The association of gene mutation with clinical characyter in MRSA infection

• Project/Area Number: 18K08426
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54030:Infectious disease medicine-related
• Research Institution: Kanazawa University
• Principal Investigator: Iwata Yasunori 金沢大学, 附属病院, 特任教授 (90432137)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: MRSA / 遺伝子 / D-アミノ酸 / メチシリン耐性黄色ブドウ球菌 / バイオイルム / 遺伝子情報 / 感染症学 / 腎臓病学 / 腎臓内科学

Outline of Final Research Achievements

Methicillin-resistant Staphylococcus aureus (MRSA) is a common pathogenic bacterium that causes nosocomial and community-acquired infections. MRSA infection can cause severe illness not only in immunocompromised patients but also in healthy people. Therefore, the understanding the pathogenesis and developing novel therapeutic option are of important. We have focused on the association between bacterial gene and clinical phenotype on MRSA infection. We revealed that the bacterial genotype affects the clinical characteristics of MRSA infection. Moreover, The frequency of gene mutations on resistant gene loci were gradually decreased along with the increased sensitivity of beta-lactam antibiotics. Then, we found that D-Serine inhibits the attachment and biofilm formation of MRSA by reducing the expression of the related genes. These results highlight the association of gene mutation with phenotype of infection.

Academic Significance and Societal Importance of the Research Achievements

これらの結果は、菌体側の接着・バイオフィルム関連遺伝子情報が、感染症の病態と相関し、血流感染症の予知因子となる可能性を示していた。さらに、接着・バイオフィルム関連遺伝子が新規治療標的となる可能性も考えられ、新たなバイオマーカーや、新規抗菌薬開発のターゲットとして、有用であることが示された。今後の感染症対策を考えるうえで、重要な結果であると考えられた。

