Faculty Profiles - SHIBAYAMA Keigo

Papers - SHIBAYAMA Keigo

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鈴木仁人, 林原絵美子, 松井英則, 徳永健吾, 柴山恵吾

日本ヘリコバクター学会誌 Vol. 24 ( 1 ) page： 2 - 9 2022.5

Language：Japanese Publisher：(一社)日本ヘリコバクター学会

Helicobacter suisはブタが自然宿主と考えられている細菌で、ヒト胃での持続感染は胃粘膜関連リンパ組織(MALT)リンパ腫などの胃関連疾患の発症に関連していることが指摘されている。H.suisは過去にブタから単離培養されていたが、ヒトからの分離はなされていなかったため、ヒトにおいてH.suis感染と胃関連疾患発症の因果関係の証明は不完全なままとなっていた。本研究では、われわれはヒト胃から直接的にH.suisを分離し、in vitroで培養することに成功した。H.suisはHelicobacter pyloriと異なり、中性pHで著しく生存率が低下するため、胃生検の輸送には低pH培地を用いた。最終的に胃MALTリンパ腫を含む胃関連疾患患者3名からH.suisを分離することができた。患者全員において抗菌治療によりH.suisの除菌に成功し、内視鏡所見、病理組織学的所見が有意に改善された。H.suis臨床分離株をマウスに経口感染させると、胃粘膜で持続感染し、胃局所および全身性の炎症反応が惹起され、感染4ヵ月後には胃粘膜上皮化生が進行することが確認された。また、感染マウスの胃からH.suisが分離されたことから、本菌はヒトの胃関連疾患の起因菌としてコッホの原則を満たす形で初めて証明された。臨床分離株を用いたH.suisの比較ゲノム解析により、各分離株の染色体にはIV型分泌機構関連遺伝子などの株特異的な病原因子をコードする可塑性の高い領域が存在していること、ヒトとブタの分離株は遺伝的に非常に似ており、ブタ-ヒト感染の可能性があることが示唆された。(著者抄録)

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Establishment of a reference panel of Helicobacter pylori strains for antimicrobial susceptibility testing. International journal Open Access

Kenji Yokota, Takako Osaki, Shunji Hayashi, Shin-Ichi Yokota, Hiroaki Takeuchi, Emiko Rimbara, Hinako Ojima, Toyotaka Sato, Hideo Yonezawa, Keigo Shibayama, Kengo Tokunaga, Shigeru Kamiya, Kazunari Murakami, Mototsugu Kato, Toshiro Sugiyama

Helicobacter Vol. 27 ( 3 ) page： e12874 2022.3

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Eradication treatment for Helicobacter pylori gastritis is covered by national health insurance since 2013 in Japan. However, eradication failure due to the increase of antimicrobial resistance has become a serious problem. The present study aims to establish a reference panel of Japanese H. pylori strains for antimicrobial susceptibility testing. METHOD: A total of 28 strains were collected from 4 medical facilities in Japan. Antimicrobial susceptibility tests (ASTs) to clarithromycin (CLR), amoxicillin (AMX), and metronidazole (MNZ), were used to select standard reference strains. Complete genome sequences were also determined. RESULTS: Three H. pylori strains (JSHR3, JSHR6 and JSHR31) were selected as standard reference strains by the Japanese Society for Helicobacter Research (JSHR). The minimum inhibitory concentrations (MICs) of the antibiotics against these 3 strains by agar dilution method with Brucella-based horse-serum-containing agar medium were as follows: JSHR3 (CLR 16 μg/ml, AMX 0.032 μg/ml and MNZ 4 μg/ml), JSHR6 (CLR 0.016 μg/ml, AMX 0.032 μg/ml and MNZ 4 μg/ml), and JSHR31 (CLR 16 μg/ml, AMX 1 μg/ml and MNZ 64 μg/ml). CONCLUSIONS: A reference panel of H. pylori JSHR strains was established. The panel consisted of JSHR6, which was antibiotic-susceptible, JSHR3, which was CLR-resistant, and JSHR31, which was multi-resistant. This reference panel will be essential for standardized ASTs before the optimal drugs are selected for eradication treatment.

