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Yoshichika Arakawa

  (荒川 宜親)

Profile Information

Affiliation
School of Medicine, Fujita Health University
College of Pharmacy, Kinjo Gakuin University
Graduate School of Medicine, Nagoya University
National Institute of Infectious Diseases
名誉教授, 名古屋大学, 東海国立大学機構
Degree
医学博士(Mar, 1989, 名古屋大学)
Researcher number
10212622
J-GLOBAL ID
201101032201306103
Researcher ID
P-5997-2015
researchmap Member ID
6000030043

In the 1980s, I found that the chromosomal β‐lactamase of Klebsiella pneumoniae

LEN‐1 showed a very high similarity to the R‐plasmid‐mediated penicillinase

TEM‐1 on the amino acid sequence level, and this strongly suggested the origination

of TEM‐1 from the chromosomal penicillinases of K. pneumoniae or related

bacteria. Moreover, the chromosomal K1 β‐lactamase (KOXY) of Klebsiella oxytoca

was found to belong to the class A β‐lactamases that include LEN‐1 and TEM‐1,

although KOXY can hydrolyze cefoperazone (CPZ) like the chromosomal AmpC type

cephalosporinases of various Enterobacteriaceae that can hydrolyze several

cephalosporins including CPZ. Furthermore, my collaborators and I found plural

novel serine‐type β‐lactamases, such as MOX‐1, SHV‐24, TEM‐91, CTX‐M‐64,

CMY‐9, CMY‐19, GES‐3, GES‐4, and TLA‐3, mediated by plasmids. Besides these

serine‐type β‐lactamases, we also first identified exogenously acquired metallo‐

β‐lactamases (MBLs), IMP‐1 and SMB‐1, in imipenem‐resistant Serratia marcescens,

and the IMP‐1‐producing S. marcescens TN9106 became the index case for

carbapenemase‐producing Enterobacteriaceae. I developed the sodium mercaptoacetic

acid (SMA)‐disk test for the simple identification of MBL‐producing

bacteria. We were also the first to identify a variety of plasmid‐mediated 16S

ribosomal RNA methyltransferases, RmtA, RmtB, RmtC, and NpmA, from various

Gram‐negative bacteria that showed very high levels of resistance to a wide

range of aminoglycosides. Furthermore, we first found plasmid‐mediated quinolone

efflux pump (QepA) and fosfomycin‐inactivating enzymes (FosA3 and FosK).

We also first characterized penicillin reduced susceptible Streptococcus agalactiae (PRGBS),

macrolide‐resistant Mycoplasma pneumoniae, as well as Campylobacter jejuni, and

Helicobacter pylori, together with carbapenem‐resistant Haemophilus influenzae.

