TAKAHASHI Satoshi

写真a

Affiliation

School of Medicine, Department of Clinical Laboratory Medicine

Job title

Professor
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Education 【 display / non-display 】

  • 2015
    -
    Now

    Sapporo Medical University  

  • 1992
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    2015

    Sapporo Medical University  

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    1992

    Sapporo Medical University  

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Degree 【 display / non-display 】

  • 1, Bactericidal effect of levofloxacin on strains with equal susceptibility in an in vitro urinary bladder model. 2, Changes in susceptibility of Pseudomonas aeruginosa to gatifloxacin and carbapenem in an in vitro urinary bladder model.

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Professional Memberships 【 display / non-display 】

  • 2015
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    Now

    Japanese Society of Laboratory Medicine

  • 2015
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    Now

    The Japan Association for Clinical Laboratory Science

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    American Sexually Transmitted Diseases Association

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    Japanese Association for Infectious Diseases

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    Japanese Society of Endourology and ESWL

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Research Areas 【 display / non-display 】

  • Life sciences   Infectious disease  

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Affiliation 【 display / non-display 】

  • Sapporo Medical University   School of Medicine, Department of Infection Control and Laboratory Medicine  

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Research Interests 【 display / non-display 】

  • Urinary tract infection, sexually transmitted infection, clinical laboratory medicine

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Papers 【 display / non-display 】

  • High prevalence of colistin heteroresistance in specific species and lineages of Enterobacter cloacae complex derived from human clinical specimens.

    Shota Fukuzawa, Toyotaka Sato, Kotaro Aoki, Soh Yamamoto, Noriko Ogasawara, Chie Nakajima, Yasuhiko Suzuki, Motohiro Horiuchi, Satoshi Takahashi, Shin-Ichi Yokota

    Annals of clinical microbiology and antimicrobials   22 ( 1 ) 60 - 60  2023.07  [International journal]

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    BACKGROUND: Colistin (CST) is a last-line drug for multidrug-resistant Gram-negative bacterial infections. CST-heteroresistant Enterobacter cloacae complex (ECC) has been isolated. However, integrated analysis of epidemiology and resistance mechanisms based on the complete ECC species identification has not been performed. METHODS: Clinical isolates identified as "E. cloacae complex" by MALDI-TOF MS Biotyper Compass in a university hospital in Japan were analyzed. Minimum inhibitory concentrations of CST were determined by the broth microdilution method. The population analysis profiling (PAP) was performed for detecting the heteroresistant phenotype. The heat shock protein 60 (hsp60) cluster was determined from its partial nucleotide sequence. From the data of whole-genome sequencing, average nucleotide identity (ANI) for determining ECC species, multilocus sequence type, core genome single-nucleotide-polymorphism-based phylogenetic analysis were performed. phoPQ-, eptA-, and arnT-deleted mutants were established to evaluate the mechanism underlying colistin heteroresistance. The arnT mRNA expression levels were determined by reverse transcription quantitative PCR. RESULTS: Thirty-eight CST-resistant isolates, all of which exhibited the heteroresistant phenotype by PAP, were found from 138 ECC clinical isolates (27.5%). The prevalence of CST-resistant isolates did not significantly differ among the origin of specimens (29.0%, 27.8%, and 20.2% for respiratory, urine, and blood specimens, respectively). hsp60 clusters, core genome phylogeny, and ANI revealed that the CST-heteroresistant isolates were found in all or most of Enterobacter roggenkampii (hsp60 cluster IV), Enterobacter kobei (cluster II), Enterobacter chuandaensis (clusters III and IX), and Enterobacter cloacae subspecies (clusters XI and XII). No heteroresistant isolates were found in Enterobacter hormaechei subspecies (clusters VIII, VI, and III) and Enterobacter ludwigii (cluster V). CST-induced mRNA upregulation of arnT, which encodes 4-amino-4-deoxy-L-arabinose transferase, was observed in the CST-heteroresistant isolates, and it is mediated by phoPQ pathway. Isolates possessing mcr-9 and mcr-10 (3.6% and 5.6% of total ECC isolates, respectively) exhibited similar CST susceptibility and PAP compared with mcr-negative isolates. CONCLUSIONS: Significant prevalence (approximately 28%) of CST heteroresistance is observed in ECC clinical isolates, and they are accumulated in specific species and lineages. Heteroresistance is occurred by upregulation of arnT mRNA induced by CST. Acquisition of mcr genes contributes less to CST resistance in ECC.