DOI： 10.1111/hel.12874

The First Reported Case of Bordetella pertussis Bacteremia in a Patient With Human Immunodeficiency Virus Infection. International journal Open Access

Yuji Wakimoto, Nao Otsuka, Yasuaki Yanagawa, Kentaro Koide, Kazunari Kamachi, Keigo Shibayama, Katsuji Teruya, Yoshimi Kikuchi, Shinichi Oka

Open forum infectious diseases Vol. 9 ( 3 ) page： ofac020 2022.3

Language：English

We describe a case of bacteremia in a human immunodeficiency virus-infected patient caused by a Bordetella pertussis strain lacking 2 major virulence factors, filamentous hemagglutinin and fimbriae. Although B pertussis bacteremia is uncommon, physicians should be aware that even attenuated B pertussis strains can cause invasive infection in immunocompromised patients. Bordetella pertussis is a gram-negative coccobacillus that causes a severe paroxysmal coughing disease known as whooping cough or pertussis. Bordetella pertussis colonizes the epithelial cells of the human respiratory tract, and the organisms are typically isolated from nasopharynx. We describe a case of B pertussis bacteremia in a patient with human immunodeficiency virus (HIV) infection. Interestingly, the isolate recovered from blood culture did not produce the major virulence factors, filamentous hemagglutinin (FHA) and fimbriae (FIM). Previously, 3 cases of B pertussis bacteremia were reported in the literature. We discuss the features of B pertussis bacteremia.

DOI： 10.1093/ofid/ofac020

Emergence of mobile tigecycline resistance gene tet(X4)–harboring Shewanella xiamenensis in a water environment Reviewed International journal

Trung Duc Dao, Ikuro Kasuga, Aki Hirabayashi, Dong Tu Nguyen, Hien Thi Tran, Hieu Vu, Linh Tuyet Ngoc Pham, Thi My Hanh Vu, Futoshi Hasebe, Ha Thanh Nguyen, Trang Le Thi, Hoang Huy Tran, Keigo Shibayama, Taichiro Takemura, Masato Suzuki

Journal of Global Antimicrobial Resistance Vol. 28 page： 140 - 142 2022.3

Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier BV

OBJECTIVES: Tigecycline resistance mediated by the mobile tigecycline-inactivating enzyme gene tet(X) in Gram-negative bacteria is an emerging concern for global public health. However, limited information is available on the distribution of tet(X) in the natural environment. In this study, we investigated the presence of tet(X) in environmental Gram-negative bacteria. METHODS: A carbapenem- and tigecycline-resistant Shewanella xiamenensis isolate (NUITM-VS1) was obtained from an urban drainage in Hanoi, Vietnam, in March 2021. Whole-genome sequencing analysis was performed by long- and short-read sequencing, resulting in a complete genome sequence. Antimicrobial resistance genes (ARGs) in the genome were detected based on the custom ARG database, including all known tigecycline resistance genes. RESULTS: Shewanella xiamenensis isolate NUITM-VS1 harboured the tet(X4) gene and the blaOXA-48 carbapenemase gene on the chromosome. tet(X4) was flanked by IS91 family transposase genes, suggesting that the acquisition of tet(X4) was mediated by this mobile gene element (MGE), whereas no MGE was found surrounding blaOXA-48, consistent with previous findings that blaOXA-48-like β-lactamase genes are species-specific intrinsic ARGs in Shewanella spp. CONCLUSION: To the best of our knowledge, this is the first report of a tet(X4)-harbouring Shewanella sp. isolate. Our results provide genetic evidence of the complexity of the dynamics of clinically important ARGs among bacteria in the water environment.