Research Interests

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Research Areas

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Major Research History

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Education

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Committee Memberships

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Awards

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Papers

 296
  • Kimura K, Nishiyama Y, Shimizu S, Wachino J, Matsui M, Suzuki S, Yamane K, Shibayama K, Arakawa Y
    Jpn J Infect Dis, 66(3) 222-225-225, 2013  
    Group B streptococcus (GBS; Streptococcus agalactiae) is a leading cause of neonatal invasive infections, and until recently, it was thought to be completely susceptible to penicillin. However, we recently identified several clinical GBS isolates with reduced penicillin susceptibility (PRGBS) whose minimum inhibitory concentrations of penicillin were >0.12 μg/ml, which is above the susceptibility breakpoint set by the Clinical and Laboratory Standards Institute. These PRGBS were isolated between 1995 and 2005 in Japan; whether these PRGBS existed in Japan before 1995 is unknown. In the study described here, we screened for PRGBS among 349 clinical GBS isolates obtained in Japan between 1977 and 2005 using the previously developed disk diffusion method for the detection of PRGBS. With this method, we selected 6 PRGBS candidates and confirmed that 1 isolate was PRGBS, using agar dilution method, including oxacillin, ceftizoxime, and penicillin-binding protein 2X (PBP2X) gene sequencing analysis. This isolate was obtained from sputum in 2005, and we could not detect PRGBS isolates before 1995 in this investigation.
  • Kimura K, Matsubara K, Yamamoto G, Shibayama K, Arakawa Y
    Jpn J Infect Dis, 66(2) 158-160-160, 2013  
    Group B streptococcus (GBS; Streptococcus agalactiae) is a leading cause of neonatal invasive infections and was believed to be fully susceptible to penicillin. However, we recently identified several clinical GBS isolates with reduced penicillin susceptibility (PRGBS), which were mainly isolated from respiratory specimens of elderly people. An investigation of both the isolation rate of PRGBS and the serotype distribution among pregnant women is crucial to decisions regarding optimal prevention and strategies for GBS treatment in neonates. We collected 141 GBS isolates from vaginal specimens of 122 pregnant women in a hospital in Kobe, Japan, from 2007 to 2008. Of the 141 GBS isolates, 139 were subjected to antimicrobial susceptibility testing based on the results of screening for PRGBS by the disk diffusion method. All 139 isolates were susceptible to penicillin G, ampicillin, cefotaxime, cefepime, and meropenem; no PRGBS isolates were detected. However, the rates of erythromycin and clindamycin resistance in the isolates were 10.1% and 5.0%, respectively, which are much higher than the values previously reported in Japan. Serotypes VI and VIII accounted for 26% of GBS; a markedly decreased percentage from the rates observed around the year 2000. These findings suggested that penicillin remains an effective means of intrapartum antibiotic prophylaxis in Japan.
  • Kimura K, Nagano N, Nagano Y, Wachino J, Shibayama K, Arakawa Y
    J Antimicrob Chemother, 68(6) 1442-1444, 2013  
  • Kimura K, Nagano N, Nagano Y, Suzuki S, Wachino J, Shibayama K, Arakawa Y
    J Antimicrob Chemother, 68(3) 539-542, 2013  
  • Ato M, Takahashi Y, Fujii H, Hashimoto S, Kaji T, Itamura S, Horiuchi Y, Arakawa Y, Tashiro M, Takemori T
    Vaccine, 31(17) 2184-2190-90, 2013  
    Infection with single strand RNA (ssRNA) viruses, such as influenza A virus, is known to induce protective acquired immune responses, including the production of neutralizing antibodies. Vaccination also causes a reduction in the number of peripheral blood leukocytes (PBL) shortly after inoculation, a result which may have undesirable adverse effects. The cellular mechanisms for this response have not been elucidated so far. Here we report that formalin-inactivated influenza A whole virus vaccine (whole virion) induces a significant decrease in PBL in mice 5-16 h after administration, whereas an ether-split vaccine (HA split) made from the same influenza virus strain does not induce a similar loss of PBL. Concordant with this reduction in the number of PBL, a rapidly induced and massive production of interferon (IFN)-α is observed when mice are injected with whole virion, but not with HA split vaccines. The role of Toll-like receptors (TLR), which are involved in signal transduction of influenza virus, and the subsequent induction of IFNα were confirmed using mice lacking TLR7, MyD-88, or IFNα/β receptor. We further demonstrated that the observed PBL loss is caused by apoptosis in an IFNα-dependent manner, and not by leukocyte redistribution due to chemokine signaling failure. These findings indicate that RNA-encapsulated whole virion vaccines can rapidly induce a loss of leukocytes from peripheral blood by apoptosis, which may modulate the subsequent immune response.
  • Yamane Kunikazu, Wachino Junichi, Suzuki Satowa, Arakawa Yoshichika
    Kawasaki medical journal, 39(3) 87-94, 2013  
