Researchers Database

watanabe shinya

    DepartmentofInfectionandImmunityDivisionofBacteriology Associate Professor
Last Updated :2021/12/07

Researcher Information

URL

J-Global ID

Research Interests

  • 細菌学   感染症   

Research Areas

  • Life sciences / Bacteriology

Academic & Professional Experience

  • 2018/11 - Today  Jichi Medical Univ.Division of Bacteriology, Department of Infection and Immunity, School of MedicineAssociate Professor
  • 2015/04 - 2018/10  Jichi Medical Univ.Division of Bacteriology, Department of Infection and Immunity, School of MedicineLecturer
  • 2011/04 - 2015/03  NCGMDepartment of Infectious DiseasesSenior Researcher
  • 2008/05 - 2011/03  NIAID/NIHTuberculosis Research SectionVisiting Fellow
  • 2008/04 - 2008/05  Juntendo UniversityDepartment of Infection Control SciencePostdoctroal Fellow

Association Memberships

  • THE MOLECULAR BIOLOGY SOCIETY OF JAPAN   American Society for Microbiology   JAPANESE SOCIETY FOR BACTERIOLOGY   

Published Papers

  • Katsuyuki Katahira, Shinya Watanabe, Kentaro Wakamatsu, Zenzo Nagasawa, Masayuki Kawasaki, Longzhu Cui
    Microbiology Resource Announcements 10 (27) 2021/07 [Refereed]
     
    We report the complete genome sequence of Mycobacterium heckeshornense strain JMUB5695, which was isolated from necrotizing granulomatous lesions in a lung cancer patient. The complete genome consists of a 4,865,109-bp chromosome with a GC content of 65.9% and contains no plasmids.
  • Pourya Gholizadeh, Mohammad Aghazadeh, Reza Ghotaslou, Mohammad Ahangarzadeh Rezaee, Tahereh Pirzadeh, Longzhu Cui, Shinya Watanabe, Hadi Feizi, Hiva Kadkhoda, Hossein Samadi Kafil
    Annals of Clinical Microbiology and Antimicrobials 20 (1) 2021/07 [Refereed]
     
    AbstractClustered regularly interspaced short palindromic repeat (CRISPR)-Cas systems are one of the factors which can contribute to limiting the development and evolution of antibiotic resistance in bacteria. There are three genomic loci of CRISPR-Cas in Enterococcus faecalis. In this study, we aimed to assess correlation of the CRISPR-Cas system distribution with the acquisition of antibiotic resistance among E. faecalis isolates. A total of 151 isolates of E. faecalis were collected from urinary tract infections (UTI) and dental-root canal (DRC). All isolates were screened for phenotypic antibiotic resistance. In addition, antibiotic resistance genes and CRISPR loci were screened by using polymerase chain reaction. Genomic background of the isolates was identified by random amplified polymorphic DNA (RAPD)-PCR. The number of multidrug-resistant E. faecalis strains were higher in UTI isolates than in DRC isolates. RAPD-PCR confirmed that genomic background was diverse in UTI and DRC isolates used in this study. CRISPR loci were highly accumulated in gentamycin-, teicoplanin-, erythromycin-, and tetracycline-susceptible strains. In concordance with drug susceptibility, smaller number of CRISPR loci were identified in vanA, tetM, ermB, aac6’-aph(2”), aadE, and ant(6) positive strains. These data indicate a negative correlation between CRISPR-cas loci and antibiotic resistance, as well as, carriage of antibiotic resistant genes in both of UTI and DRC isolates.
  • Ahmed Tabbabi, Shinya Watanabe, Daiki Mizushima, Abraham G. Caceres, Eduardo A Gomez, Daisuke S. Yamamoto, Longzhu Cui, Yoshihisa Hashiguchi, Hirotomo Kato
    Microorganisms 9 (1) 68 - 68 2021/01 [Refereed]
     
    Differences in the gut microbial content of Lutzomyia (Lu.) ayacuchensis, a primary vector of Andean-type cutaneous leishmaniasis in Ecuador and Peru, may influence the susceptibility of these sand flies to infection by Leishmania. As a first step toward addressing this hypothesis, a comparative analysis of bacterial and fungal compositions from Lu. ayacuchensis populations with differential susceptibilities to Leishmania was performed. Bacterial 16S rRNA gene amplification and Illumina MiSeq sequencing approaches were used to characterize the bacterial composition in wild-caught populations from the Andean areas of Ecuador and southern Peru at which the sand fly species transmit Leishmania (Leishmania) mexicana and Leishmania (Viannia) peruviana, respectively, and a population from the northern Peruvian Andes at which the transmission of Leishmania by Lu. ayacuchensis has not been reported. In the present study, 59 genera were identified, 21 of which were widely identified and comprised more than 95% of all bacteria. Of the 21 dominant bacterial genera identified in the sand flies collected, 10 genera had never been detected in field sand flies. The Ecuador and southern Peru populations each comprised individuals of particular genera, while overlap was clearly observed between microbes isolated from different sites, such as the number of soil organisms. Similarly, Corynebacterium and Micrococcus were slightly more dominant bacterial genera in the southern Peru population, while Ochrobactrum was the most frequently isolated from other populations. On the other hand, fungi were only found in the southern Peru population and dominated by the Papiliotrema genus. These results suggest that variation in the insect gut microbiota may be elucidated by the ecological diversity of sand flies in Peru and Ecuador, which may influence susceptibility to Leishmania infection. The present study provides key insights for understanding the role of the microbiota during the course of L. (L.) mexicana and L. (V.) peruviana infections in this important vector.
  • Tanit Boonsiri, Shinya Watanabe, Xin-Ee Tan, Kanate Thitiananpakorn, Ryu Narimatsu, Kosuke Sasaki, Remi Takenouchi, Yusuke Sato’o, Yoshifumi Aiba, Kotaro Kiga, Teppei Sasahara, Yusuke Taki, Feng-Yu Li, Yuancheng Zhang, Aa Haeruman Azam, Tomofumi Kawaguchi, Longzhu Cui
    Scientific Reports 10 (1) 16907 - 16907 2020/10 [Refereed][Not invited]
     
