.4 mol%. From the results of the phenotypic characteristics and chemotaxonomic analysis, it was concluded that strain S-13T represents a novel species in the genus Lactococcus for which the name Lactococcus kimchii sp. nov. (=KCTC 21096T=NBRC 113348T) is proposed.

Cohnella abietis sp. nov., isolated from Korean fir (Abies koreana) rhizospheric soil of Halla mountain.

A strictly aerobic, motile, endospore-forming, rod-shaped bacterium, designated HS21T, was isolated from rhizospheric soil of the Korean fir tree (Abies koreana) from Halla mountain on Jeju island, Korea. Growth of strain HS21T was observed at pH 6.0-8.0 (optimum: pH 7.0), 0-2% (w/v) NaCl and 4-30°C (optimum: 25°C). A comparative analysis of 16S rRNA gene sequences showed that strain HS21T was most closely related to Cohnella luojiensis HY-22RT (97.6%), followed by C. lupini RLAHU4BT (97.4%) and C. collisoli NKM-5T (97.2%). The genome of strain HS21T comprised a circular chromosome of 7,059,027 bp with 44.8% G + C content. The DNA-DNA relatedness values between strain HS21T and C. luojiensis HY-22RT and C. lupini RLAHU4BT were 18.1% and 13.8%, respectively. The major cellular fatty acids (> 5%) of the isolate were anteiso-C15:0, iso-C16:0, C16:0, and iso-C15:0. The polar lipids present were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, lysylphosphatidylglycerol, and three unidentified aminophospholipids. Based on its phenotypic, phylogenetic, genomic, and chemotaxonomic properties, strain HS21T represents a novel species of the genus Cohnella, for which the name Cohnella abietis sp. nov. is proposed. The type strain is HS21T (= KCTC 43028T = CCTCC AB 2019010T).

Sulfitobacter aestuarii sp. nov., a marine bacterium isolated from a tidal flat of the Yellow Sea.

A novel bacterial strain, designated hydD52T, was isolated from a sample of tidal flat sediment of the Yellow Sea in the Republic of Korea. The cells were motile, rod-shaped and Gram-stain-negative. Phylogenetic analysis based on the 16S rRNA gene sequences revealed that strain hydD52T was a member of the genus Sulfitobacter and most closely related to Sulfitobacter dubius DSM 16472T (98.0 %), Sulfitobacter indolifex HEL-45T (97.8 %) and Sulfitobacter delicatus DSM 28223T (97.6 %). The major fatty acids (>5 %) of hydD52T were C18 : 1ω7c/C18 : 1ω6c, C16 : 0, C18 : 1ω7c 11-methyl and C19 : 0ω8c. The respiratory quinone of strain hydD52T was ubiquinone-10. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine and an unidentified amino lipid. The G+C content of this strain was 64.0 mol%. The DNA-DNA relatedness values of hydD52T with the type strains of S. dubius, S. indolifex and S. delicatus were 18.8, 13.1 and 15.7 %, respectively. Based on the results of morphological, physiological and chemotaxonomic characterization, DNA-DNA hybridization relatedness, and 16S rRNA genes analysis, we concluded that strain hydD52T represents a novel species, for which the name Sulfitobacter aestuarii sp. nov. is proposed. The type strain is hydD52T (=KCTC 32982T=TISTR 2562T).

Psychrosphaera aquimarina sp. nov., a marine bacterium isolated from seawater collected from Asan Bay, Republic of Korea.

Cells of strain SW33T, isolated from the seawater of Asan Bay, Republic of Korea, were characterized as Gram-stain-negative, aerobic, rod-shaped, motile and non-spore-forming. Phylogenetic analysis revealed that strain SW33T belonged to the genus Psychrosphaera and clustered distantly with the other genera in the family Pseudoalteromonadaceae in the phylogenetic tree. The 16S rRNA sequences of strain SW33T revealed high similarities to Psychrosphaera saromensis SA4-48T (98.7 %), Psychrosphaera haliotis KDW4T (97.4 %) and Psychrosphaera aestuarii PSC101T (97.3 %). The major fatty acids were C16 : 0 (27.9 %), summed feature 3 (32.2 %) and summed feature 8 (17.2 %). The predominant quinone was Q-8, and the polar lipid profile consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and an unidentified amino lipid. The DNA G+C content was 38.3 mol%. The DNA-DNA relatedness values with the three species of Psychrosphaera saromensis KCTC 23240T, Psychrosphaera haliotis KCTC 22500T and Psychrosphaera aestuarii KCTC 32274T were 22, 23 and 18 %, respectively. Based on the phenotypic characteristics and taxonomic analyses, we propose that strain SW33T represents a novel species within the genus Psychrosphaera, for which the name Psychrosphaera aquimarina sp. nov. with the type strain SW33T (=KCTC 52743T=CICC 24249T) is proposed.

Paucibacter oligotrophus sp. nov., isolated from fresh water, and emended description of the genus Paucibacter.