    Six high-level aminoglycoside and third generated cephalosporin of cefotaxime resistance Klebsiella pneumoniae, Klebsiella oxytoca, and Escherichia coli isolated from clinical specimens in the same Japanese hospital since 2001. These 6 strains were resistant to all 4,6-disubstituted deoxystreptamine including albekacin. The results of multiplex PCR for 16S rRNA methylase and bla_<TEM>, bla_<SHV>, bla_<CTX-M> specific PCR reaction show that these strains harbor 16S rRNA methylase of rmtB and β-lactamase resistance gene of bla_<CTX-M-9> group in the same large plasmid. Sequence analysis of bla_<CTX-M-9> group PCR products shows this β-lactamase is bla_<CTX-M-14>. rmtB-harbored plasmids are classified the IncA/C by PCR and restriction pattern by EcoRI show only one or two band differences. Moreover, southern hybridization of EcoRI digested rmtB harbored plasmid by rmtB probe show the same hybridization pattern of 4.8 kbp bands. PFGE fingerprinting analysis of four K. pneumoniae revealed two fingerprinting patterns. These facts suggested that rmtB-positive starains not only spread horizontal transfer of rmtB-harbored plasmid but also clonal spread of the same strain.
  • So-Young Lee, Yeon-Joon Park, Jin Kyung Yu, Seungwon Jung, Yoonjoo Kim, Seok Hoon Jeong, Yoshichika Arakawa
    JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 67(12) 2843-2847, Dec, 2012  
    To investigate the prevalence of plasmid-mediated fosfomycin resistance determinants among extended-spectrum -lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae and their genetic environments. A total of 347 non-duplicate ESBL-producing E. coli (165) and K. pneumoniae (182) were collected. The fosfomycin MICs were determined by the agar dilution method according to CLSI guidelines. PCR was used to detect the plasmid-encoded fosfomycin resistance genes (fosA, fosA3, fosB and fosC2). For isolates harbouring plasmid-encoded fosfomycin resistance genes, sequence types (STs) were determined. The transformation experiment was performed using E. coli TOPO10 (Invitrogen, USA) as a recipient strain. With the plasmids from the transformants, plasmid replicon typing was performed and the nucleotide sequences adjacent to fosA3 were determined. The susceptibility to fosfomycin was 92.9 in E. coli and 95.2 in K. pneumoniae. Of the 21 isolates non-susceptible to fosfomycin (8 E. coli and 13 K. pneumoniae), 7 (5 E. coli and 2 K. pneumoniae) isolates harboured fosA3 and all of them co-harboured bla(CTX-M-1group) or bla(CTX-M-9group). The STs of the isolates harbouring fosA3 were diverse (E. coli: ST1, ST1, ST533, ST2 and ST86; K. pneumoniae: ST11 and ST101). The plasmid replicon types of transformants co-harbouring bla(CTX-M-1group) and bla(CTX-M-9group) were IncF and IncN, respectively. By sequence analysis, we found the common feature that the fosA3 gene, connected to bla(CTX-M) via insertion sequences, was located between two IS26 elements oriented in the opposite direction, composing an IS26-composite transposon. An IS26-composite transposon appears to be the main vehicle for dissemination of fosA3 in E. coli and K. pneumoniae of diverse clones.
  • Takahiro Nomura, Koichi Tanimoto, Keigo Shibayama, Yoshichika Arakawa, Shuhei Fujimoto, Yasuyoshi Ike, Haruyoshi Tomita
    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 56(12) 6389-6392, Dec, 2012  
    Five VanN-type vancomycin-resistant Enterococcus faecium strains were isolated from a sample of domestic chicken meat in Japan. All isolates showed low-level resistance to vancomycin (MIC, 12 mg/liter) and had the same pulsed-field gel electrophoresis profile. The vancomycin resistance was encoded on a large plasmid (160 kbp) and was expressed constitutively. The VanN-type resistance operon was identical to the first resistance operon to be reported, with the exception of a 1-bp deletion in vanT(N) and a 1-bp substitution in vanS(N).
  • Jun-ichi Wachino, Yoshichika Arakawa
    DRUG RESISTANCE UPDATES, 15(3) 133-148, Jun, 2012  
    Exogenously acquired 16S rRNA methyltransferase (16S-RMTase) genes responsible for a very high level of resistance against various aminoglycosides have been widely distributed among Enterobacteriaceae and glucose-nonfermentative microbes recovered from human and animal. The 16S-RMTases are classified into two subgroups, N7-G1405 16S-RMTases and N1-A1408 16S-RMTases, based on the mode of modification of 165 rRNA. Both MTases add the methyl group of S-adenosyl-L-methionine (SAM) to the specific nucleotides at the A-site of 16S rRNA, which interferes with aminoglycoside binding to the target. The genetic determinants responsible for 16S-RMTase production are often mediated by mobile genetic elements like transposons and further embedded into transferable plasmids or chromosome. This genetic apparatus may thus contribute to the rapid worldwide dissemination of the resistance mechanism among pathogenic microbes. More worrisome is the fact that 16S-RMTase genes are frequently associated with other antimicrobial resistance mechanisms such as NDM-1 metallo-beta-lactamase and CTX-M-type ESBLs, and some highly pathogenic microbes including Salmonella spp. have already acquired these genes. Thus far, 16S-RMTases have been reported from at least 30 countries or regions. The worldwide dissemination of 16S-RMTases is becoming a serious global concern and this implies the necessity to continue investigations on the trend of 16S-RMTases to restrict their further worldwide dissemination. (c) 2012 Elsevier Ltd. All rights reserved.
  • Noriyuki Nagano, Yukiko Nagano, Masami Toyama, Kouji Kimura, Takashi Tamura, Keigo Shibayama, Yoshichika Arakawa
    JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 67(4) 849-856, Apr, 2012  