    Abstract Staphylococcus aureus strains that are susceptible to the β-lactam antibiotic oxacillin despite carrying mecA (OS-MRSA) cause serious clinical problems globally because of their ability to easily acquire β-lactam resistance. Understanding the genetic mechanism(s) of acquisition of the resistance is therefore crucial for infection control management. For this purpose, a whole-genome sequencing-based analysis was performed using 43 clinical OS-MRSA strains and 100 mutants with reduced susceptibility to oxacillin (MICs 1.0–256 µg/mL) generated from 26 representative OS-MRSA strains. Genome comparison between the mutants and their respective parent strains identified a total of 141 mutations in 46 genes and 8 intergenic regions. Among them, the mutations are frequently found in genes related to RNA polymerase (rpoBC), purine biosynthesis (guaA, prs, hprT), (p)ppGpp synthesis (relSau), glycolysis (pykA, fbaA, fruB), protein quality control (clpXP, ftsH), and tRNA synthase (lysS, gltX), whereas no mutations existed in mec and bla operons. Whole-genome transcriptional profile of the resistant mutants demonstrated that expression of genes associated with purine biosynthesis, protein quality control, and tRNA synthesis were significantly inhibited similar to the massive transcription downregulation seen in S. aureus during the stringent response, while the levels of mecA expression and PBP2a production were varied. We conclude that a combination effect of mecA upregulation and stringent-like response may play an important role in acquisition of β-lactam resistance in OS-MRSA.
  • Kanate Thitiananpakorn, Yoshifumi Aiba, Xin-Ee Tan, Shinya Watanabe, Kotaro Kiga, Yusuke Sato’o, Tanit Boonsiri, Feng-Yu Li, Teppei Sasahara, Yusuke Taki, Aa Haeruman Azam, Yuancheng Zhang, Longzhu Cui
    Scientific Reports 10 (1) 16107 - 16107 2020/10 [Refereed][Not invited]
     
    Abstract We first reported a phenomenon of cross-resistance to vancomycin (VCM) and daptomycin (DAP) in methicillin-resistant Staphylococcus aureus (MRSA) in 2006, but mechanisms underlying the cross-resistance remain incompletely understood. Here, we present a follow-up study aimed to investigate genetic determinants associated with the cross-resistance. Using 12 sets of paired DAP susceptible (DAPS) and DAP non-susceptible (DAPR) MRSA isolates from 12 patients who had DAP therapy, we (i) assessed susceptibility to DAP and VCM, (ii) compared whole-genome sequences, (iii) identified mutations associated with cross-resistance to DAP and VCM, and (iv) investigated the impact of altered gene expression and metabolic pathway relevant to the cross-resistance. We found that all 12 DAPR strains exhibiting cross-resistance to DAP and VCM carried mutations in mprF, while one DAPR strain with reduced susceptibility to only DAP carried a lacF mutation. On the other hand, among the 32 vancomycin-intermediate S. aureus (VISA) strains isolated from patients treated with VCM, five out of the 18 strains showing cross-resistance to DAP and VCM carried a mprF mutation, while 14 strains resistant to only VCM had no mprF mutation. Moreover, substitution of mprF in a DAPS strain with mutated mprF resulted in cross-resistance and vice versa. The elevated lysyl-phosphatidylglycerol (L-PG) production, increased positive bacterial surface charges and activated cell wall (CW) synthetic pathways were commonly found in both clinical isolates and laboratory-developed mutants that carry mprF mutations. We conclude that mprF mutation is responsible for the cross-resistance of MRSA to DAP and VCM, and treatment with DAP is more likely to select for mprF-mediated cross-resistance than is with VCM.
  • Kotaro Kiga, Xin-Ee Tan, Rodrigo Ibarra-Chávez, Shinya Watanabe, Yoshifumi Aiba, Yusuke Sato'o, Feng-Yu Li, Teppei Sasahara, Bintao Cui, Moriyuki Kawauchi, Tanit Boonsiri, Kanate Thitiananpakorn, Yusuke Taki, Aa Haeruman Azam, Masato Suzuki, José R Penadés, Longzhu Cui
    Nature communications 11 (1) 2934 - 2934 2020/06 [Refereed][Not invited]
     
    The emergence of antimicrobial-resistant bacteria is an increasingly serious threat to global health, necessitating the development of innovative antimicrobials. Here we report the development of a series of CRISPR-Cas13a-based antibacterial nucleocapsids, termed CapsidCas13a(s), capable of sequence-specific killing of carbapenem-resistant Escherichia coli and methicillin-resistant Staphylococcus aureus by recognizing corresponding antimicrobial resistance genes. CapsidCas13a constructs are generated by packaging programmed CRISPR-Cas13a into a bacteriophage capsid to target antimicrobial resistance genes. Contrary to Cas9-based antimicrobials that lack bacterial killing capacity when the target genes are located on a plasmid, the CapsidCas13a(s) exhibit strong bacterial killing activities upon recognizing target genes regardless of their location. Moreover, we also demonstrate that the CapsidCas13a(s) can be applied to detect bacterial genes through gene-specific depletion of bacteria without employing nucleic acid manipulation and optical visualization devices. Our data underscore the potential of CapsidCas13a(s) as both therapeutic agents against antimicrobial-resistant bacteria and nonchemical agents for detection of bacterial genes.
  • Yoshifumi Aiba, Shinya Watanabe, Rieko Tsukahara, Naoka Umemoto, Kanate Thitiananpakorn, Tanit Boonsiri, Feng-Yu Li, Kotaro Kiga, Yusuke Sato'o, Xin-Ee Tan, Yusuke Taki, Aa Haeruman Azam, Yuancheng Zhang, Teppei Sasahara, Toshio Demitsu, Longzhu Cui
    Microbiology resource announcements 9 (23) 2020/06 [Refereed][Not invited]
     
    The association of Panton-Valentine leukocidin (PVL) toxin with necrotizing soft tissue infection (NSTI) caused by Staphylococcus aureus remains controversial. Here, we report the complete genome sequence of the PVL-negative S. aureus strain JMUB1273, isolated from a patient with pervasive NSTI.
  • Janyerkye Tulyeu, Hideki Kumagai, Eriko Jimbo, Shinya Watanabe, Koji Yokoyama, Longzhu Cui, Hitoshi Osaka, Makiko Mieno, Takanori Yamagata
    Microorganisms 7 (10) 463  2019/10 [Refereed][Not invited]
  • Dai Akine, Teppei Sasahara, Shinya Watanabe, Yohei Ishishita, Takashi Yamaguchi, Longzhu Cui, Yuji Morisawa
    IDCases 18 e00622  2019/08 [Refereed][Not invited]
     
    Klebsiella variicola, a member of K. pneumoniae phylogroup, can cause severe infectious diseases. We report a case of K. variicola meningitis after neurosurgery. The bacterium was isolated from blood and cerebrospinal fluid, and bacterial species identification was carried out by using both matrix-assisted laser-desorption/ionization time-of-flight mass spectroscopy (MALDI-TOF MS) and whole genome sequencing. Initially, the organism was misidentified as K. pneumoniae by VITEK®2; automated system in the clinical laboratory examination. The patient recovered with the combination of surgical drainage and antimicrobial treatment. To our knowledge, this is the first case report of post-surgical meningitis caused by K. variicola. As experienced in this case, the automated bacterial identification system popularly being used in the clinical laboratory might not be effective enough for bacterial species identification. The use of MALDI-TOF MS for microbial identification may be helpful to physicians for appropriate management of K. pneumoniae phylogroup infection.
  • Shinya Watanabe, Bintao Cui, Kotaro Kiga, Yoshifumi Aiba, Xin-Ee Tan, Yusuke Sato'o, Moriyuki Kawauchi, Tanit Boonsiri, Kanate Thitiananpakorn, Yusuke Taki, Fen-Yu Li, Aa Haeruman Azam, Yumi Nakada, Teppei Sasahara, Longzhu Cui
    Frontiers in microbiology 10 2838 - 2838 2019 [Refereed][Not invited]
     
