JP2016039814A - β−ラクタマーゼ耐性の質量分析測定 - Google Patents
β−ラクタマーゼ耐性の質量分析測定 Download PDFInfo
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Classifications
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- C—CHEMISTRY; METALLURGY
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- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
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- C12Q1/02—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving viable microorganisms
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
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Abstract
【解決手段】本発明は、β−ラクタム系抗生物質に対して微生物的に生成されたβ−ラクタマーゼの触媒効果、すなわち、β−ラクタム環の加水分解開裂によって、非常に簡単かつ迅速に、微生物耐性を測定することができる方法を提供する。この方法は、好適な基質(β−ラクタム系抗生物質またはカスタマイズされたβ−ラクタム誘導体のいずれか)を微生物の懸濁液に添加してから数時間後に、β−ラクタマーゼによって生じた基質の分解を直接質量分析手法で測定することによって、細菌の耐性を判定する。
【選択図】図1
Description
Claims (16)
- 微生物によるβ−ラクタマーゼの生成に基づいて前記微生物のβ−ラクタム耐性を判定するための方法であって、
前記微生物由来のβ−ラクタマーゼによる基質の酵素的分解を、残存する前記基質およびその分解生成物の質量分析スペクトルを取得することによって質量分析的に測定することを特徴とする方法。 - 前記基質の分子がβ−ラクタム環を含むことを特徴とする請求項1記載の方法。
- 前記基質がβ−ラクタム系抗生物質またはβ−ラクタム誘導体であることを特徴とする請求項2記載の方法。
- 前記基質が700〜1200原子質量単位の分子量を有することを特徴とする請求項1記載の方法。
- 前記基質の抗生物質効果が小さいことを特徴とする請求項1記載の方法。
- 前記基質の分子はアンカー基を有し、これにより溶液から前記基質の分子を抽出することを特徴とする請求項1記載の方法。
- 前記アンカー基がビオチン基または6−Hisタグであることを特徴とする請求項6記載の方法。
- いくつかのタイプの前記基質の分解生成物を同時に測定することを特徴とする請求項1記載の方法。
- さまざまなタイプの前記基質が、その分解パターンによって異なるβ−ラクタマーゼの分類の同定が可能となるようカスタマイズされていることを特徴とする請求項8記載の方法。
- β−ラクタム環周囲にある前記異なるタイプの基質それぞれが、異なる抗生物質の空間的形状を模していることを特徴とする請求項9記載の方法。
- 前記基質の分解の反応速度が測定されることを特徴とする請求項1記載の方法。
- 前記微生物を血液または血液培養物から取得することを特徴とする請求項1記載の方法。
- 前記の残存する基質およびその分解生成物の量をマトリックス支援レーザー脱離によるイオン化で質量分析により測定することを特徴とする請求項1記載の方法。
- 微生物によるβ−ラクタマーゼの生成に基づいて前記微生物のβ−ラクタム耐性を判定するための方法であって、
(a) 前記β−ラクタマーゼにより分解され得る少なくとも1つの基質からなる溶液を前記微生物に添加する工程と、
(b) 前記溶液を所定の時間、所定の温度で培養する工程と、
(c) 残存する前記基質及びその分解生成物を含む前記溶液を、前記微生物から分離する工程と、
(d) 前記溶液の質量分析スペクトルを取得する工程と、
を含むことを特徴とする方法。 - 微生物によるβ−ラクタマーゼ生成に基づいて前記微生物のβ−ラクタム耐性を質量分析により判定するための消耗品パック(キット)であって、
前記パックに、前記微生物由来のβ−ラクタマーゼにより酵素的に分解することができる基質が含まれることを特徴とするパック。 - 請求項1記載の方法で取得された前記質量分析スペクトルを評価することを特徴するプログラム。
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HUE062700T2 (hu) | 2010-08-19 | 2023-11-28 | Univ Erasmus Med Ct Rotterdam | Eljárások antibiotikum-rezisztencia meghatározására mikroorganizmusokban |
US9689021B2 (en) * | 2011-10-14 | 2017-06-27 | Université de Liège | Method for measuring beta-lactam antibiotics |
WO2013182647A2 (en) | 2012-06-06 | 2013-12-12 | Idmic Sa | Method for detecting susceptibility of microorganisms to chemical agents |
EP2778232A1 (en) * | 2013-03-12 | 2014-09-17 | Universität Heidelberg | Method for the detection of multiresistant gram-negative bacteria |
EP2981830B1 (en) | 2013-04-04 | 2019-04-03 | Erasmus University Medical Center Rotterdam | Mass spectrometric determination of drug resistance |
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CZ2013473A3 (cs) | 2013-06-20 | 2014-11-26 | Univerzita Karlova v Praze, Lékařská fakulta v Plzni | Způsob detekce beta-laktamáz gramnegativních bakterií hmotnostní spektrometrií |
CN103645273B (zh) * | 2013-12-12 | 2015-12-30 | 宁波诺威医疗器械有限公司 | β-内酰胺类抗生素耐药性的检测方法、系统及其应用 |
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US20180282780A1 (en) * | 2017-03-29 | 2018-10-04 | Specific Technologies, LLC | Susceptibility and resistance of microorganisms |
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Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006088381A1 (en) * | 2005-02-15 | 2006-08-24 | Syft Technologies Limited | In vitro evaluation of micro-organisms and their antimicrobial agent susceptibilities |
US20080009029A1 (en) * | 2006-05-09 | 2008-01-10 | Bruker Daltonik Gmbh | Mass spectrometric measurement of microbial resistances |
