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Papers - YAMAMOTO Sou

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乳酸桿菌の対数期に膜小胞上に局在するリポテイコ酸

白石宗, 横田伸一, 佐藤耶舞羽, 伊藤利章, 吹谷智, 山本聡, 佐藤豊孝, 横田篤

日本乳酸菌学会誌 ( 日本乳酸菌学会 ) 29 ( 2 ) 116 - 116 2018.07

Autophagy Differentially Regulates Insulin Production and Insulin Sensitivity.

Soh Yamamoto, Kenta Kuramoto, Nan Wang, Xiaolei Situ, Medha Priyadarshini, Weiran Zhang, Jose Cordoba-Chacon, Brian T Layden, Congcong He

Cell reports ( Elsevier B.V. ) 23 ( 11 ) 3286 - 3299 2018.06 [Refereed] [International journal]

Authorship： Lead author

Autophagy, a stress-induced lysosomal degradative pathway, has been assumed to exert similar metabolic effects in different organs. Here, we establish a model where autophagy plays different roles in insulin-producing β cells versus insulin-responsive cells, utilizing knockin (Becn1F121A) mice manifesting constitutively active autophagy. With a high-fat-diet challenge, the autophagy-hyperactive mice unexpectedly show impaired glucose tolerance, but improved insulin sensitivity, compared to mice with normal autophagy. Autophagy hyperactivation enhances insulin signaling, via suppressing ER stress in insulin-responsive cells, but decreases insulin secretion by selectively sequestrating and degrading insulin granule vesicles in β cells, a process we term "vesicophagy." The reduction in insulin storage, insulin secretion, and glucose tolerance is reversed by transient treatment of autophagy inhibitors. Thus, β cells and insulin-responsive tissues require different autophagy levels for optimal function. To improve insulin sensitivity without hampering secretion, acute or intermittent, rather than chronic, activation of autophagy should be considered in diabetic therapy development.

DOI PubMed

Release of large amounts of lipopolysaccharides from Pseudomonas aeruginosa cells reduces their susceptibility to colistin.

Shin-Ichi Yokota, Hiroshi Hakamada, Soh Yamamoto, Toyotaka Sato, Tsukasa Shiraishi, Masaaki Shinagawa, Satoshi Takahashi

International journal of antimicrobial agents 51 ( 6 ) 888 - 896 2018.06 [Refereed] [International journal]

Pseudomonas aeruginosa is an important etiological agent of opportunistic infections. Injectable colistin is available as a last-line treatment option for multidrug-resistant P. aeruginosa infections. When cells were inoculated at a high number, colistin-susceptible P. aeruginosa grew on agar medium containing colistin at a concentration 10-fold higher than the minimum inhibitory concentration without acquiring colistin resistance. This study examined the responsible mechanism for growth in the presence of a high concentration of colistin. Cell wash fluid derived from P. aeruginosa efficiently reduced colistin antimicrobial activity. This reduction was mediated by lipopolysaccharide (LPS) in the wash fluid. Extracellular LPS inhibited colistin activity more effectively than cell-bound LPS in fixed cells. Cell wash fluids from Escherichia coli and Acinetobacter baumannii also reduced colistin activity; however, they were less potent than those from P. aeruginosa. The amount of LPS in cell wash fluid from P. aeruginosa was approximately 10-fold higher than that in fluid from E. coli or A. baumannii. In conclusion, cell-free LPS derived from bacterial cells inhibited the antimicrobial activity of colistin, and this effect was greatest for P. aeruginosa. Thus, large amounts of broken and dead cells of P. aeruginosa at infection foci will reduce the effectiveness of colistin, even against cells that have not yet acquired resistance.

DOI PubMed

Evaluation of consistency in quantification of gene copy number by real-time reverse transcription quantitative polymerase chain reaction and virus titer by plaque-forming assay for human respiratory syncytial virus.