    Multiple group B Streptococcus (GBS) isolates with reduced penicillin susceptibility (PRGBS) were recovered from several patients, hence a probable nosocomial transmission of PRGBS in a hospital setting was suspected. Ten PRGBS recovered from eight patients in a general hospital were characterized. Sequence analysis of genes for penicillin-binding proteins (PBPs) and quinolone resistance-determining regions (QRDRs) of gyrA, gyrB and parC was performed, and the macrolide resistance genes were detected by PCR. Genetic relatedness among the isolates was examined by PFGE and multilocus sequence typing. All the PRGBS had the key amino acid substitution V405A, together with F395L, R433H, H438Y and G648A in PBP 2X and T567I in PBP 2B. A 23S rRNA methylase gene, erm(B), was also found in all 10 PRGBS strains. PFGE analysis revealed considerable genetic relatedness among the isolates. Isolates of pulsotype I were obtained from four patients in ward A and one patient in ward B, while isolates of pulsotypes II and III were obtained from two patients in ward B and one patient in ward C, respectively. Isolates of pulsotype I were resistant to levofloxacin (MIC 8 mg/L) and had the following amino acid substitutions in the QRDRs: S81L in GyrA, E476K in GyrB and S79Y in ParC. However, pulsotype II strains resistant to levofloxacin (MIC 8 mg/L) had no change in GyrA, but changes in GyrB (E476K) and ParC (S79Y). All 10 PRGBS strains belonged to serotype VI and ST458 (where ST stands for sequence type). This is the first description of the nosocomial spread of multidrug-resistant PRGBS strains belonging to the genetic lineage ST458.
  • Nao Otsuka, Hyun-Ja Han, Hiromi Toyoizumi-Ajisaka, Yukitsugu Nakamura, Yoshichika Arakawa, Keigo Shibayama, Kazunari Kamachi
    PLOS ONE, 7(2) e31985, Feb, 2012  
    The adhesin pertactin (Prn) is one of the major virulence factors of Bordetella pertussis, the etiological agent of whooping cough. However, a significant prevalence of Prn-deficient (Prn(-)) B. pertussis was observed in Japan. The Prn(-) isolate was first discovered in 1997, and 33 (27%) Prn(-) isolates were identified among 121 B. pertussis isolates collected from 1990 to 2009. Sequence analysis revealed that all the Prn(-) isolates harbor exclusively the vaccine-type prn1 allele and that loss of Prn expression is caused by 2 different mutations: an 84-bp deletion of the prn signal sequence (prn1 Delta SS, n = 24) and an IS481 insertion in prn1 (prn1::IS481, n = 9). The frequency of Prn(-) isolates, notably those harboring prn1 Delta SS, significantly increased since the early 2000s, and Prn(-) isolates were subsequently found nationwide. Multilocus variable-number tandem repeat analysis (MLVA) revealed that 24 (73%) of 33 Prn(-) isolates belong to MLVA-186, and 6 and 3 Prn(-) isolates belong to MLVA-194 and MLVA-226, respectively. The 3 MLVA types are phylogenetically closely related, suggesting that the 2 Prn(-) clinical strains (harboring prn1 Delta SS and prn1::IS481) have clonally expanded in Japan. Growth competition assays in vitro also demonstrated that Prn(-) isolates have a higher growth potential than the Prn(+) back-mutants from which they were derived. Our observations suggested that human host factors (genetic factors and immune status) that select for Prn(-) strains have arisen and that Prn expression is not essential for fitness under these conditions.
  • Satowa Suzuki, Kunikazu Yamane, Jun-ichi Wachino, Mari Matsui, Toshifumi Konda, Yoshichika Arakawa
    Nihon rinsho. Japanese journal of clinical medicine, 70(2) 187-91, Feb, 2012  Peer-reviewed
    In 2010, a three months survey of multidrug-resistant Enterobacteriaceae was conducted by Ministry of Health, Labour and Welfare of Japan. A total of 153 isolates were obtained through this survey and we performed PCR using the NDM-1 type, KPC type, IMP-1 type, IMP-2 type and VIM-2 type carbapenemase genes specific primers. Of 153 analyzed isolates, 72 (47.1%) were positive for IMP-1 type bla(IMP), and two isolates from two patients were positive for bla(NDM-1). None of those patients had traveled abroad. Two isolates from a single patient who had traveled and hospitalized in abroad were positive for bla(KPC). 77 (50.3%) isolates were all negative for those five carbapenemase genes. It was shown that IMP-1 type is the most predominant carbapenemase gene among Enterobacteriaceae in Japan.
  • Wachino J, Yamaguchi Y, Mori S, Yamagata Y, Arakawa Y, Shibayama K
    Acta Crystallogr Sect F Struct Biol Cryst Commun, 68(3) 343-346, 2012  
  • Jun-ichi Wachino, Hiroyuki Yoshida, Kunikazu Yamane, Satowa Suzuki, Mari Matsui, Takuya Yamagishi, Atsuko Tsutsui, Toshifumi Konda, Keigo Shibayama, Yoshichika Arakawa
    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 55(11) 5143-5149, Nov, 2011  