    DOI PubMed

  • Colistin-resistant bacteria poses few risks under physiological conditions

    Soh Yamamoto, Masaru Usui, Noriko Ogasawara, Wataru Hayashi, Masato Suzuki, Noriyuki Nagano, Chie Nakajima, Yasuhiko Suzuki, Motohiro Horiuchi, Satoshi Takahashi, Shin-ichi Yokota, Yutaka Tamura, Toyotaka Sato

    Research Square ( Research Square Platform LLC )   2023.06

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    Abstract Globally, 5.0 million people die annually from infections associated with antimicrobial-resistant bacteria, most commonly Escherichia coli1. As colistin is a last-resort antibiotic for multidrug-resistant bacterial infections, the global spread of plasmid-mediated colistin resistance genes (mcr) gene is considered a major public health risk2-4. However, the actual health risks of colistin resistance in hazardous bacteria have never been evaluated under physiological conditions. Here, we show that the fitness/virulence and colistin resistance of the pandemic multidrug-resistant E. coli clone ST1315 very depending on the acquired colistin resistance determinants and differ between physiological and in vitro conditions. The fitness/virulence of ST131 was unaffected by chromosomal-gene (pmrB) mutations or the acquisition of mcr-5-harbouring plasmids in mouse models. However, the acquisition of mcr-1- or mcr-3-harbouring plasmids attenuated fitness/virulence and promoted colistin susceptibility in human serum. We identified two virulence attenuation factors (vafA and vafB) on the pIncI2_mcr-1 plasmid that hijacked the ST131 transcriptome and inhibited nucleotide synthesis, attenuating colistin resistance. Our results demonstrate that colistin resistance poses much less of a threat than believed6,7. We suggest that “nonresistance genes,” rather than resistance genes, are important antimicrobial resistance determinants for human health because they determine fitness/virulence and ultimately antimicrobial susceptibility under physiological conditions.

    DOI

  • Pseudo-outbreak of Mycobacterium lentiflavum at a general hospital in Japan.

    Yutaro Nagano, Koji Kuronuma, Yasuo Kitamura, Kanami Nagano, Hayato Yabe, Sayaka Kudo, Toyotaka Sato, Shinya Nirasawa, Mami Nakae, Motohiro Horiuchi, Shin-Ichi Yokota, Yoshihiro Fujiya, Atsushi Saito, Satoshi Takahashi, Hirofumi Chiba

    Infection control and hospital epidemiology     1 - 7  2023.04  [International journal]

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    BACKGROUND: Mycobacterium lentiflavum is a slow-growing nontuberculous mycobacterium that is widely distributed in soil and water systems, but it is sometimes pathogenic to humans. Although cases of M. lentiflavum infections are rare, 22 isolates of M. lentiflavum were identified at a single hospital in Japan. We suspected a nosocomial outbreak; thus, we conducted transmission pattern and genotype analyses. METHODS: Cases of M. lentiflavum isolated at Kushiro City General Hospital in Japan between May 2020 and April 2021 were analyzed. The patient samples and environmental culture specimens underwent whole-genome sequencing (WGS). Additionally, we retrospectively collected clinical data from patient medical records. RESULTS: Altogether, 22 isolates of M. lentiflavum were identified from sputum and bronchoalveolar lavage samples. Clinically, the instances with M. lentiflavum isolates were considered contaminants. In the WGS analysis, 19 specimens, including 18 patient samples and 1 environmental culture from the hospital's faucet, showed genetic similarity. The frequency of M. lentiflavum isolation decreased after we prohibited the use of taps where M. lentiflavum was isolated. CONCLUSIONS: WGS analysis identified that the cause of M. lentiflavum pseudo-outbreak was the water used for patient examinations, including bronchoscopy.