Keisuke Yamamoto, Noriko Ogasawara, Soh Yamamoto, Kenichi Takano, Tsukasa Shiraishi, Toyotaka Sato, Hiroyuki Tsutsumi, Tetsuo Himi, Shin-Ichi Yokota

Microbiology and immunology 62 ( 2 ) 90 - 98 2018.02 [Refereed] [International journal]

The plaque-forming assay is the standard technique for determining viral titer, and a critical measurement for investigating viral replication. However, this assay is highly dependent on experimental technique and conditions. In the case of human respiratory syncytial virus (RSV) in particular, it can be difficult to objectively confirm the accuracy of plaque-forming assay because the plaques made by RSV are often small and unclear. In recent studies, RT-qPCR methods have emerged as a supportive procedure for assessment of viral titer, yielding highly sensitive and reproducible results. In this report, we compare the viral replication, as determined by plaque-forming assay, and the copy numbers of RSV genes NS1, NS2, N, and F, as determined by RT-qPCR. Two real-time PCR systems, SYBR Green and TaqMan probe, gave highly similar results for measurement of copy numbers of RSV N genes of virus subgroups A. We determined the RSV gene copy numbers in the culture cell supernatant and cell lysate measured at various multiplicities of infection. We found that copy number of the RSV N gene in the culture supernatant and cell lysate was highly correlated with plaque-forming units. In conclusion, RT-qPCR measurement of RSV gene copy number was highly dependent on viral titer, and the detailed comparison between each gene copy number and virus titer should be useful and supportive in confirming RSV plaque-forming assay and virus dynamics. The technique may also be used to estimate the amount of RSV present in clinical specimens.

DOI PubMed

Lipoteichoic acids are embedded in cell walls during logarithmic phase, but exposed on membrane vesicles in Lactobacillus gasseri JCM 1131T

Shiraishi T, Yokota, S, Sato Y, Ito T, Fukiya S, Yamamoto S, Sato T, Yokota A

Beneficial Microbes 9 ( 4 ) 653 - 662 2018 [Refereed]

Novel antimicrobial activities of a peptide derived from a Japanese soybean fermented food, Natto, against Streptococcus pneumoniae and Bacillus subtilis group strains.

Manabu Kitagawa, Tsukasa Shiraishi, Soh Yamamoto, Ryosuke Kutomi, Yasuo Ohkoshi, Toyotaka Sato, Hideki Wakui, Hideaki Itoh, Atsushi Miyamoto, Shin-Ichi Yokota

AMB Express ( BIOMED CENTRAL LTD ) 7 ( 1 ) 127 - 127 2017.12 [Refereed] [International journal]

We recently isolated a tumoricidal peptide from Natto, a Japanese traditional fermented food. In the present study, antimicrobial activity of the Natto peptide was examined. The peptide consisted of 45 amino acid residues, and its structure was predicted to be rich in α-helix. It excreted antimicrobial activity only against Streptococcus pneumoniae and Bacillus subtilis group (B. subtilis, Bacillus pumilus, and Bacillus licheniformis). Lesser antimicrobial activity was observed for Streptococcus species other than S. pneumoniae. Hemolysate or hemin was required for the antimicrobial activity of the peptide. The Natto peptide damages the cell membrane of B. subtilis. On the other hand, chain morphology was induced in S. pneumoniae, which is naturally diplococcus, during the early phases of the Natto peptide treatment; following that the cells were rapidly lysed. This suggested that the Natto peptide displayed a novel narrow spectrum of bactericidal activity and inhibited cell separation during cell division of S. pneumoniae.

DOI PubMed

A Becn1 mutation mediates hyperactive autophagic sequestration of amyloid oligomers and improved cognition in Alzheimer's disease.