    Clustered regularly interspaced short palindromic repeats (CRISPR)-Cas13a, previously known as CRISPR-C2c2, is the most recently identified RNA-guided RNA-targeting CRISPR-Cas system that has the unique characteristics of both targeted and collateral single-stranded RNA (ssRNA) cleavage activities. This system was first identified in Leptotrichia shahii. Here, the complete whole genome sequences of 11 Leptotrichia strains were determined and compared with 18 publicly available Leptotrichia genomes in regard to the composition, occurrence and diversity of the CRISPR-Cas13a, and other CRISPR-Cas systems. Various types of CRISPR-Cas systems were found to be unevenly distributed among the Leptotrichia genomes, including types I-B (10/29, 34.4%), II-C (1/29, 2.6%), III-A (6/29, 15.4%), III-D (6/29, 15.4%), III-like (3/29, 7.7%), and VI-A (11/29, 37.9%), while 8 strains (20.5%) had no CRISPR-Cas system at all. The Cas13a effectors were found to be highly divergent with amino acid sequence similarities ranging from 61% to 90% to that of L. shahii, but their collateral ssRNA cleavage activities leading to impediment of bacterial growth were conserved. CRISPR-Cas spacers represent a sequential achievement of former intruder encounters, and the retained spacers reflect the evolutionary phylogeny or relatedness of strains. Analysis of spacer contents and numbers among Leptotrichia species showed considerable diversity with only 4.4% of spacers (40/889) were shared by two strains. The organization and distribution of CRISPR-Cas systems (type I-VI) encoded by all registered Leptotrichia species revealed that effector or spacer sequences of the CRISPR-Cas systems were very divergent, and the prevalence of types I, III, and VI was almost equal. There was only one strain carrying type II, while none carried type IV or V. These results provide new insights into the characteristics and divergences of CRISPR-Cas systems among Leptotrichia species.
  • Izumo Kanesaka, Shingo Fujisaki, Yoshifumi Aiba, Shinya Watanabe, Takashi Mikawa, Akiko Kanayama Katsuse, Hiroshi Takahashi, Longzhu Cui, Intetsu Kobayashi
    Journal of Infection and Chemotherapy 25 (1) 1 - 5 2019/01 [Refereed][Not invited]
  • Bintao Cui, Shinya Watanabe, Yusuke Sato'o, Fumiya Nihashi, Yoshifumi Aiba, Kotaro Kiga, Teppei Sasahara, Xin-Ee Tan, Moriyuki Kawauchi, Tanit Boonsiri, Kanate Thitiananpakorn, Yusuke Taki, Feng-Yu Li, Shiro Imokawa, Longzhu Cui
    Microbiology resource announcements 8 (4) e01652-18  2019/01 [Refereed][Not invited]
     
    Severe community-acquired pneumonia (CAP) caused by methicillin-resistant Staphylococcus aureus (MRSA) is relatively rare and is usually associated with rapid progression to death. Here, we report the complete genome sequence of the MRSA strain JMUB3031, which was isolated from a patient with fatal CAP.
  • Shinya Watanabe, Yoshifumi Aiba, Xin-Ee Tan, Feng-Yu Li, Tanit Boonsiri, Kanate Thitiananpakorn, Bintao Cui, Yusuke Sato'o, Kotaro Kiga, Teppei Sasahara, Longzhu Cui
    BMC genomics 19 (1) 810 - 810 2018/11 [Refereed][Not invited]
     
    BACKGROUND: Staphylococcus caprae is an animal-associated bacterium regarded as part of goats' microflora. Recently, S. caprae has been reported to cause human nosocomial infections such as bacteremia and bone and joint infections. However, the mechanisms responsible for the development of nosocomial infections remain largely unknown. Moreover, the complete genome sequence of S. caprae has not been determined. RESULTS: We determined the complete genome sequences of three methicillin-resistant S. caprae strains isolated from humans and compared these sequences with the genomes of S. epidermidis and S. capitis, both of which are closely related to S. caprae and are inhabitants of human skin capable of causing opportunistic infections. The genomes showed that S. caprae JMUB145, JMUB590, and JMUB898 strains contained circular chromosomes of 2,618,380, 2,629,173, and 2,598,513 bp, respectively. JMUB145 carried type V SCCmec, while JMUB590 and JMUB898 had type IVa SCCmec. A genome-wide phylogenetic SNP tree constructed using 83 complete genome sequences of 24 Staphylococcus species and 2 S. caprae draft genome sequences confirmed that S. caprae is most closely related to S. epidermidis and S. capitis. Comparative complete genome analysis of eight S. epidermidis, three S. capitis and three S. caprae strains revealed that they shared similar virulence factors represented by biofilm formation genes. These factors include wall teichoic acid synthesis genes, poly-gamma-DL-glutamic acid capsule synthesis genes, and other genes encoding nonproteinaceous adhesins. The 17 proteinases/adhesins and extracellular proteins known to be associated with biofilm formation in S. epidermidis were also conserved in these three species, and their biofilm formation could be detected in vitro. Moreover, two virulence-associated gene clusters, the type VII secretion system and capsular polysaccharide biosynthesis gene clusters, identified in S. aureus were present in S. caprae but not in S. epidermidis and S. capitis genomes. CONCLUSION: The complete genome sequences of three methicillin-resistant S. caprae isolates from humans were determined for the first time. Comparative genome analysis revealed that S. caprae is closely related to S. epidermidis and S. capitis at the species level, especially in the ability to form biofilms, which may lead to increased virulence during the development of S. caprae infections.
  • Yusuke Sato'o, Yoshifumi Aiba, Kotaro Kiga, Shinya Watanabe, Teppei Sasahara, Yasuhiko Hayakawa, Longzhu Cui
    Journal of microbiological methods 146 25 - 32 0167-7012 2018/03 [Refereed][Not invited]
     