DOI： 10.1016/j.jgar.2021.12.022

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H.pyloriと胃がん以外の疾患ここまで解明された Helicobacter suisを中心に

徳永健吾, 林原絵美子, 鈴木仁人, 柴山恵吾, 松井英則

日本胃癌学会総会記事 Vol. 94回 page： 528 - 528 2022.3

H.pyloriと胃がん以外の疾患ここまで解明された Helicobacter suisを中心に

徳永健吾, 林原絵美子, 鈴木仁人, 柴山恵吾, 松井英則

日本胃癌学会総会記事 Vol. 94回 page： 528 - 528 2022.3

Genomic characterization of triple-carbapenemase-producing Acinetobacter baumannii Reviewed International journal Open Access

Ken-Ichi Oinuma, Masato Suzuki, Arata Sakiyama, Taishi Tsubouchi, Kozo Saeki, Kanako Sato, Mamiko Niki, Koichi Yamada, Keigo Shibayama, Hiroshi Kakeya, Yukihiro Kaneko

JAC-Antimicrobial Resistance Vol. 3 ( 4 ) page： dlab191 2021.12

Language：English Publishing type：Research paper (scientific journal) Publisher：Oxford University Press (OUP)

<title>Abstract</title>
<sec>
<title>Objectives</title>
To characterize Acinetobacter baumannii OCU_Ac16a, a clinical isolate co-harbouring three acquired carbapenemase genes, blaNDM-1, blaTMB-1, and blaOXA-58, and assess the clinical significance of so-called multiple-carbapenemase producers.

</sec>
<sec>
<title>Methods</title>
OCU_Ac16a and its close relative, OCU_Ac16b, which lacks the blaNDM-1, were isolated from sputum cultures of a patient at Osaka City University Hospital. We subjected these strains to whole-genome analysis, particularly focusing on the genetic context of each carbapenemase gene. The transmissibility and functionality of each carbapenemase gene were analysed by conjugation and transformation experiments and antimicrobial susceptibility tests.

</sec>
<sec>
<title>Results</title>
bla TMB-1 was located in a class 1 integron on the chromosome, whereas blaNDM-1 and blaOXA-58 were found on plasmids named pOCU_Ac16a_2 and pOCU_Ac16a_3, respectively. pOCU_Ac16a_2 (which exhibited highly efficient self-transmissibility) and pOCU_Ac16a_3 (which did not show transmissibility but could be introduced into another A. baumannii strain via electroporation) could both confer carbapenem resistance (MICs ≥512 and ≥32 mg/L, respectively) on the recipient strain. The functionality of blaTMB-1 was evident from the high resistance of OCU_Ac16b to ceftazidime and cefepime (MICs ≥256 and 48 mg/L, respectively), and the high resistance of OCU_Ac16a to cefiderocol (MIC 32 mg/L) could be explained by the additive effect of blaNDM-1 and blaTMB-1.

</sec>
<sec>
<title>Conclusions</title>
Our data revealed the genomic organization of OCU_Ac16a and demonstrated that all the carbapenemase genes are functional, each contributing to the extremely high broad-spectrum resistance of OCU_Ac16a to β-lactams. As multiple-carbapenemase producers can be serious health threats as drug-resistant pathogens and disseminators of carbapenemase genes, close attention should be paid to their emergence.

</sec>

DOI： 10.1093/jacamr/dlab191

Potential spread of mcr-9-carrying IncHI2 plasmids in Enterobacter hormaechei in Vietnam. Reviewed International journal

Van Thi Thu Ha, Linh Dieu Tran, Nguyen Thi Tuyet Mai, Aki Hirabayashi, Son Thai Nguyen, Hoang Huy Tran, Keigo Shibayama, Masato Suzuki