Research Products

• [Journal Article] D-Serine inhibits the attachment and biofilm formation of methicillin-resistant Staphylococcus aureus (2021)
  • Author(s): Iwata Y, Sakai N, Yoneda I, Senda Y, Sakai-Takemori Y, Oshima M, Nakagawa-Yoneda S, Ogura H, Sato K, Minami T, Kitajima S, Toyama T, Yamamura Y, Miyagawa T, Hara A, Shimizu M, Furuichi K, Matsushima K, Wada T.
  • Journal Title: Biochem Biophys Res Commun. Volume: 22 Pages: 50-56
  • DOI: 10.1016/j.bbrc.2020.12.078
  • Peer Reviewed / Open Access
• [Journal Article] Significance of the Gut Microbiota in Acute Kidney Injury (2021)
  • Author(s): Kobayashi Taku、Iwata Yasunori、Nakade Yusuke、Wada Takashi
  • Journal Title: Toxins Volume: 13 Issue: 6 Pages: 369-369
  • DOI: 10.3390/toxins13060369
  • Peer Reviewed / Open Access
• [Journal Article] Correction to: Renal complications in coronavirus disease 2019: a systematic review (2021)
  • Author(s): Minami Taichiro、Iwata Yasunori、Wada Takashi
  • Journal Title: Inflammation and Regeneration Volume: 41 Issue: 1
  • DOI: 10.1186/s41232-021-00171-w
• [Journal Article] Relationships between kidney dysfunction and left ventricular diastolic dysfunction: a hospital-based retrospective study (2021)
  • Author(s): Miyajima Yoshiyasu、Toyama Tadashi、Mori Mika、Nakade Yusuke、Sato Koichi、Yamamura Yuta、Ogura Hisayuki、Yoneda-Nakagawa Shiori、Oshima Megumi、Miyagawa Taro、Usui Soichiro、Oe Hiroyasu、Kitajima Shinji、Hara Akinori、Iwata Yasunori、Sakai Norihiko、Shimizu Miho、Sakai Yoshio、Furuichi Kengo、Wada Takashi
  • Journal Title: Journal of Nephrology Volume: 34 Issue: 3 Pages: 773-780
  • DOI: 10.1007/s40620-020-00940-9
• [Journal Article] Combined changes in albuminuria and kidney function and subsequent risk for kidney failure in type 2 diabetes (2021)
  • Author(s): Oshima Megumi、ToyaIwata Yasunori、et. al
  • Journal Title: BMJ Open Diabetes Research & Care Volume: 9 Issue: 1 Pages: e002311-e002311
  • DOI: 10.1136/bmjdrc-2021-002311
  • Peer Reviewed / Open Access
• [Journal Article] Carnitine/organic cation transporter 1 precipitates the progression of interstitial fibrosis through oxidative stress in diabetic nephropathy in mice (2021)
  • Author(s): Makiishi Shohei、Furuichi Kengo、Yamamura Yuta、Sako Keisuke、Shinozaki Yasuyuki、Toyama Tadashi、Kitajima Shinji、Iwata Yasunori、Sakai Norihiko、Shimizu Miho、Hirose-Sugiura Tomoko、Kaneko Shuichi、Kato Yukio、Wada Takashi
  • Journal Title: Scientific Reports Volume: 11 Issue: 1 Pages: 9093-9093
  • DOI: 10.1038/s41598-021-88724-4
  • Peer Reviewed / Open Access
• [Journal Article] Impact of the relationship between hemoglobin levels and renal interstitial fibrosis on long-term outcomes in type 2 diabetes with biopsy-proven diabetic nephropathy (2021)
  • Author(s): Shimizu Miho、Furuichi Kengo、Kitajima Shinji、Toyama Tadashi、Oshima Megumi、Ogura Hisayuki、Sato Koichi、Nakagawa Shiori、Yamamura Yuta、Miyagawa Taro、Hara Akinori、Iwata Yasunori、Sakai Norihiko、Kitagawa Kiyoki、Yoshimura Mitsuhiro、Yokoyama Hitoshi、Wada Takashi
  • Journal Title: BMC Nephrology Volume: 22 Issue: 1 Pages: 319-319
  • DOI: 10.1186/s12882-021-02510-y
  • Peer Reviewed / Open Access
• [Journal Article] Two-year longitudinal trajectory patterns of albuminuria and subsequent rates of end-stage kidney disease and all-cause death: a nationwide cohort study of biopsy-proven diabetic kidney disease (2021)
  • Author(s): Yamanouchi Masayuki、Iwata Yasunori、et al.
  • Journal Title: BMJ Open Diabetes Research & Care Volume: 9 Issue: 1 Pages: e002241-e002241
  • DOI: 10.1136/bmjdrc-2021-002241
  • Peer Reviewed / Open Access
• [Journal Article] The relationship between the modified National Institute of Health activity and chronicity scoring system, and the long-term prognosis for lupus nephritis: A retrospective single-center study (2021)
  • Author(s): Nakagawa Shiori、Toyama Tadashi、Iwata Yasunori、Oshima Megumi、Ogura Hisayuki、Sato Koichi、Yamamura Yuta、Miyakawa Taro、Kitajima Shinji、Hara Akinori、Sakai Norihiko、Shimizu Miho、Wada Takashi
  • Journal Title: Lupus Volume: 30 Issue: 11 Pages: 1739-1746
  • DOI: 10.1177/09612033211034234
• [Journal Article] Higher serum levels of autotaxin and phosphatidylserine-specific phospholipase A 1 in patients with lupus nephritis (2021)