    Electroporation is a common technique necessary for genomic manipulation of Staphylococci. However, because this technique has too low efficiency to be applied to some Staphylococcal species and strains, especially to coagulase-negative Staphylococcus (CNS) isolates, basic researches on these clinically important Staphylococci are limited. Here we report on the optimization of electroporation parameters and conditions as well as on the generation of a universal protocol that can be efficiently applicable to both CNS and Coagulase-positive Staphylococci (CPS). This protocol could generate transformants of clinical Staphylococcus epidermidis isolate, with an efficiency of up to 1400 CFU/μg of plasmid DNA. Transformants of 12 other clinically important Staphylococcal species, including CNS and CPS, were also generated with this protocol. To our knowledge, this is the first report on successful electroporation in nine these Staphylococcal species.
  • Kohei Ogura, Shinya Watanabe, Teruo Kirikae, Tohru Miyoshi-Akiyama
    Journal of Genomics 5 71 - 74 2017/07 [Refereed][Not invited]
     
    Epidemiologic typing of Streptococcus pyogenes (GAS) is frequently based on the genotype of the emm gene, which encodes M/Emm protein. In this study, the complete genome sequence of GAS emm3 strain M3-b, isolated from a patient with streptococcal toxic shock syndrome (STSS), was determined. This strain exhibited 99% identity with other complete genome sequences of emm3 strains MGAS315, SSI-1, and STAB902. The complete genomes of five additional strains isolated from Japanese patients with and without STSS were also sequences. Maximum-likelihood phylogenetic analysis showed that strains M3-b, M3-e, and SSI-1, all which were isolated from STSS patients, were relatively close.
  • Takemoto N, Ogura K, Watanabe S, Miyoshi-Akiyama T
    Japanese Journal of Chemotherapy 65 (5) 745 - 750 2017 [Refereed][Not invited]
  • Shinya Watanabe, Kazunori Matsumura, Hiroki Iwai, Keiji Funatogawa, Yuji Haishima, Chie Fukui, Kayo Okumura, Masako Kato-Miyazawa, Masahito Hashimoto, Kanae Teramoto, Fumiko Kirikae, Tohru Miyoshi-Akiyama, Teruo Kirikaea
    Infection and immunology 84 (8) 2264 - 2273 0019-9567 2016/08 [Refereed][Not invited]
     
    Mycobacterium tuberculosis contains a single rRNA operon that encodes targets for antituberculosis agents, including kanamycin. To date, only four mutations in the kanamycin binding sites of 16S rRNA have been reported in kanamycin-resistant clinical isolates. We hypothesized that another mutation(s) in the region may dramatically decrease M. tuberculosis viability and virulence. Here, we describe an rRNA mutation, U1406A, which was generated in vitro and confers resistance to kanamycin while highly attenuating M. tuberculosis virulence. The mutant showed decreased expression of 20% (n = 361) of mycobacterial proteins, including central metabolic enzymes, mycolic acid biosynthesis enzymes, and virulence factors such as antigen 85 complexes and ESAT-6. The mutation also induced three proteins, including KsgA (Rv1010; 16S rRNA adenine dimethyltransferase), which closely bind to the U1406A mutation site on the ribosome; these proteins were associated with ribosome maturation and translation initiation processes. The mutant showed an increase in 17S rRNA (precursor 16S rRNA) and a decrease in the ratio of 30S subunits to the 70S ribosomes, suggesting that the U1406A mutation in 16S rRNA attenuated M. tuberculosis virulence by affecting these processes.
  • Shinya Watanabe, Teppei Sasahara, Naoshi Arai, Kazumasa Sasaki, Yoshifumi Aiba, Yusuke Sato'o, Longzhu Cui
    Genome Announcements 4 (5) e01133-16  2169-8287 2016 [Refereed][Not invited]
     
    Acute phlegmonous gastritis is an uncommon endogenous bacterial gastritis presenting with a high mortality rate. Here, we report the complete genome sequence of an emm89 Streptococcus pyogenes strain, JMUB1235, which is the causative agent of acute phlegmonous gastritis.
  • Shinya Watanabe, Norihiko Takemoto, Kohei Ogura, Tohru Miyoshi-Akiyama
    Microbiology and immunology 60 (1) 1 - 9 0385-5600 2016/01 [Not refereed][Invited]
     
    Streptococcus pyogenes, a group A Streptococcus (GAS), has been recognized as the causative pathogen in patients with severe invasive streptococcal infection with or without necrotizing fasciitis. In recent epidemiological studies, Streptococcus dysgalactiae subsp. equisimilis (SDSE) has been isolated from severe invasive streptococcal infection. Complete genome sequence showed that SDSE is the closest bacterial species to GAS, with approximately 70% of genome coverage. SDSE, however, lacks several key virulence factors present in GAS, such as SPE-B, the hyaluronan synthesis operon and active superantigen against human immune cells. A key event in the ability of GAS to cause severe invasive streptococcal infection was shown to be the acquisition of novel genetic traits such as phages. Strikingly, however, during severe invasive infection, GAS destroys its own covRS two-component system, which negatively regulates many virulence factor genes, resulting in a hyper-virulent phenotype. In contrast, this phenomenon has not been observed in SDSE. The present review describes the epidemiology of severe invasive streptococcal infection and the detailed pathogenic mechanisms of GAS and SDSE, emphasizing findings from their genome sequences and analyses of gene expression.
  • Hiroki Ando, Tohru Miyoshi-Akiyama, Shinya Watanabe, Teruo Kirikae
    Molecular microbiology 91 (3) 538 - 547 0950-382X 2014/02 [Refereed][Not invited]
     
    Drug resistance in Mycobacterium tuberculosis (Mtb) is caused by mutations in restricted regions of the genome. Mutations in katG, the promoter region of the mabA-inhA operon, and inhA are those most frequently responsible for isoniazid (INH) resistance. Several INH-resistant (INHr) Mtb clinical isolates without mutations in these regions have been described, however, indicating that there are as yet undetermined mechanisms of INH resistance. We identified the mabA(g609a) silent mutation in a significant number of INHr Mtb clinical isolates without known INH resistance mutations. A laboratory strain, H37Rv, constructed with mabA(g609a), was resistant to INH. We show here that the mabA(g609a) mutation resulted in the upregulation of inhA, a gene encoding a target for INH, converting the region adjacent to the mutation into an alternative promoter for inhA. The mabA(g609a) silent mutation results in a novel mechanism of INH resistance, filling in a missing piece of INH resistance in Mtb.
  • Shinya Watanabe, Yumi Shimomura, Kimiko Ubukata, Teruo Kirikae, Tohru Miyoshi-Akiyama
    Journal of Infectious Diseases 208 (9) 1482 - 1493 0022-1899 2013/11 [Refereed][Not invited]
     