Journal of global antimicrobial resistance Vol. 27 page： 332 - 334 2021.11

Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: Mobile colistin resistance (mcr) genes are widely distributed around the world. To date, ten major variants of mcr genes are known (mcr-1 to mcr-10). However, only a few instances of Enterobacterales isolates harbouring mcr genes other than mcr-1 have been reported in Vietnam. The aim of this study was to investigate mcr-harbouring antimicrobial-resistant Enterobacterales isolates in Vietnam. METHODS: Two mcr-9-harbouring Enterobacter hormaechei clinical isolates (NIHE14-1904 and MH17-539M) were obtained from medical institutions in Hanoi, Vietnam, in 2014 and 2017, respectively. Their genomes and plasmid sequences were analysed by short-read and long-read sequencing. Subsequently, comparative sequence analysis of their mcr-9-carrying plasmids was performed. RESULTS: Strains NIHE14-1904 and MH17-539M belonged to sequence types ST916 and ST66, respectively, according to the Enterobacter cloacae multilocus sequence typing (MLST) scheme. NIHE14-1904 and MH17-539M harboured the mcr-9 gene on similar IncHI2 plasmids, namely pNIHE14-1904-mcr9 (373.1 kb) and pMH17-539M-mcr9 (289.3 kb), respectively. These plasmids were also highly identical to widespread IncHI2 plasmids that are often associated with mcr genes. CONCLUSION: For the first time, mcr-9-harbouring Enterobacterales isolates were detected in Vietnam, which carried mcr-9 on IncHI2 plasmids. The prevalence of such plasmids needs to be monitored in the future owing to their high dissemination.

DOI： 10.1016/j.jgar.2021.09.012

Expansion of KPC–producing Enterobacterales in four large hospitals in Hanoi, Vietnam Reviewed International journal

Tran Dieu Linh, Nguyen Hoai Thu, Keigo Shibayama, Masato Suzuki, LayMint Yoshida, Pham Duy Thai, Dang Duc Anh, Tran Nhu Duong, Hong Son Trinh, Vu Phuong Thom, Luu Thi Vu Nga, Nguyen Thi Kim Phuong, Bui Thanh Thuyet, Timothy R Walsh, Le Viet Thanh, Anne-Laure Bañuls, H Rogier van Doorn, Tran Van Anh, Tran Huy Hoang

Journal of Global Antimicrobial Resistance Vol. 27 page： 200 - 211 2021.10

Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier BV

OBJECTIVES: The incidence of carbapenem resistance among nosocomial Gram-negative bacteria in Vietnam is high and increasing, including among Enterobacterales. In this study, we assessed the presence of one of the main carbapenemase genes, blaKPC, among carbapenem-resistant Enterobacterales (CRE) from four large hospitals in Hanoi, Vietnam, between 2010 and 2015, and described their key molecular characteristics. METHODS: KPC-producing Enterobacterales were detected using conventional PCR and were further analysed using S1 nuclease pulsed-field gel electrophoresis (S1-PFGE), Southern blotting and whole-genome sequencing (WGS) for sequence typing and genetic characterisation. RESULTS: blaKPC genes were detected in 122 (20.4%) of 599 CRE isolates. blaKPC-carrying plasmids were diverse in size. Klebsiella pneumoniae harbouring blaKPC genes belonged to ST15 and ST11, whereas KPC-producing Escherichia coli showed more diverse sequence types including ST3580, ST448, ST709 and ST405. Genotypic relationships supported the hypothesis of circulation of a population of 'resident' resistant bacteria in one hospital through the years and of transmission among these hospitals via patient transfer. WGS results revealed co-carriage of several other antimicrobial resistance genes and three different genetic contexts of blaKPC-2. Among these, the combination of ISEcp1-blaCTX-M and ISKpn27-blaKPC-ΔISKpn6 on the same plasmid is reported for the first time. CONCLUSION: We describe the dissemination of blaKPC-expressing Enterobacterales in four large hospitals in Hanoi, Vietnam, since 2010, which may have started earlier, along with their resistance patterns, sequence types, genotypic relationship, plasmid sizes and genetic context, thereby contributing to the overall picture of the antimicrobial resistance situation in Enterobacterales in Vietnam.