    DOI PubMed

  • Corrigendum to 'Clonal/subclonal changes and accumulation of CTX-M-type β-lactamase genes in fluoroquinolone-resistant Escherichia coli ST131 and ST1193 strains isolated during the past 12 years, Japan' [Journal of Global Antimicrobial Resistance 27 (2021) 150-155].

    Yukari Fukushima, Toyotaka Sato, Naoyuki Tsukamoto, Chie Nakajima, Yasuhiko Suzuki, Satoshi Takahashi, Shin-Ichi Yokota

    Journal of global antimicrobial resistance   32   195 - 195  2023.03  [International journal]

    DOI PubMed

  • Analysis of diagnostic performance and factors causing nonspecific reactions in SARS-CoV-2 rapid antigen detection tests.

    Natsuki Narumi, Takashi Kondo, Yuki Sato, Yuki Katayama, Shinya Nirasawa, Masachika Saeki, Yuki Yakuwa, Yoshihiro Fujiya, Koji Kuronuma, Satoshi Takahashi

    Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy   29 ( 2 ) 157 - 162  2023.02  [International journal]

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    INTRODUCTION: Early diagnosis and appropriate infection control are important to prevent the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this study, we aimed to assess the diagnostic performance of SARS-CoV-2 rapid antigen detection (RAD) tests and the factors that cause nonspecific reactions. METHODS: Nasopharyngeal swab specimens (n = 100), sputum specimens (n = 10), and lithium-heparin plasma samples (n = 100) were collected. We evaluated Espline®SARS-CoV-2 (Espline) and SARS-CoV-2 Rapid Antigen Test that also known as STANDARD Q® (STANDARD Q), with reverse transcription-polymerase chain reaction (RT-PCR) and Lumipulse® Presto SARS-CoV-2 Ag as reference tests. In addition, we investigated the effects of inadequate pretreatment methods and five potential causes of nonspecific reactions. RESULTS: The sensitivities of Espline and STANDARD Q were 60% and 57%, respectively, and their specificity was 100%. It was confirmed that the judgment line for the positive insufficiently mixed specimens was faint. A false-positive result was observed with STANDARD Q when sputum was used as a specimen to investigate judgment the effect of viscosity. CONCLUSIONS: Espline and STANDARD Q show good sensitivity for specimens with Ct values less than 25, but specimens collected within 9 days of symptom onset may still give false negatives. The test should be performed carefully, and the results should be judged comprehensively, taking into account clinical symptoms and patient background.

    DOI PubMed

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Misc 【 display / non-display 】

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Research Projects 【 display / non-display 】

  • Epidemiological and therapeutical study of pathogens associated to non-gonococcal urethritis

    Grant-in-Aid for Scientific Research (B)

    Project Year :

    2013.04
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    2016.03
     

    MATSUMOTO TETSURO, HAMASUNA Ryoichi, TAKAHASHI Satoshi, FUKUDA Kazumasa

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    From the specimens of male urethritis, many kinds of microorganisms are detected, but the pathogenicities of microorganisms except for N. gonorrhoeae or C. trachomatis has not been determined. As the new approach, the clone library method was used for analysis of microorganisms of urethritis. This method added quantitative concept to qualitative PCR methods. By this method, the pathogenicities of N. gonorrhoeae adn M. genitalium to the male urethra was confirmed. In addition, it was found that H. influenzae and N. meningitidis would be possible pathogens for male urethritis. By the examination of microorganisms in the oral cavities of patients with male urethritis, it was found that causative bacteria of male urethritis and bacteria of the resident flora in the vagina were detected in the oral cavities of male patients. these indicated that oral sex is closely related to STIs. When we treat male urethritis, we have to eradicate microorganisms in both the urethra and oral cavities.