    Background. Streptococcus dysgalactiae subsp. equisimilis (SDSE) has Lancefield group G or C antigens. Recent epidemiological studies reveal that invasive SDSE infections have been increasing in Asia, Europe, and the United States. The mechanisms and key virulence factors by which SDSE causes invasive diseases are poorly understood.Methods. We analyzed the SDSE transcriptome in vivo during intraperitoneal infection in mice. We also compared the abundance of streptolysin S (SLS) and streptolysin O (SLO) production between clinically dominant stG6792 strains and other clinical isolates.Results. Microarray data suggest that SDSE degraded host tissue polysaccharides by secreting poly/oligosaccharide lyases and simultaneously used the Entner-Doudoroff pathway to metabolize acquired carbohydrates. A global negative virulence gene regulator CsrRS of SDSE modulated the expression of genes encoding SLS and enzymes that metabolize carbohydrates. Moreover, a csrS-deficient mutant induced severe systemic hemolysis in mice. The most frequently isolated stG6792 strains secreted abundant SLS and SLO rather than other SDSE emm types, indicating the potential relationship between production of SLS and SLO and poor outcomes.Conclusions. Our findings suggest that the concomitant regulation of virulence factors that destroy host tissues and metabolic enzymes might play an important role in invasive diseases induced by SDSE. © The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved.
  • Shinya Watanabe, Teruo Kirikae, Tohru Miyoshi-Akiyama
    Genome biology and evolution 5 (9) 1644 - 1651 1759-6653 2013 [Refereed][Not invited]
     
    Streptococcus dysgalactiae subsp. equisimilis (SDSE) is an emerging human pathogen that causes life-threatening invasive infections such as streptococcal toxic shock syndrome. Recent epidemiological studies reveal that invasive SDSE infections have been increasing in Asia, Europe, and the United States. Almost all SDSE carry Lancefield group G or C antigen. We have determined the complete genome sequence of a human group C SDSE 167 strain. A comparison of its sequence with that of four SDSE strains, three in Lancefield group G and one in Lancefield group A, showed approximately 90% coverage. Most regions showing little or no homology were located in the prophages. There was no evidence of massive rearrangement in the genome of SDSE 167. Bayesian phylogeny using entire genome sequences showed that the most recent common ancestor of the five SDSE strains appeared 446 years ago. Interestingly, we found that SDSE 167 harbors sugar metabolizing enzymes in a unique region and streptodornase in the phage region, which presumably contribute to the degradation of host tissues and the prompted covRS mutation, respectively. A comparison of these five SDSE strains, which differ in Lancefield group antigens, revealed a gene cluster presumably responsible for the synthesis of the antigenic determinant. These results may provide the basis for molecular epidemiological research of SDSE.
  • Tohru Miyoshi-Akiyama, Shinya Watanabe, Teruo Kirikae
    Journal of bacteriology 194 (19) 5466 - 5466 0021-9193 2012/10 [Refereed][Not invited]
     
    Here, we report the completely annotated genome sequence of Streptococcus pyogenes M1 476 isolated from a patient with streptococcal toxic shock syndrome (STSS) during pregnancy. The genome sequence will provide new insights into the mechanisms underlying STSS.
  • Ken Hisata, Teruyo Ito, Nobuaki Matsunaga, Mitsutaka Komatsu, Jingxun Jin, Shanshuang Li, Shinya Watanabe, Toshiaki Shimizu, Keiichi Hiramatsu
    Journal of infection and chemotherapy 17 (5) 609 - 621 1341-321X 2011/10 [Refereed][Not invited]
     
    The proportion of MRSA strains that cause skin and soft infections has recently increased. In 3 months we have characterized 17 MRSA strains isolated from children with impetigo at a Japanese hospital. Seventeen MRSA strains belonged to 7 clones defined by clonal complex (CC) in MLST genotype and type of SCCmec, which were rarely identified among healthcare-associated MRSA: CC 91-SCCmecIIb (4 strains); CC91-SCCmecIIn (2 strains); CC91-SCCmecIVa (2 strains); CC91-SCCmecV (4 strains); CC88-SCCmecIVg (3 strains); CC1-SCCmecIVc (1 strain); and CC5-SCCmecIVn (1 strain). Although one strain belonged to CC5, which has been commonly identified in healthcare-associated MRSA, it did not carry type II SCCmec, but carried type IV SCCmec. Fourteen of the 17 strains carried exfoliative toxin a or b gene, and none carried Panton-Valentine leukocidine gene. Furthermore, we determined the entire nucleotide sequences of two type V SCCmec elements carried by strains JCSC5952, a CC91 strain, and TSGH17, a Taiwanese CC59 strain. The structure of SCCmecJCSC5952 was more than 99% homologous in nucleotide identity with those of Taiwanese PVL-positive ST59 MRSA strains TSGH17 and PM1, which were designated as type V (5C2&5). Identification of multiple MRSA clones distinct from those disseminating at the hospital suggests that MRSA strains might be emerging in the community from MSSA strains by acquiring SCCmec elements on various occasions. Carriage of the similar type V(5C2&5) SCCmec element by strains of distinct genetic backgrounds, CC91 and CC59, suggested horizontal transfer of the SCCmec element.
  • Shinya Watanabe, Michael Zimmermann, Michael B. Goodwin, Uwe Sauer, Clifton E. Barry, Helena I. Boshoff
    Plos pathogens 7 (10) e1002287  1553-7366 2011/10 [Refereed][Not invited]
     
    Oxygen depletion of Mycobacterium tuberculosis engages the DosR regulon that coordinates an overall down-regulation of metabolism while up-regulating specific genes involved in respiration and central metabolism. We have developed a chemostat model of M. tuberculosis where growth rate was a function of dissolved oxygen concentration to analyze metabolic adaptation to hypoxia. A drop in dissolved oxygen concentration from 50 mmHg to 0.42 mmHg led to a 2.3 fold decrease in intracellular ATP levels with an almost 70-fold increase in the ratio of NADH/NAD(+). This suggests that re-oxidation of this co-factor becomes limiting in the absence of a terminal electron acceptor. Upon oxygen limitation genes involved in the reverse TCA cycle were upregulated and this upregulation was associated with a significant accumulation of succinate in the extracellular milieu. We confirmed that this succinate was produced by a reversal of the TCA cycle towards the non-oxidative direction with net CO(2) incorporation by analysis of the isotopomers of secreted succinate after feeding stable isotope ((13)C) labeled precursors. This showed that the resulting succinate retained both carbons lost during oxidative operation of the TCA cycle. Metabolomic analyses of all glycolytic and TCA cycle intermediates from (13)C-glucose fed cells under aerobic and anaerobic conditions showed a clear reversal of isotope labeling patterns accompanying the switch from normoxic to anoxic conditions. M. tuberculosis encodes three potential succinate-producing enzymes including a canonical fumarate reductase which was highly upregulated under hypoxia. Knockout of frd, however, failed to reduce succinate accumulation and gene expression studies revealed a compensatory upregulation of two homologous enzymes. These major realignments of central metabolism are consistent with a model of oxygen-induced stasis in which an energized membrane is maintained by coupling the reductive branch of the TCA cycle to succinate secretion. This fermentative process may offer unique targets for the treatment of latent tuberculosis.
  • Shinya Watanabe, Teruyo Ito, Takashi Sasaki, Shanshuang Li, Ikuo Uchiyama, Kozue Kishii, Ken Kikuchi, Robert Leo Skov, Keiichi Hiramatsu
    PLOS ONE 4 (5) e5714  1932-6203 2009/05 [Refereed][Not invited]
     