DOI： 10.1016/j.jgar.2021.09.007

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Impact of the COVID-19 pandemic on the surveillance of antimicrobial resistance. Reviewed International journal

Aki Hirabayashi, Toshiki Kajihara, Koji Yahara, Keigo Shibayama, Motoyuki Sugai

The Journal of hospital infection Vol. 117 page： 147 - 156 2021.9

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The impact of the coronavirus disease (COVID-19) pandemic on antimicrobial resistance (AMR) is a major concern. AIM: To compare the number of patients and isolation rate of antimicrobial-resistant bacteria before and after the beginning of the COVID-19 pandemic using the comprehensive national surveillance data. METHODS: We utilized comprehensive surveillance data, collected in the Japan Nosocomial Infections Surveillance program, which included a total of 16.7 million samples of 5.9 million tested patients from >1,300 hospitals. We compared the number of patients and isolation rate of five bacteria between 2019 and 2020, including antimicrobial-susceptible and -resistant bacteria of Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. FINDINGS: The number of patients and isolation rate of S. aureus and methicillin-resistant S. aureus decreased slightly; those of S. pneumoniae and penicillin-resistant S. pneumoniae decreased by 60%; and those of third-generation cephalosporin-resistant K. pneumoniae increased. The isolation rate of the remaining bacteria apparently increased, although the number of patients decreased. This was due to a substantial decrease in the total number of tested patients (the denominator of the isolation rate), which was larger than that of the number of patients (the numerator of the isolation rate). Consistent results were obtained when the same data were re-aggregated using the procedure of the World Health Organization Global Antimicrobial Resistance Surveillance System, demonstrating the general importance of this problem. CONCLUSION: Surveillance data during the COVID-19 pandemic must be carefully interpreted based on examination of the numerator, denominator and background factors that affect the denominator.

DOI： 10.1016/j.jhin.2021.09.011

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Resistance mechanisms and genetic relatedness among carbapenem-resistant Pseudomonas aeruginosa isolates from three major hospitals in Hanoi, Vietnam (2011-15). International journal Open Access

Hai Anh Tran, Thi Ngoc Bich Vu, Son Tung Trinh, Dieu Linh Tran, Ha My Pham, Thi Hong Hanh Ngo, Minh Thao Nguyen, Nhu Duong Tran, Duy Thai Pham, Duc Anh Dang, Keigo Shibayama, Masato Suzuki, Lay-Myint Yoshida, Hong Son Trinh, Viet Thanh Le, Phuong Thom Vu, Thi Vu Nga Luu, Anne-Laure Bañuls, Khanh Linh Trinh, Van Anh Tran, Huy Hoang Tran, H Rogier van Doorn

JAC-antimicrobial resistance Vol. 3 ( 3 ) page： dlab103 2021.9

Language：English Publishing type：Research paper (scientific journal)

Background: MDR bacteria including carbapenem-resistant Pseudomonas aeruginosa are recognized as an important cause of hospital-acquired infections worldwide. This investigation seeks to determine the molecular characterization and antibiotic resistance genes associated with carbapenem-resistant P. aeruginosa. Methods: We conducted WGS and phylogenetic analysis of 72 carbapenem-resistant P. aeruginosa isolated from hospital-acquired infection patients from August 2011 to March 2015 in three major hospitals in Hanoi, Vietnam. Results: We identified three variants of IMP gene, among which bla IMP-15 was the most frequent (n = 34) in comparison to bla IMP-26 (n = 2) and bla IMP-51 (n = 12). We observed two isolates with imipenem MIC >128 mg/L that co-harboured bla IMP-15 and bla DIM-1 genes and seven isolates (imipenem MIC > 128 mg/L) with a bla KPC-1 gene from the same hospital. MLST data shows that these 72 isolates belong to 18 STs and phylogenetic tree analysis has divided these isolates into nine groups. Conclusions: Our results provide evidence that not only bla IMP-26 but other IMP variants such as bla IMP-15 and bla IMP-51 genes and several STs (ST235, ST244, ST277, ST310, ST773 and ST3151) have been disseminating in healthcare settings in Vietnam. In addition, we report the emergence of two isolates belonging to ST1240 and ST3340 that harboured two important carbapenemase genes (bla IMP-15 and bla DIM-1) and seven isolates belonging to ST3151 of P. aeruginosa that carried the bla KPC-1 gene in Vietnam, which could potentially cause serious restricted availability of treatment options in healthcare settings.