A Gram-stain-negative, rod-shaped, non-spore forming, motile and strictly oxidative bacterium, strain CHU3T, was isolated from fresh water in the Daecheong Reservoir, South Korea. A comparison of the 16S rRNA gene sequence showed that the novel bacterium is closely related to Paucibacter toxinivorans 2C20T (=KCTC 42569T) with a sequence similarity value of 97.8 %, Pelomonas saccharophila DSM 654T (=KCTC 52256T) with 97.4 % similarity and Pelomonas aquatica CCUG 52575T (=KCTC 42961T) with 97.3 % similarity, respectively. The major fatty acids (>10 %) of the isolate were summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and C16 : 0. Ubiquinone-8 was detected as the respiratory quinone. The polar lipids contained diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylserine and an unidentified aminolipid. The DNA G+C content was 62.5 mol%. DNA-DNA hybridization experiments with PaucibactertoxinivoransKCTC 42569T (=2C20T), PelomonassaccharophilaKCTC 52256T (=DSM 654T) and PelomonasaquaticaKCTC 42961T (=CCUG 52575T) resulted in relatedness values of 20 % (reciprocal 11 %), 16 % (reciprocal 17 %) and 15 % (reciprocal 19 %), respectively. The phylogenetic analysis, DNA-DNA hybridization value, polar lipids, fatty acid composition and other physiological characteristics confirmed that strain CHU3T represents a novel species in the genus Paucibacter for which the name Paucibacter oligotrophus sp. nov. is proposed. The type strain is CHU3T (=KCTC 42519T=CICC 24092T). An emended description of the genus Paucibacter is also proposed on the basis of new data obtained in this study.

Agarivorans aestuarii sp. nov., an agar-degrading bacterium isolated from a tidal flat.

A Gram-reaction-negative, aerobic, non-spore forming, rod-shaped bacterium motile with a single polar flagellum, designated strain hydD622T, was isolated from the sediment of a tidal flat at Asan Bay, Korea. Strain hydD622T exhibited an agarolytic activity. Comparison of 16S rRNA gene sequences revealed that strain hydD622T was closely related to Agarivorans litoreus KCTC 42116T, Agarivorans albus KCTC 22256T and Agarivorans gilvus KCTC 32555T with similarities of 98.4, 98.0 and 96.5 %, respectively. Strain hydD622T was clustered distantly from the other genera in the family Alteromonadaceae but formed a unique clade within the genus Agarivorans based on the 16S rRNA gene sequence. The DNA-DNA relatedness with Agarivorans litoreus KCTC 42116T and Agarivorans. albus KCTC 22256T was 39.0 and 37.8 %, respectively. The major fatty acids (>10 %) were C16 : 0,C16 : 1ω6c/C16 : 1ω7c and C18 : 1ω6c/C18 : 1ω7c. The respiratory quinone was ubiquinone-8, and the polar lipid profile consisted of phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol and an unidentified lipid. The DNA G+C content was 44 mol%. On the basis of physiological, chemotaxonomic and phylogenetic analyses, strain hydD622T represents a novel species within the genus Agarivorans, for which the name Agarivorans aestuarii sp. nov. is proposed. The type strain of Agarivorans aestuarii sp. nov. is hydD622T (=KCTC 32543T=CGMCC 1.12692T).

Flavobacterium tistrianum sp. nov., a gliding bacterium isolated from soil.

A novel gliding bacterial strain, GB 56.1T, was obtained from soil at the Sakaerat Biosphere Reserve, in Nakhon Ratchasima province, Thailand; the strain was characterized using a polyphasic approach. Cells were Gram-stain-negative, yellow, rod shaped and devoid of flagella, but showed gliding motility. Phylogenetic analysis based on 16S rRNA gene sequences found that GB 56.1T was a member of the genus Flavobacterium and that the strain shared the highest sequence similarities with Flavobacterium nitrogenifigens (98.4 %), Flavobacterium anhuiense(98.3 %) and Flavobacterium ginsenosidimutans (97.9 %). The similarities of the sequences of all other species of the genus Flavobacterium were below 97.4 %. The major respiratory quinone of strain GB 56.1T was MK-6; fatty acids were iso-C15:0, C16:1ω6c/C16:1ω7c, C16:0 and C16:0 3-OH. The major polar lipids were phosphatidylethanolamine, phosphatidylserine, an unidentified amino lipid and four polar lipids. The DNA G+C content of this strain was 34.2 mol%. The DNA-DNA relatedness of GB 56.1T was highest against F.anhuiense, with a value of 37.6 %. On the basis of morphological, physiological and chemotaxonomic characteristics, DNA-DNA hybridization relatedness and 16S rRNA gene sequence analysis, we conclude that strain GB 56.1T represents a novel species, for which the name Flavobacterium tistrianum sp. nov. is proposed. The type strain is GB 56.1T (=TISTR 1612T =KCTC 42679T).