    Background: The production of staphylocoagulase (SC) causing the plasma coagulation is one of the important characteristics of Staphylococcus aureus. Although SCs have been classified into 10 serotypes based on the differences in the antigenicity, genetic bases for their diversities and relatedness to chromosome types are poorly understood. Methodology/Principal Findings: We compared the nucleotide sequences of 105 SC genes (coa), 59 of which were determined in this study. D1 regions, which contain prothrombin-activating and -binding domains and are presumed to be the binding site of each type-specific antiserum, were classified into twelve clusters having more than 90% nucleotide identities, resulting to create two novel SC types, XI and XII, in addition to extant 10 types. Nine of the twelve SC types were further subdivided into subtypes based on the differences of the D2 or the central regions. The phylogenetical relations of the D1 regions did not correlate exactly with either one of agr types and multilocus sequence types (STs). In addition, genetic analysis showed that recombination events have occurred in and around coa. So far tested, STs of 126 S. aureus strains correspond to the combination of SC type and agr type except for the cases of CC1 and CC8, which contained two and three different SC types, respectively. Conclusion: The data suggested that the evolution of coa was not monophyletic in the species. Chromosomal recombination had occurred at coa and agr loci, resulting in the carriage of the combinations of allotypically different important virulence determinants in staphylococcal chromosome.
  • Carolina Berglund, Teruyo Ito, Xiao Xue Ma, Megumi Ikeda, Shinya Watanabe, Bo Soderquist, Keiichi Hiramatsu
    JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY 63 (1) 32 - 41 0305-7453 2009/01 [Refereed][Not invited]
     
    Recent studies have shown a predominance of type IV SCCmec among the methicillin-resistant Staphylococcus aureus (MRSA) isolated in the low endemic areas of Orebro County and the western region of Sweden. However, many of these isolates were not possible to classify as existing subtypes IVa, IVb, IVc or IVd. We analysed 16 such MRSA isolates by multilocus sequence typing, spa typing, staphylocoagulase (SC) typing and detection of type IVg and IVh SCCmec. MRSA that remained as unknown type IV SCCmec were investigated by long-range PCR covering the J1 region; however, only two isolates were possible to amplify by PCR. The nucleotide sequences of the entire SCCmec of these two MRSA were determined. In addition, isolates that had unknown SC types were investigated by nucleotide sequencing of the coa genes. Five of 16 isolates were classified as type IVg SCCmec, and four isolates had type IVh SCCmec. Two subtypes of type IV SCCmec shared J1 regions previously identified in other types of SCCmec, types I.2 and II.2. The novel elements were designated as type IVi and IVj SCCmec. In addition, the genetic backgrounds of these Swedish MRSA were diverse and constituted at least nine sequence types and eight SC types, including four new types of SC. Type IV SCCmec is occurring in heterogeneous clones of MRSA in Sweden, and the majority of the type IV SCCmec were identified in community-acquired MRSA. We describe two novel subtypes of type IV SCCmec with common J1 regions shared by other types of SCCmec, which indicate that J1 regions occurred as primordial SCC.
  • Fumihiko Sakai, Atsuhiro Takemoto, Shinya Watanabe, Kenji Aoyama, Tatsuro Ohkubo, Shuichi Yanahira, Hideo Igarashi, Shunji Kozaki, Keiichi Hiramatsu, Teruyo Ito
    Journal of microbiological methods 75 (2) 312 - 317 0167-7012 2008/10 [Refereed][Not invited]
     
    Staphylocoagulases (SCs) have been classified by the differences in antigenicity using a serological method. We have developed a system to classify them based on the nucleotide differences in SC genes (coa). The system was of three multiplex PCRs (M-PCRs): M-PCR:A, identifying types III, IV, VII, and VIII; M-PCR:B, identifying types I, II, V, and VI; M-PCR:C, identifying three subtypes of type VI. In this study, we found that coo genes of the serotype VI were not identical, but classified into three subtypes based on the nucleotide differences, especially in D2 and the central region: Via, the coa gene carried by stp12 from human; and VIb and VIc, the coa genes carried by strains IFH556 and IFH514 isolated from bovine raw milk. The primer pair used in M-PCR:B was designed to identify all three subtypes of type VI coa. The results showed that coa types of 154 out of 155 Staphylococcus aureus strains from various origins assigned by M-PCR:A and B were identical to those obtained by serological methods, leaving a serotype IV strain unclassifiable. All 73 type VI strains were classified into one of three subtypes by M-PCR:C. Furthermore, we found that type Via and VIb strains carried characteristic pyrogenic toxin superantigen genes, while no toxin genes were identified in type VIc strains, suggesting the correlation between the subtype of type VI coa gene and the carriage of genomic islands. Our results showed that these M-PCRs are convenient methods for SC typing that might be useful for epidemiological studies. (C) 2008 Elsevier B.V. All rights reserved.
  • Kozue Kishii, Teruyo Ito, Shinya Watanabe, Katsuko Okuzumi, Keiichi Hiramatsu
    Journal of antimicrobial chemotherapy 62 (2) 324 - 328 0305-7453 2008/08 [Refereed][Not invited]
     
    Objectives: In the early 1980s, heterogeneous methicillin-resistant Staphylococcus aureus (hetero-MRSA) strains were predominant in the University of Tokyo Hospital. But, in the 1990s, they were completely substituted by homogeneously highly methicillin-resistant S. aureus (homo-MRSA) strains. Since 2000, however, we started observing an increase in MRSA strains with low cefazolin MICs (MRCLSA). This study was performed to understand the phenomenon by characterization of the 'cefazolin-susceptible' MRSA strains. Methods: A total of 39 MRCLSA strains were collected between July 2000 and June 2002 and compared with 10 homo-MRSA strains isolated during the same period for their antibiograms and genotypes. The strains were also compared with the hetero-MRSA strains isolated in the same hospital in the early 1980s. Results: In contrast to the homogeneous genotype [multilocus sequence type 5 and SCCmec type II.1 (IIa)] and multiresistant nature of the homo-MRSA strains, the MRCLSA strains were composed of various genotypes as revealed by multilocus sequence typing and SCCmec typing and had resistance only to a limited number of antibiotics. Most of the MRCLSA strains were also genetically differentiated from the hetero-MRSA strains of the 1980s. However, population analysis revealed that all of the MRCLSA strains were classified as hetero-MRSA strains. Conclusions: A new group of hetero-MRSA strains genetically distinct from those dominant in the same hospital in the early 1980s might have emerged in the community and started invading the university hospital. This phenomenon may be caused by the change in the pattern of antibiotic use.
  • Cristina Reinert, John Anthony McCulloch, Shinya Watanabe, Teruyo Ito, Keiichi Hiramatsu, Elsa Masae Mamizuka
    Brazilian journal of infectious diseases 12 (3) 213 - 216 1413-8670 2008/06 [Refereed][Not invited]
     