DOI： 10.1093/jacamr/dlab103

Helicobacter suis胃粘膜感染と病態発症

鈴木仁人, 林原絵美子, 松井英則, 徳永健吾, 柴山恵吾

日本ヘリコバクター学会学術集会プログラム・抄録集 Vol. 27回 page： 147 - 147 2021.9

イヌおよびネコの胃生検組織から分離された2つの新種Helicobacter属菌

青木沙恵, 鈴木仁人, 森茂太郎, 柴山恵吾, 大野耕一, 見理剛, 林原絵美子

日本ヘリコバクター学会学術集会プログラム・抄録集 Vol. 27回 page： 196 - 196 2021.9

アシネトバクター属菌に拡散しているcGAS遺伝子陽性プラスミド

鈴木仁人, 浅井さとみ, 平林亜希, 氣駕恒太朗, 相羽由詞, 渡邊真弥, 梅澤和夫, 宮地勇人, 崔龍洙, 柴山恵吾

緑膿菌感染症研究会講演記録 Vol. 55回 page： 20 - 20 2021.9

Helicobacter基礎研究の最前線 Helicobacter suisなどのNon-Helicobacter pylori Helicobacterの細菌学的特徴およびゲノム比較

林原絵美子, 鈴木仁人, 徳永健吾, 間部克裕, 南條宗八, 松井英則, 青木沙恵, 森茂太郎, 大野耕一, 柴山恵吾, 見理剛

日本ヘリコバクター学会学術集会プログラム・抄録集 Vol. 27回 page： 173 - 173 2021.9

A Transferable IncC-IncX3 Hybrid Plasmid Cocarrying blaNDM-4, tet(X), and tmexCD3-toprJ3 Confers Resistance to Carbapenem and Tigecycline. International journal Open Access

Aki Hirabayashi, Trung Duc Dao, Taichiro Takemura, Futoshi Hasebe, Le Thi Trang, Nguyen Ha Thanh, Hoang Huy Tran, Keigo Shibayama, Ikuro Kasuga, Masato Suzuki

mSphere Vol. 6 ( 4 ) page： e0059221 - 6 2021.8

Language：English Publishing type：Research paper (scientific journal)

Tigecycline is a last-resort antimicrobial against carbapenemase-producing Enterobacterales (CPE). However, mobile tigecycline resistance genes, tet(X) and tmexCD-toprJ, have emerged in China and have spread possibly worldwide. Tet(X) family proteins function as tigecycline-inactivating enzymes, and TMexCD-TOprJ complexes function as efflux pumps for tigecycline. Here, to the best of our knowledge we report a CPE isolate harboring both emerging tigecycline resistance factors for the first time. A carbapenem- and tigecycline-resistant Klebsiella aerogenes strain, NUITM-VK5, was isolated from an urban drainage in Vietnam in 2021, and a plasmid, pNUITM-VK5_mdr, cocarrying tet(X) and tmexCD3-toprJ3 along with the carbapenemase gene blaNDM-4 was identified in NUITM-VK5. pNUITM-VK5_mdr was transferred to Escherichia coli by conjugation and simultaneously conferred high-level resistance against multiple antimicrobials, including carbapenems and tigecycline. An efflux pump inhibitor reduced TMexCD3-TOprJ3-mediated tigecycline resistance, suggesting that both tigecycline resistance factors independently and additively contribute to the high-level resistance. The plasmid had the IncX3 and IncC replicons and was estimated to be a hybrid of plasmids with different backbones. Unlike IncX3 plasmids, IncC plasmids are stably maintained in an extremely broad range of bacterial hosts in humans, animals, and the environment. Thus, the future global spread of multidrug resistance plasmids such as pNUITM-VK5_mdr poses a public health crisis. IMPORTANCE Tigecycline is important as a last-resort antimicrobial and effective against antimicrobial-resistant bacteria, such as carbapenem-producing Enterobacterales (CPE), whose infections are difficult to treat with antimicrobials. Since 2019, mobile tigecycline resistance genes, tet(X) and tmexCD-toprJ, and their variants have been reported mainly from China, and it has become important to understand their epidemiological situation and detailed genetic mechanisms. In this study, we identified a bacterial isolate coharboring tet(X) and tmexCD-toprJ on the same plasmid. A Klebsiella aerogenes isolate in Vietnam carried both these tigecycline resistance genes on a transferable plasmid leading to high-level resistance to multiple clinically important antimicrobials, including carbapenem and tigecycline, and could actually transfer the plasmid to other bacteria. The spread of such a multidrug resistance plasmid among bacterial pathogens should be of great concern because there are few antimicrobials to combat bacteria that have acquired the plasmid.