    A carbapenem-resistant Serratia marcescens strain, 10mdr148, was identified in a Japanese hospital in 2010. The carbapenem resistance of this strain was attributed to the production of a novel metallo-beta-lactamase (MBL), named SMB-1 (Serratia metallo-beta-lactamase). SMB-1 possessed a zinc binding motif, H(Q) XHXDH (residues 116 to 121), H196, and H263 and was categorized as a member of subclass B3 MBL. SMB-1 has 75% amino acid identity with the most closely related MBL, AMO1, of uncultured bacterium, recently identified through the metagenomic analysis of apple orchard soil. The introduction of bla(SMB-1) into Escherichia coli conferred resistance to a variety of beta-lactam antibiotics, penicillins, cephalosporins, and carbapenems, but not aztreonam, a resistance pattern consistent with those of other MBLs. SMB-1 demonstrated high k(cat) values of &gt;500 s(-1) for carbapenems, resulting in the highest hydrolyzing efficiency (k(cat)/K(m)) among the agents tested. The hydrolyzing activity of SMB-1 was well inhibited by chelating agents. The bla(SMB-1) gene was located on the chromosome of S. marcescens strain 10mdr148 and at the 3&apos; end of the ISCR1 element in complex with a typical class 1 integron carrying aac(6&apos;)-Ib and catB3 gene cassettes. Downstream of bla(SMB-1), the second copy of the 3&apos; conserved segment and ISCR1 were found. To our knowledge, this is the first subclass B3 MBL gene associated with an ISCR1 element identified in an Enterobacteriaceae clinical isolate. A variety of antibiotic resistance genes embedded with ISCR1 have been widely spread among Enterobacteriaceae clinical isolates, thus the further dissemination of bla(SMB-1) mediated by ISCR1 transposition activity may become a future concern.
  • Kouji Kimura, Noriyuki Nagano, Yukiko Nagano, Jun-ichi Wachino, Satowa Suzuki, Keigo Shibayama, Yoshichika Arakawa
    JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY, 66(11) 2460-2464, Nov, 2011  
    Background: Although group B Streptococcus (GBS; i.e. Streptococcus agalactiae) has been considered to be uniformly susceptible to beta-lactams, GBS isolates with reduced penicillin susceptibility (PRGBS) have been reported from Japan and North America. In this study, PRGBS from Japan were characterized by multilocus sequence typing (MLST) and the results compared with data on PRGBS reported from the USA. Methods: Twenty-eight clinical isolates of PRGBS recovered in Japan (including 22 isolates previously analysed by PFGE) were analysed by MLST and eBURST (http://eburst.mlst.net/). Results: Twenty-three isolates were found to belong to the sequence type 1 (ST1) group (11 ST458, 7 ST1, 3 ST297, 1 ST358 and 1 ST4), while the remaining 5 isolates formed the ST23 group. Among 11 ST458 and 7 ST1 isolates, 9 and 4 were serotype VI, respectively, indicating a probable correlation between the ST1 group and serotype VI for PRGBS in Japan. Conclusions: PRGBS in Japan could be classified into at least two ST groups, ST1 and ST23, which are genetically different from the ST19 PRGBS isolated in the USA, though five allele variations were seen between ST1 and ST19, implying a slight genetic relatedness.
  • Yoshihiro Yamaguchi, Shijia Ding, Emi Murakami, Kayo Imamura, Sachiko Fuchigami, Ryo Hashiguchi, Katsuhide Yutani, Hiromasa Mori, Shinnichiro Suzuki, Yoshichika Arakawa, Hiromasa Kurosaki
    CHEMBIOCHEM, 12(13) 1979-1983, Sep, 2011  
  • Tsuyoshi Sekizuka, Mari Matsui, Kunikazu Yamane, Fumihiko Takeuchi, Makoto Ohnishi, Akira Hishinuma, Yoshichika Arakawa, Makoto Kuroda
    PLOS ONE, 6(9) e25534, Sep, 2011  
    The complete sequence of the plasmid pNDM-1_Dok01 carrying New Delhi metallo-beta-lactamase (NDM-1) was determined by whole genome shotgun sequencing using Escherichia coli strain NDM-1_Dok01 (multilocus sequence typing type: ST38) and the transconjugant E. coli DH10B. The plasmid is an IncA/C incompatibility type composed of 225 predicted coding sequences in 195.5 kb and partially shares a sequence with bla(CMY-2)-positive IncA/C plasmids such as E. coli AR060302 pAR060302 (166.5 kb) and Salmonella enterica serovar Newport pSN254 (176.4 kb). The bla(NDM-1) gene in pNDM-1_Dok01 is terminally flanked by two IS903 elements that are distinct from those of the other characterized NDM-1 plasmids, suggesting that the bla(NDM-1) gene has been broadly transposed, together with various mobile elements, as a cassette gene. The chaperonin groES and groEL genes were identified in the bla(NDM-1)-related composite transposon, and phylogenetic analysis and guanine-cytosine content (GC) percentage showed similarities to the homologs of plant pathogens such as Pseudoxanthomonas and Xanthomonas spp., implying that plant pathogens are the potential source of the bla(NDM-1) gene. The complete sequence of pNDM-1_Dok01 suggests that the bla(NDM-1) gene was acquired by a novel composite transposon on an extensively disseminated IncA/C plasmid and transferred to the E. coli ST38 isolate.
  • A. Tsutsui, S. Suzuki, K. Yamane, M. Matsui, T. Konda, E. Marui, K. Takahashi, Y. Arakawa
    JOURNAL OF HOSPITAL INFECTION, 78(4) 317-322, Aug, 2011  
    An outbreak of multidrug-resistant (MDR) Pseudomonas aeruginosa occurred in an acute care hospital in Japan, which lasted for more than three years. During January 2006 to June 2009, 59 hospitalised patients with MDR P. aeruginosa were mainly detected by urine culture in the first half, whereas isolation from respiratory tract samples became dominant in the latter half of the outbreak. Non-duplicate MDR P. aeruginosa isolates were available from 51 patients and all isolates were positive for bla(VIM-2). Pulsed-field gel electrophoresis (PFGE) analysis categorised the isolates into three major clusters; types A, B and C with eight, 19 and 21 isolates, respectively. The outbreak started with patients harbouring PFGE type A strains, followed by type B, and type C strains. Multivariate analysis demonstrated that patients with PFGE type C strains were more likely to be detected by respiratory tract samples (odds ratio: 11.87; 95% confidence interval: 1.21-116.86). Improved aseptic urethral catheter care controlled PFGE type A and type B strains and improvement in respiratory care procedures finally contained the transmission of PFGE type C strains. (C) 2011 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.