    Methicillin-resistant Staphylococcus aureus (MRSA) commonly causes infection in hospitalized patients. Since its appearance in the 1960s, the SCCmec has evolved throughout the years into 5 different types (I-V), each bearing a different set of genes. Infection with MRSA SCCmec types I, II or III is almost exclusively restricted to hospitalised patients. However, recently, community acquired MRSA (CA-MRSA) infections have been reported with increasing frequency, usually caused by a type IV SCCmec MRSA in nosocomial settings. We studied the prevalence of SCCmec types in 50 nosocomial strains collected from 1995 to 1999. The SCCmec complex type and presence of Panton-Valentine leukocidin (PVL) were determined by PCR. Strains had been previously typed by PFGE and were now typed by MLST. We found that 3 of the isolates studied bore a type IVc SCCmec all having different PFGE and MLST profiles (ST3, ST5 and ST88). All strains bearing a type III SCCmec belonged to MLST ST239 (Brazilian/Iberian clone). Only the strain which presented the ST5 profile bore the pvl gene. The type IVc SCCmec strains presented relatively lower levels of resistance to oxacillin in comparison to the type III SCCmec strains. The pattern of dissemination of the type IV SCCmec remains to be elucidated. The finding of strains carrying a type IV SCCmec in the present study among strains isolated at least 7 years ago indicates that clones bearing a type IV SCCmec have been present in Brazil for quite some time, and must have gone by undetected.
  • Shinya Watanabe, Teruyo Ito, Keiichi Hiramatsu
    Journal of antimicrobial chemotherapy 60 (6) 1384 - 1387 0305-7453 2007/12 [Refereed][Not invited]
     
    Objectives: The aim of the study was to test in vitro activities of the novel des-F(6)-quinolone DX-619 against methicillin-resistant staphylococci (MRS) isolated in hospitals and communities and to compare its activity with other quinolones, sitafloxacin and levofloxacin, and antibiotics used for the treatment of methicillin-resistant Staphylococcus aureus infection, including vancomycin, teicoplanin, arbekacin, linezolid and quinupristin/dalfopristin. Methods: MICs were determined by the agar dilution method using healthcare-associated MRS (S. aureus including strains with reduced susceptibility to vancomycin, 103; coagulase-negative staphylococci, 87) and community-associated MRS (S. aureus including non-multiresistant oxacillin-resistant strains, 37; coagulase-negative staphylococci, 92). The quinolone resistance-determining regions of gyrA, gyrB, grlA and grlB genes from six strains with reduced susceptibility to DX-619 were sequenced. Results: DX-619 showed the lowest MIC90 values for all categories of strains tested, irrespective of the degree of glycopeptide resistance. The six strains with MIC values of >128 mg/L of levofloxacin commonly carried two mutations in gyrA and two mutations in grlA. DX-619 showed potent activity against strains with MIC values of 2 mg/L. Conclusions: DX-619 was potent against all MRS tested, suggesting that it would be a promising candidate for the treatment of methicillin-resistant S. aureus infection if sufficient in vivo concentrations were safely attained.
  • Shinya Watanabe, Teruyo Ito, Yuh Morimoto, Fumihiko Takeuchi, Keiichi Hiramatsu
    Journal of bacteriology 189 (7) 2921 - 2925 0021-9193 2007/04 [Refereed][Not invited]
     
    Large-scale chromosomal inversions (455 to 535 kbp) or deletions (266 to 320 kbp) were found to accompany spontaneous loss of beta-lactam resistance during drug-free passage of the multiresistant Staphylococcus haemolyticus clinical strain JCSC1435. Identification and sequencing of the rearranged chromosomal loci revealed that ISSha1 of S. haemolyticus is responsible for the chromosome rearrangements.
  • Yoko Kondo, Teruyo Ito, Xiao Xue Ma, Shinya Watanabe, Barry N. Kreiswirth, Jerome Etienne, Keiichi Hiramatsu
    Antimicrobial agent and chemotherapy 51 (1) 264 - 274 0066-4804 2007/01 [Refereed][Not invited]
     
    Staphylococcal cassette chromosome mec (SCCmec) typing, in combination with genotyping of the Staphylococcus aureus chromosome, has become essential for defining methicillin-resistant S. aureus (MRSA) clones in epidemiological studies. We have developed a convenient system for SCCmec type assignment. The system consists of six multiplex PCRs (M-PCRs) for identifying the ccr gene complex (ccr), the mec gene complex (mec), and specific structures in the junkyard (J) regions: M-PCR with primer set I (M-PCR 1) identified five types of ccr genes; M-PCR 2 identified class A to class C mec; M-PCRs 3 and 4 identified specific open reading frames in the J1 regions of type I and IV and of type II, III, and V SCCmec elements, respectively; M-PCR 5 identified the transposons Tn554 and psi Tn554 integrated into the J2 regions of type II and III SCCmec elements; and M-PCR 6 identified plasmids pT181 and pUB110 integrated into J3 regions. The system was validated with 99 MRSA strains carrying SCCmec elements of different types. The SCCmec types of 93 out of the 99 MRSA strains could be assigned. The SCCmec type assignments were identical to those made with a PCR system that uses numerous primer pairs to identify genes or gene alleles. Our system of six M-PCRs is thus a convenient and reliable method for typing SCCmec elements.
  • F Takeuchi, S Watanabe, T Baba, H Yuzawa, T Ito, Y Morimoto, M Kuroda, LZ Cui, M Takahashi, A Ankai, S Baba, S Fukui, JC Lee, K Hiramatsu
    Journal of bacteriology 187 (21) 7292 - 7308 0021-9193 2005/11 [Refereed][Not invited]
     