Altea Rocchi, Soh Yamamoto, Tabitha Ting, Yuying Fan, Katherine Sadleir, Yigang Wang, Weiran Zhang, Sui Huang, Beth Levine, Robert Vassar, Congcong He

PLoS genetics ( Public Library of Science ) 13 ( 8 ) e1006962 2017.08 [Refereed] [International journal]

Impairment of the autophagy pathway has been observed during the pathogenesis of Alzheimer's disease (AD), a neurodegenerative disorder characterized by abnormal deposition of extracellular and intracellular amyloid β (Aβ) peptides. Yet the role of autophagy in Aβ production and AD progression is complex. To study whether increased basal autophagy plays a beneficial role in Aβ clearance and cognitive improvement, we developed a novel genetic model to hyperactivate autophagy in vivo. We found that knock-in of a point mutation F121A in the essential autophagy gene Beclin 1/Becn1 in mice significantly reduces the interaction of BECN1 with its inhibitor BCL2, and thus leads to constitutively active autophagy even under non-autophagy-inducing conditions in multiple tissues, including brain. Becn1F121A-mediated autophagy hyperactivation significantly decreases amyloid accumulation, prevents cognitive decline, and restores survival in AD mouse models. Using an immunoisolation method, we found biochemically that Aβ oligomers are autophagic substrates and sequestered inside autophagosomes in the brain of autophagy-hyperactive AD mice. In addition to genetic activation of autophagy by Becn1 gain-of-function, we also found that ML246, a small-molecule autophagy inducer, as well as voluntary exercise, a physiological autophagy inducer, exert similar Becn1-dependent protective effects on Aβ removal and memory in AD mice. Taken together, these results demonstrate that genetically disrupting BECN1-BCL2 binding hyperactivates autophagy in vivo, which sequestrates amyloid oligomers and prevents AD progression. The study establishes new approaches to activate autophagy in the brain, and reveals the important function of Becn1-mediated autophagy hyperactivation in the prevention of AD.

DOI PubMed

マクロライド作用機序クラリスロマイシンの炎症反応修飾作用の分子機構の解明気道上皮細胞のクラリスロマイシン結合タンパク質の同定と機能解析

横田伸一, 山本聡, 小笠原徳子, 植村知加, 高谷芳明, 伊藤英晃, 山本圭佑, 白石宗, 佐藤豊孝, 氷見徹夫

The Japanese Journal of Antibiotics ( (公財)日本感染症医薬品協会 ) 70 ( Suppl.A ) 60 - 64 2017.03

ウイルス、細菌、真菌クラリスロマイシンは気道上皮細胞でRSウイルスによって誘導されるインターフェロンの産生をIRF-3を介して調整する

山本圭佑, 小笠原徳子, 山本聡, 堤裕幸, 氷見徹夫, 横田伸一

The Japanese Journal of Antibiotics ( (公財)日本感染症医薬品協会 ) 70 ( Suppl.A ) 19 - 24 2017.03

患者の手術で採取した鼻粘膜から作製したhTERT導入鼻粘膜上皮細胞(hTERT-HNEC)、肺胞上皮由来細胞株(A549)、ヒト気道上皮細胞株(BEAS-2B)を用い、ヒト気道上皮細胞における急性呼吸器ウイルス感染症に対するクラリスロマイシン(CAM)の効果と、CAMのもつ免疫調節効果のメカニズムを調べるため各種検討した。RSウイルス(RSV)感染のCAMの影響を調べ、CAMがRSV増殖に影響を与えないことが示唆された。hTERT-HNEC、A549、BEAS-2Bなどの気道上皮細胞においてPoly:C処置、RSV感染で誘導されるIFN-β、IFN-λがCAMにより強く抑制された。宿主の自然免疫に関わる転写因子IRF、NF-κB、AP-1の結合領域を含むプロモーター活性化がCAMにより強く抑制された。

NIP-SNAP-1 and -2 mitochondrial proteins are maintained by heat shock protein 60.