  • Yoshihiro Yamaguchi, Kayo Imamura, Ako Sasao, Emi Murakami, Yoshichika Arakawa, Hiromasa Kurosaki
    MEDCHEMCOMM, 2(8) 720-725, Aug, 2011  
    IMP-1 metallo-beta-lactamase is a dinuclear Zn(II) enzyme that catalyzes the hydrolysis and inactivation of most beta-lactams including carbapenems, and is involved in one of the mechanisms for generating clinical resistance to antibiotics in pathogenic bacteria. We investigated the metal preferences of Zn(II) and Co(II) for the apo-enzyme of IMP-1 metallo-beta-lactamase, apo-IMP-1, which contains a dinuclear metal binding site (the Zn1 and Zn2 sites), by UV-visible spectroscopy. The UV-visible spectrum of apo-IMP-1 containing 1 equiv. of Co(II) and 1 equiv. of Zn(II) showed a high preference of Zn(II) for the Zn1 site compared to Co(II). Moreover, Zn(II) bound more strongly to the Zn2 site than Co(II). The interaction of IMP-I metallo-beta-lactamase with mercaptoacetic acid was also investigated using CO(II)-substituted IMP-1 and UV-visible spectroscopy. Possible metal binding modes of Co(II) or Zn(II) to the dinuclear metal binding site in apo-IMP-1 and of mercaptoacetic acid to CO(II)-substituted IMP-1 are proposed.
  • Haru Kato, Yoshichika Arakawa
    JOURNAL OF MEDICAL MICROBIOLOGY, 60(8) 1126-1130, Aug, 2011  
    The loop-mediated isothermal amplification (LAMP) assay detecting the slpA gene of slpA sequence type gc8 (slpA-gc8) was established for the identification of a hypervirulent Clostridium difficile strain, PCR ribotype 027. Of 107 isolates examined, 27 belonging to PCR ribotype 027 were all positive for the LAMP assay. The remaining 80 isolates were typed into 47 different PCR ribotypes other than type 027, and were negative for the LAMP assay with the exception of two isolates. The sensitivity and specificity of the LAMP method for identification of PCR ribotype 027 were 100% and 98%, respectively. The LAMP assay detecting slpA-gc8 is a reliable tool for the identification of PCR ribotype 027 C. difficile. This simple and rapid method will contribute to detection of the hypervirulent strain.
  • Shigetarou Mori, Keigo Shibayama, Jun-Ichi Wachino, Yoshichika Arakawa
    JOURNAL OF MOLECULAR BIOLOGY, 410(1) 93-104, Jul, 2011  
    Rv2613c is a diadenosine 5',5'''-P-1,P-4-tetraphosphate (Ap(4)A) phosphorylase from Mycobacterium tuberculosis H37Rv. Sequence analysis suggests that Rv2613c belongs to the histidine triad (HIT) motif superfamily, which includes HIT family diadenosine polyphosphate (Ap(n)A) hydrolases and Ap(4)A phosphorylases. However, the amino acid sequence of Rv2613c is more similar to that of HIT family Ap(n)A hydrolases than to that of typical Ap(4)A phosphorylases. Here, we report the crystal structure of Ry2613c, which is the first structure of a protein with Ap(n)A phosphorylase activity, and characterized the structural basis of its catalytic activity. Our results showed that the structure of Rv2613c is similar to those of other HIT superfamily proteins. However, Asn139, Gly146, and Ser147 in the active site of Ry2613c replace the corresponding Gln, Gln, and Thr residues that are normally found in HIT family Ap(n)A hydrolases. Furthermore, analyses of Rv2613c mutants revealed that Asn139, Gly146, and Ser147 are important active-site residues and that Asn139 has a critical role in catalysis. The position of Gly146 might influence the phosphorylase activity. In addition, the tetrameric structure of Rv2613c and the presence of Trp160 might be essential for the formation of the Ap(4)A binding site. These structural insights into Rv2613c may facilitate the development of novel structure-based inhibitors for treating tuberculosis. (C) 2011 Elsevier Ltd. All rights reserved.
  • Jun-ichi Wachino, Kunikazu Yamane, Yoshichika Arakawa
    JOURNAL OF CLINICAL MICROBIOLOGY, 49(6) 2378-2379, Jun, 2011  
  • Hyun-Ja Han, Asaomi Kuwae, Akio Abe, Yoshichika Arakawa, Kazunari Kamachi
    PLOS ONE, 6(3) e17797, Mar, 2011  
    Background: Bordetella pertussis is the primary etiologic agent of the disease pertussis. Universal immunization programs have contributed to a significant reduction in morbidity and mortality of pertussis; however, incidence of the disease, especially in adolescents and adults, has increased in several countries despite high vaccination coverage. During the last three decades, strains of Bordetella pertussis in circulation have shifted from the vaccine-type to the nonvaccine-type in many countries. A comparative proteomic analysis of the strains was performed to identify protein(s) involved in the type shift. Methodology/Principal Finding: Proteomic analysis identified one differentially expressed protein in the B. pertussis strains: the type III cytotoxic effector protein BteA, which is responsible for host cell death in Bordetella bronchiseptica infections. Immunoblot analysis confirmed the prominent expression of BteA protein in the nonvaccine-type strains but not in the vaccine-type strains. Sequence analysis of the vaccine-type strains revealed an IS481 insertion in the 5&apos; untranslated region of bteA, -136 bp upstream of the bteA start codon. A high level of bteA transcripts from the IS481 promoter was detected in the vaccine-type strains, indicating that the transcript might be an untranslatable form. Furthermore, BteA mutant studies demonstrated that BteA expression in the vaccine-type strains is down-regulated by the IS481 insertion. Conclusion/Significance: The cytotoxic effector BteA protein is expressed at higher levels in B. pertussis nonvaccine-type strains than in vaccine-type strains. This type-dependent expression is due to an insertion of IS481 in B. pertussis clinical strains, suggesting that augmented expression of BteA protein might play a key role in the type shift of B. pertussis.