DOI： 10.1128/mSphere.00592-21

Disease burden of bloodstream infections caused by antimicrobial-resistant bacteria: A population-level study, Japan, 2015-2018. Reviewed International journal

Shinya Tsuzuki, Nobuaki Matsunaga, Koji Yahara, Keigo Shibayama, Motoyuki Sugai, Norio Ohmagari

International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases Vol. 108 page： 119 - 124 2021.7

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Antimicrobial resistance (AMR) is a global health problem. However, quantitative evaluation of its disease burden is challenging. This study aimed to estimate the disease burden of bloodstream infections (BSIs) caused by major antimicrobial-resistant bacteria in Japan between 2015 and 2018 in terms of disability-adjusted life-years (DALYs). METHODS: DALYs of BSIs caused by nine major antimicrobial-resistant bacteria in Japan were estimated using comprehensive national surveillance data of all routine bacteriological test results from more than 1400 hospitals between 2015 and 2018. The methodology of Cassini et al. was modified to enable comparison of the present results with those in other countries. RESULTS: It was estimated that 137.9 [95% uncertainty interval (UI) 130.7-145.2] DALYs per 100,000 population were attributable to BSIs caused by nine antimicrobial-resistant bacteria in 2018. Methicillin-resistant Staphylococcus aureus (MRSA), fluoroquinolone-resistant Escherichia coli (FQREC) and third-generation cephalosporin-resistant E. coli (3GREC) accounted for 87.2% overall. The burden did not decrease during the study period and was highest in people aged ≥65 years. CONCLUSION: The results revealed, for the first time, the disease burden of BSIs caused by nine major antimicrobial-resistant bacteria in Japan. The estimated disease burden associated with AMR in Japan is substantial and has not begun to decrease. Notably, the burden from FQREC and 3GREC has increased steadily, and that from MRSA is larger in Japan than in the European Union/European Economic Area, whereas the burden from other bacteria is comparatively small. These results are expected to provide useful information for healthcare policy makers for prioritizing interventions for AMR.

DOI： 10.1016/j.ijid.2021.05.018

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Molecular ruler of the attachment organelle in Mycoplasma pneumoniae. Reviewed International journal

Daisuke Nakane, Kohki Murata, Tsuyoshi Kenri, Keigo Shibayama, Takayuki Nishizaka

PLoS pathogens Vol. 17 ( 6 ) page： e1009621 2021.6

Language：English Publishing type：Research paper (scientific journal)

Length control is a fundamental requirement for molecular architecture. Even small wall-less bacteria have specially developed macro-molecular structures to support their survival. Mycoplasma pneumoniae, a human pathogen, forms a polar extension called an attachment organelle, which mediates cell division, cytadherence, and cell movement at host cell surface. This characteristic ultrastructure has a constant size of 250-300 nm, but its design principle remains unclear. In this study, we constructed several mutants by genetic manipulation to increase or decrease coiled-coil regions of HMW2, a major component protein of 200 kDa aligned in parallel along the cell axis. HMW2-engineered mutants produced both long and short attachment organelles, which we quantified by transmission electron microscopy and fluorescent microscopy with nano-meter precision. This simple design of HMW2 acting as a molecular ruler for the attachment organelle should provide an insight into bacterial cellular organization and its function for their parasitic lifestyles.