Soh Yamamoto, Tomoya Okamoto, Noriko Ogasawara, Shin Hashimoto, Tsukasa Shiraishi, Toyotaka Sato, Keisuke Yamamoto, Hiroyuki Tsutsumi, Kenichi Takano, Testuo Himi, Hideaki Itoh, Shin-Ichi Yokota

Biochemical and biophysical research communications ( ACADEMIC PRESS INC ELSEVIER SCIENCE ) 483 ( 3 ) 917 - 922 2017.02 [Refereed] [International journal]

Authorship： Lead author

NIP-SNAP-1 and -2 are ubiquitous proteins thought to be associated with maintenance of mitochondrial function, neuronal transmission, and autophagy. However, their physiological functions remain largely unknown. To elucidate their functional importance, we screened for proteins that interact with NIP-SNAP-1 and -2, resulting in identification of HSP60 and P62/SQSTM1 as binding proteins. NIP-SNAP-1 and -2 localized in the mitochondrial inner membrane space, whereas HSP60 localized in the matrix. Native gel electrophoresis and filter trap assays revealed that human HSP60 prevented aggregation of newly synthesized NIP-SNAP-2 in an in vitro translation system. Moreover, expression levels of NIP-SNAP-1 and -2 in cells were decreased by knockdown of HSP60, but not HSP10. These findings indicate that HSP60 promotes folding and maintains the stability of NIP-SNAP-1 and -2.

DOI PubMed

Mitochondrial proteins NIP-SNAP-1 and -2 are a target for the immunomodulatory activity of clarithromycin, which involves NF-κB-mediated cytokine production.

Soh Yamamoto, Noriko Ogasawara, Keisuke Yamamoto, Chika Uemura, Yoshiaki Takaya, Tsukasa Shiraishi, Toyotaka Sato, Shin Hashimoto, Hiroyuki Tsutsumi, Kenichi Takano, Tetsuo Himi, Shin-Ichi Yokota

Biochemical and biophysical research communications ( ACADEMIC PRESS INC ELSEVIER SCIENCE ) 483 ( 3 ) 911 - 916 2017.02 [Refereed] [International journal]

Authorship： Lead author

Macrolide antibiotics have immunomodulatory activities, including suppression of cytokine production, cell adhesion molecule expression, and mucin production. These immunomodulatory activities improve the symptoms of respiratory diseases associated with chronic inflammation. However, the underlying molecular mechanism(s) is not well understood yet. To address this, we prepared clarithromycin (CAM)-conjugated Sepharose and examined bound cellular proteins by proteome analysis. We identified mitochondrial proteins 4-nitrophenylphosphatase domain and non-neuronal synaptosomal associated protein 25-like protein homolog (NIP-SNAP)-1 and -2 and very long-chain acyl-CoA dehydrogenase (VLCAD) as CAM-binding proteins. Production of proinflammatory cytokines (IL-8 and IL-6) induced by lipopolysaccharides (LPSs) and Pam3-CSK4 in human epithelial cell lines BEAS-2B and T24 were suppressed by knockdown of NIP-SNAP-1 or -2, and partly by knockdown of VLCAD. Also, knockdown of NIP-SNAP-1 or -2 in various cell lines suppressed LPS-induced expression of IL-8 and IL-6 mRNA and NF-κB activity. Thus, CAM suppresses NF-κB-mediated proinflammatory cytokine production by interacting with mitochondrial proteins, NIP-SNAP-1 and -2.

DOI PubMed

タゾバクタム/ピペラシリン耐性大腸菌の耐性機構の解析

鈴木裕樹, 佐藤豊孝, 山本聡, 小笠原徳子, 白石宗, 品川雅明, 高橋聡, 横田伸一

日本細菌学雑誌 ( 日本細菌学会 ) 72 ( 1 ) 138 - 138 2017.02

Tigecycline Nonsusceptibility Occurs Exclusively in Fluoroquinolone-Resistant Escherichia coli Clinical Isolates, Including the Major Multidrug-Resistant Lineages O25b:H4-ST131-H30R and O1-ST648.