  • Y. Nakamura, K. Kamachi, H. Toyoizumi-Ajisaka, N. Otsuka, R. Saito, J. Tsuruoka, T. Katsuta, N. Nakajima, K. Okada, T. Kato, Y. Arakawa
    CLINICAL MICROBIOLOGY AND INFECTION, 17(3) 365-370, Mar, 2011  
    P&gt;Bordetella pertussis is the aetiologic agent of whooping cough, a common cause of severe respiratory illness in children and prolonged mild cough in adults. To understand some of the reasons for differences in clinical symptoms between adults and children, we measured B. pertussis DNA loads in nasopharyngeal swabs (NPS) from 19 adults and 40 children (including 14 infants) by quantitative IS481 real-time PCR. All cases had been pre-diagnosed with the B. pertussis-specific loop-mediated isothermal amplification method. The mean PCR threshold cycles for adult and child NPS were 34.9 and 27.1, respectively, indicating a significantly lower B. pertussis DNA load in adults than in children (p &lt; 0.001). Moreover, adults had very low DNA loads during both early and later stages of the disease. When corresponding bacterial loads in NPS were calculated for B. pertussis Tohama cells using a standard curve, the mean number of bacterial cells taken with a rayon-tipped swab from an adult, older child and infant was estimated to be 320 (95% CI 120-910), 2.1 x 104 (95% CI 5.3 x 103 to 8.3 x 104) and 1.1 x 106 cells (95% CI 1.2 x 105 to 8.9 x 106), respectively. This indicates that the B. pertussis load in NPS is closely correlated with patient age. Our observations suggest that adult pertussis is characterized by a lower bacterial load in the nasopharynx, resulting in milder symptoms and negative cultures.
  • Shibayama K, Takeuchi H, Wachino J, Mori S, Arakawa Y
    Microbiol Immunol, 55(6) 408-417-417, 2011  
  • Ohno H, Ogata Y, Suguro H, Yokota S, Watanabe A, Kamei K, Yamagoe S, Ishida-Okawara A, Kaneko Y, Horino A, Yamane K, Tsuji T, Nagata N, Hasegawa H, Arakawa Y, Sata T, Miyazaki Y
    Internal Medicine, 49(5) 491-495-495, 2010  
    Histoplasmosis, caused by Histoplasma capsulatum, is an endemic mycosis in many countries of the world except for Japan. Outbreaks of histoplasmosis among Japanese people are very rare and are mainly imported by travelers. We report an outbreak of histoplasmosis among healthy Japanese people who traveled to a resort area in Southeast Asia. Three young Japanese women traveled to Langkawi island, Malaysia and stayed on the island for five days without visiting caves, a known reservoir of H. capsulatum. All three individuals developed flu-like symptoms with multiple nodule shadows on chest X rays or chest CT scans at around ten days after their return to Japan. Serum samples obtained from the three subjects were positive for anti-Histoplasma antibody and specific PCR for H. capsulatum on lung biopsy specimens and the serum from one patient was positive. The clinical course of all three patients improved without the use of anti-fungal agents and no recurrence has been confirmed. Clinical attendants should consider histoplasmosis when they see patients with flu-like symptoms with abnormal chest X-rays after visiting H. capsulatum endemic areas, especially Southeast Asia.<br>
  • Komiya T, Seto Y, De Zoysa A, Iwaki M, Hatanaka A, Tsunoda A, Arakawa Y, Kozaki S, Takahashi M
    : Journal of Medical Microbiology, 59(12) 1497-1504, 2010  
  • Wachino J, Shibayama K, Kimura K, Yamane K, Suzuki S, Arakawa Y
    FEMS Microbiol Lett, 311(1) 56-60-60, 2010  
  • Minauchi K, Takahashi S, Sakai T, Kondo M, Shibayama K, Arakawa Y, Mukai M
    Intern Med, 49(16) 1733-1739-1739, 2010  
    Background We encountered 15 cases of Helicobacter cinaedi (H. cinaedi) infection between March and July 2008.<br> Patient, Method, and Result The underlying diseases were hematological malignancies in a majority of cases, many of which received chemotherapy. All patients had a fever. The fever was followed by cellulitis in three, a skin rash in six, pain in the lower limbs in three, and diarrhea in three cases. We analyzed the bacterial 23S rRNA genes. The fifteen strains were divided according to base sequence into Groups A, B, and C, respectively. All four cases in Group A were women and all ten in Group C were men, indicating that the gender of the patient corresponded precisely to the genotypes of the separated bacilli in these two groups. These findings also suggested the strong possibility of nosocomial spread.<br> Conclusion It is highly likely that H. cinaedi infections have been overlooked due to the difficulties encountered in culturing the bacterium. The possibility of septicemia caused by H. cinaedi should be suspected especially in immunocompromised patients such as those undergoing chemotherapy, with symptoms such as fever, rash, arthritis, cellulitis, leg pain, and other systemic or local symptoms.<br>
  • Wachino J, Shibayama K, Suzuki S, Yamane K, Mori S, Arakawa Y
    Helicobacter, 15(3) 184-192-192, 2010  
  • Iwaki M, Komiya T, Yamamoto A, Ishiwa A, Nagata N, Arakawa Y, Takahashi M
    Infect Immun, 78(9) 3791-800, 2010  
  • Kawamura-Sato K, Wachino, J, Kondo T, Ito H, Arakawa Y
    J Antimicrob Chemother, 65(9) 1975-1983, 2010  