    Staphylococcus haemolyticus is an opportunistic bacterial pathogen that colonizes human skin and is remarkable for its highly antibiotic-resistant phenotype. We determined the complete genome sequence of S. haemolyticus to better understand its pathogenicity and evolutionary relatedness to the other staphylococcal species. A large proportion of the open reading frames in the genomes of S. haemolyticus, Staphylococcus aureus, and Staphylococcus epidermidis were conserved in their sequence and order on the chromosome. We identified a region of the bacterial chromosome just downstream of the origin of replication that showed little homology among the species but was conserved among strains within a species. This novel region, designated the "oriC environ," likely contributes to the evolution and differentiation of the staphylococcal species, since it was enriched for species-specific nonessential genes that contribute to the biological features of each staphylococcal species. A comparative analysis of the genomes of S. haemolyticus, S. aureus, and S. epidermidis elucidated differences in their biological and genetic characteristics and pathogenic potentials. We identified as many as 82 insertion sequences in the S. haemolyticus chromosome that probably mediated frequent genomic rearrangements, resulting in phenotypic diversification of the strain. Such rearrangements could have brought genomic plasticity to this species and contributed to its acquisition of antibiotic resistance.
  • S Watanabe, T Ito, F Takeuchi, A Endo, E Okuno, K Hiramatsu
    Journal of bacteriology 187 (11) 3698 - 3707 0021-9193 2005/06 [Refereed][Not invited]
     
    Staphylocoagulase detection is the hallmark of a Staphylococcus aureus infection. Ten different serotypes of staphylocoagulases have been reported to date. We determined the nucleotide sequences of seven staphylocoagulase genes (coa) and their surrounding regions to compare structures of all 10 staphylocoagulase serotypes, and we inferred their derivations. We found that all staphylocoagulases are comprised of six regions: signal sequence, D1 region, D2 region, central region, repeat region, and C-terminal sequence. Amino acids at both ends, 33 amino acids in the N terminal (the signal sequences and the seven N-terminal amino acids in the D1 region) and 5 amino acids in the C terminal, were exactly identical among the 10 serotypes. The central regions were conserved with identities between 80.6 and 94.1% and similarities between 82.8 and 94.6%. Repeat regions comprising tandem repeats of 27 amino acids with a 92% identity on average were polymorphic in the number of repeats. On the other hand, DI regions other than the seven N-terminal amino acids and D2 regions were less homologous, with diverged identities from 41.5 to 84.5% and 47.0 to 88.9%, respectively, and similarities from 53.5 to 88.7% and 56.8 to 91.9%, respectively, although the predicted prothrombin-binding sites were conserved among them. In contrast, flanking regions of coa were highly homologous, with nucleotide identities of more than 97.1%. Phylogenetic relations among coa did not correlate with those among the flanking regions or housekeeping genes used for multilocus sequence typing. These data indicate that coa could be transmitted to S. aureus, while the less homologous regions in coa presumed to be responsible for different antigenicities might have evolved independently.
  • K Hiramatsu, S Watanabe, F Takeuchi, T Ito, T Baba
    Vaccine 22 S5 - S8 0264-410X 2004/12 [Refereed][Not invited]
     
    The genome structure of Staphylococcus aureus is analyzed. The genome is composed of two domains. The first domain, descendent from an ancestral bacterial species, contains house-keeping genes that showed highest homology to those of Bacillus species. The second domain contained the genes responsible for virulence and drug-resistance in human infection that seems to have been acquired from other bacterial species via lateral gene transfer. The latter domain constitutes the genetic information that makes S. aureus a notorious hospital pathogen. (C) 2004 Elsevier Ltd. All rights reserved.

MISC

  • 食物アレルギーにおいて腸内細菌叢が腸管上皮タイトジャンクションへ及ぼす影響
    熊谷 秀規, ジャネルケ・トゥレウ, 神保 恵理子, 渡邊 真弥, 幸喜 富, 横山 孝二, 小坂 仁, 山形 崇倫  日本小児栄養消化器肝臓学会雑誌  33-  (2)  134  -134  2019/12  [Not refereed][Not invited]
  • 国内外ファージ研究の状況と推進すべき研究開発戦略に関する提言
    崔 龍洙, 氣駕 恒太朗, 渡邊真弥  JST-CRDS(研究開発の俯瞰報告書)  2019/03  [Not refereed][Not invited]
  • 溶連菌感染症の歴史
    渡邊真弥, 崔龍洙  小児科  59-  (11)  1511  -1518  2018/10  [Refereed][Invited]
  • 次世代シーケンス(NGS)による劇症型レンサ球菌の病原性解析
    竹本訓彦, 小倉康平, 渡邊真弥, 秋山徹  日本化学療法学会雑誌  65-  745  -750  2017  [Not refereed][Not invited]
  • ゲノム解析に基づく劇症型レンサ球菌感染症の分子疫学
    渡邊真弥, 秋山 徹  化学療法の領域  29-  41  -47  2013  [Not refereed][Not invited]
  • 渡邊 真弥, 伊藤 輝代, 森本 ゆふ, 竹内 史比古, 平松 啓一  日本細菌学雑誌  62-  (1)  2007/02  [Not refereed][Not invited]

Industrial Property Rights

Research Grants & Projects

  • オキサシリン感性MRSAを用いたβラクタム薬 耐性機構の解明
    JSPS:JSPS Invitation Fellowships for Research in Japan (Long-term)
    Date (from‐to) : 2021/05 -2022/02 
    Author : Shinya Watanabe
  • 黄色ブドウ球菌性トキシックショック症候群の重篤化メカニズムの解明
    武田科学振興財団:医学系研究奨励
    Date (from‐to) : 2020 -2021 
    Author : 渡邊真弥
  • オキサシリン感性MRSAの感性化メカニズム解明によるβラクタム薬耐性の統合的理解
    日本学術振興会:科学研究費補助金 基盤(C)
    Date (from‐to) : 2019 -2021 
    Author : 渡邊真弥
  • 日本学術振興会:科学研究費補助金 若手研究(A)
    Date (from‐to) : 2015/04 -2019/03 
    Author : 渡邊真弥
  • 吸血昆虫の腸内フローラは病原体媒介能を決定する因子になるのか
    日本学術振興会:科学研究費補助金 挑戦的研究(萌芽)
    Date (from‐to) : 2018 -2019 
    Author : 加藤 大智
  • 薬剤耐性病原体に対する新規治療法に資する研究
    AMED:感染症研究革新イニシアティブ J-PRIDE
    Date (from‐to) : 2017 -2019 
    Author : 崔 龍洙
  • 皮膚細菌叢におけるゲノム交雑と耐性因子の伝播
    グラクソ・スミスクライン:GSKジャパン研究助成
    Date (from‐to) : 2015 -2016 
    Author : 渡邊真弥
  • 日本学術振興会:科学研究費補助金 若手研究(B)
    Date (from‐to) : 2013/04 -2015/03 
    Author : 渡邊真弥
  • A群レンサ球菌の劇症型感染症発症における新たな分子機構の解明
    武田科学振興財団:医学系研究奨励
    Date (from‐to) : 2014 -2015 
    Author : 渡邊真弥
  • 日本学術振興会:学術振興会特別研究員 DC2
    Date (from‐to) : 2006/04 -2008/03 
    Author : 渡邊真弥


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