Toyotaka Sato, Yuuki Suzuki, Tsukasa Shiraishi, Hiroyuki Honda, Masaaki Shinagawa, Soh Yamamoto, Noriko Ogasawara, Hiroki Takahashi, Satoshi Takahashi, Yutaka Tamura, Shin-Ichi Yokota

Antimicrobial agents and chemotherapy ( AMER SOC MICROBIOLOGY ) 61 ( 2 ) 2017.02 [Refereed] [International journal]

Tigecycline (TGC) is a last-line drug for multidrug-resistant Enterobacteriaceae We investigated the mechanism(s) underlying TGC nonsusceptibility (TGC resistant/intermediate) in Escherichia coli clinical isolates. The MIC of TGC was determined for 277 fluoroquinolone-susceptible isolates (ciprofloxacin [CIP] MIC, <0.125 mg/liter) and 194 fluoroquinolone-resistant isolates (CIP MIC, >2 mg/liter). The MIC50 and MIC90 for TGC in fluoroquinolone-resistant isolates were 2-fold higher than those in fluoroquinolone-susceptible isolates (MIC50, 0.5 mg/liter versus 0.25 mg/liter; MIC90, 1 mg/liter versus 0.5 mg/liter, respectively). Two fluoroquinolone-resistant isolates (O25b:H4-ST131-H30R and O125:H37-ST48) were TGC resistant (MICs of 4 and 16 mg/liter, respectively), and four other isolates of O25b:H4-ST131-H30R and an isolate of O1-ST648 showed an intermediate interpretation (MIC, 2 mg/liter). No TGC-resistant/intermediate strains were found among the fluoroquinolone-susceptible isolates. The TGC-resistant/intermediate isolates expressed higher levels of acrA and acrB and had lower intracellular TGC concentrations than susceptible isolates, and they possessed mutations in acrR and/or marR The MICs of acrAB-deficient mutants were markedly lower (0.25 mg/liter) than those of the parental strain. After continuous stepwise exposure to CIP in vitro, six of eight TGC-susceptible isolates had reduced TGC susceptibility. Two of them acquired TGC resistance (TGC MIC, 4 mg/liter) and exhibited expression of acrA and acrB and mutations in acrR and/or marR In conclusion, a population of fluoroquinolone-resistant E. coli isolates, including major extraintestinal pathogenic lineages O25b:H4-ST131-H30R and O1-ST648, showed reduced susceptibility to TGC due to overexpression of the efflux pump AcrAB-TolC, leading to decreased intracellular concentrations of the antibiotics that may be associated with the development of fluoroquinolone resistance.

DOI PubMed

日本のダイズ発酵食品である納豆由来ペプチドの新規の抗菌活性(Novel antimicrobial activities of a peptide derived from a Japanese soy-bean fermented food, Natto)

北川学, 白石宗, 山本聡, 久富亮佑, 佐藤豊孝, 小笠原徳子, 宮本篤, 横田伸一

日本細菌学雑誌 ( 日本細菌学会 ) 72 ( 1 ) 145 - 145 2017.02

Mechanism of Reduced Susceptibility to Fosfomycin in Escherichia coli Clinical Isolates.

Yasuo Ohkoshi, Toyotaka Sato, Yuuki Suzuki, Soh Yamamoto, Tsukasa Shiraishi, Noriko Ogasawara, Shin-Ichi Yokota

BioMed research international ( HINDAWI LTD ) 2017 5470241 - 5470241 2017 [Refereed] [International journal]

In recent years, multidrug resistance of Escherichia coli has become a serious problem. However, resistance to fosfomycin (FOM) has been low. We screened E. coli clinical isolates with reduced susceptibility to FOM and characterized molecular mechanisms of resistance and reduced susceptibility of these strains. Ten strains showing reduced FOM susceptibility (MIC ≥ 8 μg/mL) in 211 clinical isolates were found and examined. Acquisition of genes encoding FOM-modifying enzyme genes (fos genes) and mutations in murA that underlie high resistance to FOM were not observed. We examined ability of FOM incorporation via glucose-6-phosphate (G6P) transporter and sn-glycerol-3-phosphate transporter. In ten strains, nine showed lack of growth on M9 minimum salt agar supplemented with G6P. Eight of the ten strains showed fluctuated induction by G6P of uhpT that encodes G6P transporter expression. Nucleotide sequences of the uhpT, uhpA, glpT, ptsI, and cyaA shared several deletions and amino acid mutations in the nine strains with lack of growth on G6P-supplemented M9 agar. In conclusion, reduction of uhpT function is largely responsible for the reduced sensitivity to FOM in clinical isolates that have not acquired FOM-modifying genes or mutations in murA. However, there are a few strains whose mechanisms of reduced susceptibility to FOM are still unclear.