  • Author(s): Iwata Y, Kitajima S, Yamahana J, Shimomura S, Yoneda-Nakagawa S, Sakai N, Furuichi K, Ogura H, Sato K, Toyama T, Yamamura Y, Miyagawa T, Hara A, Shimizu M, Ohkawa R, Kurano M, Yatomi Y, Wada T.
  • Journal Title: Int J Rheum Dis. Volume: 24 Issue: 2 Pages: 231-239
  • DOI: 10.1111/1756-185x.14031
  • Peer Reviewed / Open Access
• [Journal Article] Anti-proliferative and anti-migratory properties of coffee diterpenes kahweol acetate and cafestol in human renal cancer cells (2021)
  • Author(s): Makino T, Izumi K, Hiratsuka K, Kano H, Shimada T, Nakano T, Kadomoto S, Naito R, Iwamoto H, Yaegashi H, Shigehara K, Kadono Y, Nakata H, Saito Y, Nakagawa-Goto K, Sakai N, Iwata Y, Wada T, Mizokami A.
  • Journal Title: Sci Rep Volume: 11 Issue: 1 Pages: 675-675
  • DOI: 10.1038/s41598-020-80302-4
  • Peer Reviewed / Open Access
• [Journal Article] Renal complications in coronavirus disease 2019: a systematic review (2020)
  • Author(s): Minami T, Iwata Y, Wada T.
  • Journal Title: Inflamm Regen. Volume: 40 Issue: 1 Pages: 31-31
  • DOI: 10.1186/s41232-020-00140-9
  • Peer Reviewed
• [Journal Article] Age differences in the relationships between risk factors and loss of kidney function: a general population cohort study (2020)
  • Author(s): Toyama T, Kitagawa K, Oshima M, Kitajima S, Hara A, Iwata Y, Sakai N, Shimizu M, Hashiba A, Furuichi K, Wada T.
  • Journal Title: BMC Nephrol. Volume: 21 Issue: 1 Pages: 477-477
  • DOI: 10.1186/s12882-020-02121-z
  • Peer Reviewed / Open Access
• [Journal Article] Novel Hyaluronate Lyase Involved in Pathogenicity of Streptococcus dysgalactiae subsp. equisimilis (2020)
  • Author(s): Nguyen VA, Ogura K, Matsue M, Takemoto N, Mukai K, Nakajima Y, Hoang TL, Iwata Y, Sakai N, Wada T, Hashimoto W, Okamoto S, Ichimura H.
  • Journal Title: Front Microbiol Volume: 11 Pages: 552418-552418
  • DOI: 10.3389/fmicb.2020.552418
  • Peer Reviewed / Open Access
• [Journal Article] Collagen adhesion gene is associated with bloodstream infections caused by methicillin-resistant Staphylococcus aureus. (2020)
  • Author(s): Iwata Y, Satou K, Furuichi K, Yoneda I, Matsumura T, et al.
  • Journal Title: Int J Infect Dis. Volume: 91 Pages: 22-31
  • DOI: 10.1016/j.ijid.2019.11.003
  • NAID: 120006842044
  • Peer Reviewed / Open Access
• [Journal Article] IL-34-Dependent Intrarenal and Systemic Mechanisms Promote Lupus Nephritis in MRL-Faslpr Mice. (2019)
  • Author(s): Wada Y, Gonzalez-Sanchez HM, Weinmann-Menke J, Iwata Y, Ajay AK, Meineck M, Kelley VR.
  • Journal Title: J Am Soc Nephrol. Volume: 30 Issue: 2 Pages: 244-259
  • DOI: 10.1681/asn.2018090901
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Erythropoietin signal protected HUVEC from high glucose induced injury (2018)
  • Author(s): Yasuda Haruka、Iwata Yasunori、Nakajima Satoshi、Furuichi Kengo、Miyake Taito、Sakai Norihiko、Kitajima Shinji、Toyama Tadashi、Shinozaki Yasuyuki、Sagara Akihiro、Miyagawa Taro、Hara Akinori、Shimizu Miho、Kamikawa Yasutaka、Sato Kouichi、Oshima Megumi、Yoneda-Nakagawa Shiori、Kaneko Shuichi、Wada Takashi
  • Journal Title: Nephrology Volume: in press Issue: 7 Pages: 767-774
  • DOI: 10.1111/nep.13518
  • Peer Reviewed / Open Access
• [Journal Article] Gut microbiota-derived D-serine protects against acute kidney injury (2018)
  • Author(s): Yusuke Nakade, Yasunori Iwata, Takashi Wada, et al.
  • Journal Title: JCI Insight Volume: 18;3(20) Issue: 20 Pages: 97957-97957
  • DOI: 10.1172/jci.insight.97957
  • NAID: 120006733372
  • Peer Reviewed / Open Access
• [Presentation] 日本における腎臓・高血圧合併妊娠の最新の知見と今後の課題 (2021)
  • Author(s): 岩田恭宜, 古市賢吾, 横山仁, 和田隆志
  • Organizer: 2021国際母性内科学会
  • Invited
• [Presentation] 腎腸連関と腎臓病 (2021)
  • Author(s): 岩田恭宜, 中出祐介, 和田隆志
  • Organizer: 第５１回日本腎臓学会西部学術大会
  • Invited
• [Presentation] ループス腎炎における血清Autotaxin (ATX) および Phosphatidylserine-specific phospholipase A1 (PS-PLA1)値の意義 (2021)
  • Author(s): 岩田恭宜、矢冨裕、和田隆志
  • Organizer: 第33回腎と脂質研究会
• [Presentation] The gut-kidney axis in diabetic kidney disease (2020)
  • Author(s): 岩田恭宜、中出祐介、和田隆志
  • Organizer: 第63回日本糖尿病学会学術大会
  • Invited
• [Presentation] 細菌遺伝子情報の病態への関与 (2018)
  • Author(s): 岩田 恭宜
  • Organizer: 第６１回日本腎臓学会総会
  • Invited
• [Book] 臨床検査のガイドライン JSLM2021 検査値アプローチ/症候/疾患 (2022)
  • Author(s): 岩田恭宜、和田隆志
  • Total Pages: 5
  • Publisher: 宇宙堂八木書店