  • Clinical study on the effect of androgen to organs other genitalis

    Grant-in-Aid for Scientific Research (C)

    Project Year :

    2007
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    2008
     

    KOBAYASHI Ko, MASUMORI Naoya, TAKAHASHI Satoshi

  • The relationship of the inflammatory infiltrating cell in prostate grand and chemokine

    Grant-in-Aid for Scientific Research (C)

    Project Year :

    2001
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    2003
     

    ITOH Naoki, TAKAHASHI Satoshi, MASUMORI Naoya, TSUKAMOTO Taiji, HOTTA Hiroshi

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    (1)The pathological study of inflammatory cell infiltration in the prostate in patients Patients entered into the study received radical cystoprostatectomy because of invasive bladder cancer in our institute from 1998 to 2000. The infiltrating cell type was assessed by immunostaining using a series of antibodies CD2O, CD45RO, CD68,S-100. The types of infiltrating cells were dominantly T cells. Inflammatory cell infiltration was seen in 32.4% cases. (2)Antimicrobial agents and suppression of cytokine secretion of prostate cancer cell line. PC-3,a human prostate cancer cell lines, was used for the experiment. IL-8 concentrations of the supematants were increased depending on the concentrations of Mycoplasma hominis. The mRNA of Toll like receptor-2 and Toll like receptor4 were demonstrated by RT-PCR in PC-3 cell lines. The activities of NF-κB were increased depending on the concentration of Mycoplasma hominisa. These data show that the signals from Toll-like receptor up the activities of NF-κB and lead to produce of IL-8. The influence of GFLX on IL-8 mRNA expression was analyzed using RT-PCR. GFLX significantly attenuated the TNF-α induced IL-8 mRNA level. GFLX suppresses the secretion of IL-8 from PC-3 in a dose-dependent manner. The results may imply that GFLX has an anti-inflammatory effect on chronic prostatitis.

  • Study on the regulation mechanism of proliferation and differentiation of human prostatic stromal cells: Effects of TGF-βs on human prostatic myofibroblast and α-adrenergic receptor.

    Grant-in-Aid for Scientific Research (C)

    Project Year :

    1999
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    2001
     

    TAKAHASHI Satoshi, TAKAHASHI Atsushi, MASUMORI Naoya, ITOH Naoki, KUNISHIMA Yasuharu, SASAMURA Hiroto

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    In order to study the effects of TGF-βs on human prostatic stromal cells, we purified human prostatic myofibroblast using specimens that was taken by operations and established culture system of these cells. These cells were immunohistochemically recognized as myofibroblast according to the findings of positive staining of a-smooth muscle actin and negative staining of both myosin and desmin. The expressions of TCF-β receptor I, II mRNA were confirmed by RT-PCR in these cells. After the treatment of various concentrations of human TGF-β1, 2, 3, it was recognized that these cells expressed both myosin and desmin. These findings suggested that TGF-βs could differentiate myofibroblast to smooth muscle. On the other hand, TGF-β1, 2, 3 inhibited proliferation of myofibroblast by dose-dependent manner. It has been well known that there are three subtypes of α1-receptor in human prostatic tissue; 1a, 1b and 1d, however the distribution of these subtypes in myofibroblast and smooth muscle cells has not been clarified. Using myofibroblast that was established by us and human prostatic smooth muscle that was commercially available, the expressions of 1a, 1b, 1d subtype mRNA were quantitatively analyzed by real time RT-PCR. The expression of 1a was recognized in smooth muscle only, and both 1b and 1d were determined in myofibroblast and smooth muscle cells. Based on these findings, it was speculated that the expression of ala receptor mRNA was induced during the differentiation from myofibroblast to smooth muscle. To clarify the effect of TGF-β1 on the expression of α1 receptor in myofibroblast and smooth muscle, the expressios of α1a, 1b, 1d receptor mRNA were quantitatively analyzed by real time RT-PCR. Moreover, α1 receptor binding assay was performed using [^<125 >I] HEAT as a ligand. The expression of ala was detected in these cells cultured under the condition without TGF-β1. The expressions of 1b and 1d without TGF-β were significantly higher 0.13 and 0.09 times respectively than with TGF-β1. Bmax of [^^<125>I]HEAT (300pM) was 37.5 fmol/mg protein in the medium without TGF-β1 and 21.3fmol/mg protein in those with TGF-β1. It was concluded that TGF-βs could have human prostatic myofibroblast differentiate to smooth muscle cell. On the other hand, the function of smooth muscle was undifferentiated by TGF-β1, because the expression of al receptor was suppressed by it. Based on these results, it was speculated that the regulatory mechanisms of morphological differentiation might be different from these of functional differentiation in human prostatic stroma.

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