  • Kuroda M, Katano H, Nakajima N, Tobiume M, Ainai A, Sekizuka T, Hasegawa H, Tashiro M, Sasaki Y, Arakawa Y, Hata S, Watanabe M, Sata T
    PLoS One, 5(4) e10256, 2010  
  • Wachino J, Yamane K, Suzuki S, Kimura K, Arakawa Y
    Antimicrob Agents Chemother, 54(7) 3061-3064-3064, 2010  
  • Yamaguchi Y, Takashio N, Wachino J, Yamagata Y, Arakawa Y, Matsuda K, Kurosaki H
    J Biochem, 147(6) 905-915, 2010  
  • Shigetarou Mori, Keigo Shibayama, Jun Ichi Wachino, Yoshichika Arakawa
    Acta Crystallographica Section F: Structural Biology and Crystallization Communications, 66(3) 279-281, 2010  
    A novel diadenosine 5′,5′′′-P 1,P 4-tetraphosphate (Ap4A) phosphorylase (Rv2613c) from Mycobacterium tuberculosis H37Rv has been crystallized by the sitting-drop vapour-diffusion method. The crystal belonged to space group C2, with unit-cell parameters a = 101.5, b = 63.6, c = 79.1 Å, Β = 110.9°. The diffraction of the crystals extended to 1.9 Å resolution. The asymmetric unit is expected to contain two molecules of Rv2613c, with a corresponding crystal volume per protein weight (VM) of 2.41 Å3 Da-1 and a solvent content of 49.1%. This is the first report of a crystal of Ap4A phosphorylase. © 2010 International Union of Crystallography All rights reserved.
  • Kato H, Kato H, Ito Y, Akahane T, Izumida S, Yokoyama T, Kaji C, Arakawa Y
    J Med Microbiol, 59(5) 556-562, 2010  
  • Kamachi K, Fukuda T, Han HJ, Toyoizumi-Ajisaka H, Mochida K, Konda T, Horiuchi Y, Arakawa Y
    Biologicals, 38(2) 290-293-3, 2010  
    In Japan, the Bordetella pertussis strain Tohama provided by the National Institute of Health, Japan has been used for the production of acellular pertussis (aP) vaccines since 1981. In the present study, in order to verify the genetic consistency of B. pertussis vaccine seed strains, we analyzed the genetic properties of the working seeds obtained from five Japanese vaccine manufacturers, and compared them with those of B. pertussis Tohama reference strains (NIID L-7 and ATCC BAA-589). Genetic analyses with pulsed-field gel electrophoresis and allele typing showed 100% genetic identity among the five seed strains and the Tohama reference strains. In addition, Southern blot analyses revealed the absence of four orthologous genes (BB0537, BB0920, BB1149 and BB4885), which are specifically absent in the strain Tohama, and in the genome of all seed strains tested, suggesting that the regions of difference (RD11-RD14) are absent in their genomes. Consequently, no genetic difference was observed among the working seeds and Tohama reference strains. Our observations indicate that B. pertussis seed strains for Japanese aP vaccine production are genetically comparable with B. pertussis Tohama.
  • Mori S, Shibayama K, Wachino J, Arakawa Y
    Protein Expr Purif, 69(1) 99-105, 2010  
  • Kunikazu Yamane, Yoshichika Arakawa
    Japanese Journal of Anesthesiology, 59(1) 4-16, Jan, 2010  Peer-reviewed
    The discovery of penicillin in 1928 was followed by the discovery and synthesis of various kinds of antimicrobial agents such as quinolone, aminogycoside, macrolide, tetracyclone, and oxazolidinone. These discoveries dramatically decreased the mortality rate due to infectious diseases. However, bacteria have also acquired antimicrobial-resistance genes or changed their own genes to oppose these antimicrobial agents, and now drug-resistant bacteria are becoming a serious clinical concern. Today, contagious diseases must be treated with the limited number of effective antimicrobial agents available. Infection control measures are required to prevent the spread of resistant bacteria in the clinical environment, and we must also increase our understanding of the drug-resistant mechanisms of bacteria. In this issue we wish to introduce the recent worldwide trend in antimicrobial-resistant bacteria, especially multidrug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus, and multidrug-resistant Pseudomonas aeruginosa, along with recently-discovered antimicrobial-resistant systems.
  • Nagano N, Kimura K, Nagano Y, Yakumaru H, Arakawa Y
    J Antimicrob Chemother, 64(6) 1326-1328-1328, 2009  
  • Kimura K, Wachino JI, Kurokawa H, Suzuki S, Yamane K, Shibata N, Arakawa Y
    J Clin Microbiol, 47(12) 4154-4157-4157, 2009  
  • Honma Y, Yoshii Y, Watanabe Y, Aoki N, Komiya T, Iwaki M, Arai H, Arakawa Y, Takahashi M, Kimura H
    Jpn J Infect Dis, 62(4) 327-329-329, 2009  
  • Ohkura T, Yamada K, Okamoto A, Baba H, Ike Y, Arakawa Y, Hasegawa T, Ohta M
    J Med Microbiol, 58(10) 1329-1336-1336, 2009  
  • Yamaguchi Y, Sato G, Yamagata Y, Doi Y, Wachino J, Arakawa Y, Matsuda K, Kurosaki H
    Acta Crystallogr Sect F Struct Biol Cryst Commun, 65(6) 540-543, 2009  
  • Park YJ, Yu JK, Kim SI, Lee K, Arakawa Y
    Ann Clin Lab Sci, 39(1) 55-59-59, 2009  
  • Piao Z, Shibayama K, Mori S, Wachino J, Arakawa Y
    FEMS Microbiol Lett, 291(2) 216-221, 2009  
  • Suzuki S, Shibata N, Yamane K, Wachino J, Ito K, Arakawa Y
    J Antimicrob Chemother, 63(1) 72-79-79, 2009  
  • Nagano Y, Nagano N, Wachino J, Ishikawa K, Arakawa Y
    Antimicrob Agents Chemother, 53(1) 69-74, 2009  
  • Kamano H, Mori T, Maeta H, Kishimoto N, Katami T, Sato M, Kamachi K, Arakawa Y
    International Journal of Infectious Diseases, 12 E463-E464, 2008  

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  • 1989 - Present
    医学細菌学、病原細菌学、薬剤耐性菌等  (名古屋大学 [医、保健、工]、群馬大学 [医]、千葉大学 [薬]、東京薬科大学 [薬]、愛知学院大学 [歯・薬]、岐阜薬科大学 [薬]、愛知医科大学[医]、 他)

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