WO2010067358A2 (en) * | 2008-12-08 | 2010-06-17 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Methods and kits for direct detection and susceptibility profiling of beta-lactam resistant bacteria |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5641623A (en) * | 1995-01-04 | 1997-06-24 | Martin; Mark T. | Electrochemiluminescence assay |
US7291480B2 (en) * | 2002-03-13 | 2007-11-06 | Black Jennifer A | Device and method for detecting antibiotic-inactivating enzymes |
DE102009032649B4 (de) | 2009-07-10 | 2017-12-21 | Bruker Daltonik Gmbh | Massenspektrometrische Identifizierung von Mikroben nach Unterarten |
DE102009033368B4 (de) | 2009-07-16 | 2023-01-26 | Bruker Daltonics GmbH & Co. KG | Massenspektrometrische Sepsisdiagnose |
DE102010023452B4 (de) * | 2010-06-11 | 2012-11-08 | Bruker Daltonik Gmbh | Massenspektrometrische Messung von β-Lactamase-Resistenzen |
CN102033102A (zh) * | 2010-10-13 | 2011-04-27 | 中国科学院上海有机化学研究所 | 高通量基质辅助激光解析-质谱法筛查奶类制品中β-内酰胺酶类解抗剂 |
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2006088381A1 (en) * | 2005-02-15 | 2006-08-24 | Syft Technologies Limited | In vitro evaluation of micro-organisms and their antimicrobial agent susceptibilities |
US20080009029A1 (en) * | 2006-05-09 | 2008-01-10 | Bruker Daltonik Gmbh | Mass spectrometric measurement of microbial resistances |
WO2010067358A2 (en) * | 2008-12-08 | 2010-06-17 | Yissum Research Development Company Of The Hebrew University Of Jerusalem Ltd. | Methods and kits for direct detection and susceptibility profiling of beta-lactam resistant bacteria |
Non-Patent Citations (10)
Title |
---|
APLIN, R.T. ET AL.: ""USE OF ELECTROSPRAY MASS SPECTROMETRY TO DIRECTLY OBSERVE AN ACYL ENZYME INTERMEDIATE IN BETA-LACTA", FEBS LETTERS, vol. Vol.277, No.1-2, JPN5013007385, 17 December 1990 (1990-12-17), pages 212 - 214, ISSN: 0003723390 * |
JUNG, C.M. ET AL.: ""Acetylation of fluoroquinolone antimicrobial agents by an Escherichia coli strain isolated from a m", J. APPL. MICROBIOL., vol. 106, no. 2, JPN6015014065, February 2009 (2009-02-01), pages 564 - 571, ISSN: 0003445821 * |
LERICHE, T. ET AL.: ""An experimental comparison of electrospray ion-trap and matrix-assisted laser desorption/ionization", RAPID COMMUN. MASS SPECTROM., vol. 15, no. 8, JPN6015045386, August 2001 (2001-08-01), pages 608 - 614, ISSN: 0003594493 * |
LEWIS, E.R. ET AL.: ""A point mutation leads to altered product specificity in beta-lactamase catalysis."", PROC. NATL. ACAD. SCI. USA, vol. 94, no. 2, JPN6014027715, 21 January 1997 (1997-01-21), pages 443 - 447, ISSN: 0003723388 * |
LIESENER, A. ET AL.: ""Monitoring enzymatic conversions by mass spectrometry: a critical review."", ANAL. BIOANAL. CHEM., vol. 382, no. 7, JPN6015014066, August 2005 (2005-08-01), pages 1451 - 1464, ISSN: 0003445822 * |
NIU, G. ET AL.: ""SanJ, an ATP-dependent picolinate-CoA ligase, catalyzes the conversion of picolinate to picolinate-", METAB. ENG., vol. 8, no. 3, JPN6014027709, May 2006 (2006-05-01), pages 183 - 195, XP024946970, ISSN: 0003723392, DOI: 10.1016/j.ymben.2005.12.002 * |
SAVES, I. ET AL.: ""MASS SPECTRAL KINETIC STUDY OF ACYLATION AND DEACYLATION DURING THE HYDROLYSIS OF PENICILLINS AND C", BIOCHEMISTRY, vol. 34, no. 37, JPN5013007384, 1 September 1995 (1995-09-01), pages 11660 - 11667, XP055005564, ISSN: 0003723389, DOI: 10.1021/bi00037a003 * |
WELLING, G.W. ET AL.: ""Determination of enzyme activity by high-performance liquid chromatography."", J. CHROMATOGR. B BIOMED. APPL., vol. Vol.659, No.1-2, JPN6014027711, 23 September 1994 (1994-09-23), pages 209 - 225, ISSN: 0003723391 * |
YAZAWA, K. ET AL.: ""Inactivation of kanamycin A by phosphorylation in pathogenic Nocardia."", MICROBIOL. IMMUNOL., vol. 35, no. 1, JPN6015014069, January 1991 (1991-01-01), pages 39 - 48, XP009144264, ISSN: 0003723387 * |
大川光央、外5名: "「急性単純性膀胱炎患者からのβ-lactamase産生菌の分離頻度」", 泌尿器科紀要, vol. 33, no. 11, JPN6014027707, November 1987 (1987-11-01), pages 1800 - 1805, ISSN: 0003445820 * |
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