DOI PubMed

Pathogenic Lineage of mcr-Negative Colistin-Resistant Escherichia coli, Japan, 2008-2015.

Toyotaka Sato, Akira Fukuda, Yuuki Suzuki, Tsukasa Shiraishi, Hiroyuki Honda, Masaaki Shinagawa, Soh Yamamoto, Noriko Ogasawara, Masaru Usui, Hiroki Takahashi, Satoshi Takahashi, Yutaka Tamura, Shin-Ichi Yokota

Emerging infectious diseases ( CENTERS DISEASE CONTROL ) 22 ( 12 ) 2223 - 2225 2016.12 [Refereed] [International journal]

DOI PubMed

Clarithromycin prevents human respiratory syncytial virus-induced airway epithelial responses by modulating activation of interferon regulatory factor-3.

Keisuke Yamamoto, Soh Yamamoto, Noriko Ogasawara, Kenichi Takano, Tsukasa Shiraishi, Toyotaka Sato, Ryo Miyata, Takuya Kakuki, Ryuta Kamekura, Takashi Kojima, Hiroyuki Tsutsumi, Tetsuo Himi, Shin-Ichi Yokota

Pharmacological research ( ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD ) 111 804 - 814 2016.09 [Refereed] [International journal]

Macrolide antibiotics exert immunomodulatory activity by reducing pro-inflammatory cytokine production by airway epithelial cells, fibroblasts, vascular endothelial cells, and immune cells. However, the underlying mechanism of action remains unclear. Here, we examined the effect of clarithromycin (CAM) on pro-inflammatory cytokine production, including interferons (IFNs), by primary human nasal epithelial cells and lung epithelial cell lines (A549 and BEAS-2B cells) after stimulation by Toll-like receptor (TLR) and RIG-I-like receptor (RLR) agonists and after infection by human respiratory syncytial virus (RSV). CAM treatment led to a significant reduction in poly I:C- and RSV-mediated IL-8, CCL5, IFN-β and -λ production. Furthermore, IFN-β promoter activity (activated by poly I:C and RSV infection) was significantly reduced after treatment with CAM. CAM also inhibited IRF-3 dimerization and subsequent translocation to the nucleus. We conclude that CAM acts a crucial modulator of the innate immune response, particularly IFN production, by modulating IRF-3 dimerization and subsequent translocation to the nucleus of airway epithelial cells. This newly identified immunomodulatory action of CAM will facilitate the discovery of new macrolides with an anti-inflammatory role.

DOI PubMed

Measles Virus Genotype D Wild Strains Suppress Interferon-Stimulated Gene Expression More Potently than Laboratory Strains in SiHa Cells.

Masaru Jinushi, Soh Yamamoto, Noriko Ogasawara, Hideki Nagano, Shin Hashimoto, Hiroyuki Tsutsumi, Tetsuo Himi, Shin-Ichi Yokota

Viral immunology ( MARY ANN LIEBERT, INC ) 29 ( 5 ) 296 - 306 2016.06 [Refereed] [International journal]

Changes in interferon (IFN)-stimulated gene (ISG) expression in cells infected with measles virus (MeV), four wild strains (belonging to different genotypes), and the laboratory strain Edmonston were examined. ISGs [MxA, 2'-5'-oligoadenylate synthetase, and interferon regulatory factor-1] were upregulated in an MeV-infection-induced manner and in an IFN-induced manner. In MeV-infected SiHa cell lines, the MeV infection-induced expression levels were in the order of A>H1>D8>D5>D3. On the other hand, all infected cell lines abolished type I and III IFN-induced ISG expression. However, partial type II IFN-mediated induction was observed in the MeV-infected cells. The wild strain of genotype D3 was the most potent inhibitor of MeV infection-induced and IFN-induced ISG expression and generated the highest titer of infectious viral particles. Edmonston triggered the highest levels of MeV infection-induced ISG expression in SiHa cells and produced the lowest titer of infectious particles. Expression of the viral C protein was associated with suppression of MeV infection-induced and type II IFN-induced ISG expression.