DOI： 10.1371/journal.ppat.1009621

Induction and Resuscitation of Viable but Nonculturable Corynebacterium diphtheriae. Reviewed International journal

Takashi Hamabata, Mitsutoshi Senoh, Masaaki Iwaki, Ayae Nishiyama, Akihiko Yamamoto, Keigo Shibayama

Microorganisms Vol. 9 ( 5 ) 2021.4

Language：English Publishing type：Research paper (scientific journal)

Many pathogenic bacteria, including Escherichia coli and Vibrio cholerae, can become viable but nonculturable (VBNC) following exposure to specific stress conditions. Corynebacterium diphtheriae, a known human pathogen causing diphtheria, has not previously been shown to enter the VBNC state. Here, we report that C. diphtheriae can become VBNC when exposed to low temperatures. Morphological differences in culturable and VBNC C. diphtheriae were examined using scanning electron microscopy. Culturable cells presented with a typical rod-shape, whereas VBNC cells showed a distorted shape with an expanded center. Cells could be transitioned from VBNC to culturable following treatment with catalase. This was further evaluated via RNA sequence-based transcriptomic analysis and reverse-transcription quantitative PCR of culturable, VBNC, and resuscitated VBNC cells following catalase treatment. As expected, many genes showed different behavior by resuscitation. The expression of both the diphtheria toxin and the repressor of diphtheria toxin genes remained largely unchanged under all four conditions (culturable, VBNC, VBNC after the addition of catalase, and resuscitated cells). This is the first study to demonstrate that C. diphtheriae can enter a VBNC state and that it can be rescued from this state via the addition of catalase. This study helps to expand our general understanding of VBNC, the pathogenicity of VBNC C. diphtheriae, and its environmental survival strategy.

DOI： 10.3390/microorganisms9050927

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Association between the frequency of surgeries for video-assisted thoracic surgery and the incidence of consequent surgical site infections: a retrospective observational study based on national surveillance data. Reviewed International journal

Toshiki Kajihara, Koji Yahara, Aki Hirabayashi, Hitomi Kurosu, Motoyuki Sugai, Keigo Shibayama

BMC infectious diseases Vol. 21 ( 1 ) page： 363 - 363 2021.4

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: The association between the frequency of surgeries and the incidence of surgical site infections (SSIs) has been reported for various surgeries. However, no previous study has explored this association among video-assisted thoracic surgeries (VATS). Hence, we aimed to investigate the association between the frequency of surgeries and SSI in video-assisted thoracic surgeries. METHODS: We analyzed the data of 26,878 thoracic surgeries, including 21,154 VATS, which were collected during a national surveillance in Japan between 2014 and 2018. The frequency of surgeries per hospital department was categorized into low (< 50/year), moderate (50-100/ year), and high (> 100/year). Chi-squared test or Fisher's exact test was used for discrete explanatory variables, whereas Wilcoxon's rank-sum test or Kruskal-Wallis test was used for continuous explanatory variables. Univariate analysis of the department groups was conducted to explore confounding factors associated with both SSIs and the department groups. We used a multiple logistic regression model focusing on VATS and stratified by the National Nosocomial Infections Surveillance System (NNIS) risk index. RESULTS: The rates of SSIs in the hospital groups with low, moderate, and high frequency of surgeries were 1.39, 1.05, and 1.28%, respectively. In the NNIS risk index 1 stratum, the incidence of SSIs was significantly lower in the moderate-frequency of surgeries group than that in the other groups (odds ratio [OR]: vs. low-frequency of surgeries: 2.48 [95% confidence interval [CI]: 1.20-5.13], P = 0.0143; vs. high-frequency of surgeries: 2.43 [95% CI: 1.44-4.11], P = 0.0009). In the stratum of NNIS risk indices 2 and 3, the incidence of SSI was significantly higher in the low-frequency of surgeries group (OR: 4.83, 95% CI: 1.47-15.93; P = 0.0095). CONCLUSION: The result suggests that for departments with low-frequency of surgeries, an increase in the frequency of surgeries to > 50 per department annually potentially leads to a decrease in the incidence of SSIs. This occurs through an increase in the experience of the departmental surgeons and contributes to the improvement of VATS outcomes in thoracic surgeries.

DOI： 10.1186/s12879-021-06050-6

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