DOI PubMed

Mumps Virus Induces Protein-Kinase-R-Dependent Stress Granules, Partly Suppressing Type III Interferon Production.

Shin Hashimoto, Soh Yamamoto, Noriko Ogasawara, Toyotaka Sato, Keisuke Yamamoto, Hiroshi Katoh, Toru Kubota, Tsukasa Shiraishi, Takashi Kojima, Tetsuo Himi, Hiroyuki Tsutsumi, Shin-Ichi Yokota

PloS one ( PUBLIC LIBRARY SCIENCE ) 11 ( 8 ) e0161793 2016 [Refereed] [International journal]

Authorship： Corresponding author

Stress granules (SGs) are cytoplasmic granular aggregations that are induced by cellular stress, including viral infection. SGs have opposing antiviral and proviral roles, which depend on virus species. The exact function of SGs during viral infection is not fully understood. Here, we showed that mumps virus (MuV) induced SGs depending on activation of protein kinase R (PKR). MuV infection strongly induced interferon (IFN)-λ1, 2 and 3, and IFN-β through activation of IFN regulatory factor 3 (IRF3) via retinoic acid inducible gene-I (RIG-I) and the mitochondrial antiviral signaling (MAVS) pathway. MuV-induced IFNs were strongly upregulated in PKR-knockdown cells. MuV-induced SG formation was suppressed by knockdown of PKR and SG marker proteins, Ras-GTPase-activating protein SH3-domain-binding protein 1 and T-cell-restricted intracellular antigen-1, and significantly increased the levels of MuV-induced IFN-λ1. However, viral titer was not altered by suppression of SG formation. PKR was required for induction of SGs by MuV infection and regulated type III IFN (IFN-λ1) mRNA stability. MuV-induced SGs partly suppressed type III IFN production by MuV; however, the limited suppression was not sufficient to inhibit MuV replication in cell culture. Our results provide insight into the relationship between SGs and IFN production induced by MuV infection.

DOI PubMed

Intrafamilial, Preferentially Mother-to-Child and Intraspousal, Helicobacter pylori Infection in Japan Determined by Mutilocus Sequence Typing and Random Amplified Polymorphic DNA Fingerprinting.

Shin-ichi Yokota, Mutsuko Konno, Shin-ichi Fujiwara, Nariaki Toita, Michiko Takahashi, Soh Yamamoto, Noriko Ogasawara, Tsukasa Shiraishi

Helicobacter ( WILEY-BLACKWELL ) 20 ( 5 ) 334 - 42 2015.10 [Refereed] [International journal]

BACKGROUND: The infection route of Helicobacter pylori has been recognized to be mainly intrafamilial, preferentially mother-to-child, especially in developed countries. To determine the transmission route, we examined whether multilocus sequence typing (MLST) was useful for analysis of intrafamilial infection. The possibility of intraspousal infection was also evaluated. MATERIALS AND METHODS: Clonal relationships between strains derived from 35 index Japanese pediatric patients, and their family members were analyzed by two genetic typing procedures, MLST and random amplified polymorphic DNA (RAPD) fingerprinting. RESULTS: Mostly coincident results were obtained by MLST and RAPD. By MLST, the allele of loci in the isolates mostly matched between the index child and both the father and mother for 9 (25.7%) of the 35 patients, between the index child and the mother for 25 (60.0%) of the 35 patients. CONCLUSIONS: MLST is useful for analyzing the infection route of H. pylori as a highly reproducible method. Intrafamilial, especially mother-to-children and sibling, infection is the dominant transmission route. Intraspousal infection is also thought to occur in about a quarter in the Japanese families.

DOI PubMed

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Papers - YAMAMOTO Sou