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Applications of MALDI-TOF Mass Spectrometry in Clinical Microbiology
Biomed Sci Letters 2022;28:145-156
Published online September 30, 2022;  https://doi.org/10.15616/BSL.2022.28.3.145
© 2022 The Korean Society For Biomedical Laboratory Sciences.

Kyeong Seob Shin1,* and Jonghwa Yum2,†,*

1Department of Laboratory M edicine, Chungbuk National University College of Medicine, Cheongju 28644, Korea
2Department of Clinical Laboratory Science, Dongeui University, Busan 47340, Korea
Correspondence to: Jonghwa Yum. Department of Clinical Laboratory Science, Dong-eui University, Busan 47340, Korea.
Tel: +82-51-890-2682, Fax: +82-505-182-6877, e-mail: auxotype@deu.ac.kr
*Professor.
Received August 24, 2022; Revised September 13, 2022; Accepted September 14, 2022.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
 Abstract
Over the past few decades, few technologies have had a greater impact on clinical microbiology laboratories than matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF MS). The MALDI-TOF MS is a fast, accurate, and low-cost and efficient method of microbial identification. This technology generates characteristic mass spectral fingerprints that is a unique signature for each microorganism, making it an ideal method for accurate identification at the genus and species levels of both bacterial and fastidious microorganism such as anaerobes, mycobacterium and fungi etc. In addition, MALDI-TOF MS has been successfully used in microbial subtyping and susceptibility tests such as determination of resistance genes. In this study, the authors summarized the application of MALDI-TOF MS in clinical microbiology and clinical research and explored the future of MALDI-TOF MS.
Keywords : MALDI-TOF MS, Clinical microbiology, Application, Identification, Subtyping, Susceptibility
꽌 濡

Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS)뒗 媛곴컖쓽 誘몄깮臾쇰줈遺꽣 깮湲 룆듅븯怨 듅吏뺤쟻씤 吏덈웾 뒪럺듃읆 吏臾(mass spectra fingerprint)쓣 씠슜븯뿬 誘몄깮臾쇱쓣 룞젙븷 닔 엳뒗 슚쑉쟻씤 諛⑸쾿씠떎. 씠 諛⑸쾿 鍮좊Ⅸ 諛섏쓳떆媛꾧낵 젙솗븳 寃곌낵瑜 蹂댁씠誘濡 씠긽쟻씤 誘몄깮臾 룞젙 諛⑸쾿씠씪 븷 닔 엳쑝硫, 媛源뚯슫 誘몃옒뿉 誘몄깮臾쇱쓽 븘삎 遺꾨쪟(subtyping)굹 궡꽦쓽 寃異쒖뿉룄 留롮씠 씠슜맆 寃껋씠떎.

吏덈웾 遺꾩꽍(Mass spectrometry, MS) 닔떗뀈 쟾遺꽣 솕븰 遺꾩빞뿉꽌 궗슜릺뼱 솕쑝硫, 1975뀈뿉 Anhalt and Fenselau (1975)뿉 쓽빐 꽌濡 떎瑜 醫(species)쓽 꽭洹 異붿텧臾쇱뿉꽌 룆듅븳 吏덈웾 뒪럺듃읆쓣 蹂닿퀬븳 寃껋씠 誘몄깮臾쇱쓽 듅꽦솕뿉 泥섏쓬 씠슜븳 寃껋씠떎. 씠썑 꽭洹좎쓽 봽濡쒗뙆씪(profiling)濡 遺꽣 遺꾩옄 몴吏옄(molecular biomarker)瑜 씠삩쑝濡 留뚮뱾 닔 엳뒗 떎뼇븳 씠삩솕(ionization) 湲곗닠씠 媛쒕컻릺뿀吏留 씠 떆湲곗뿉뒗 꽭洹좎쓽 吏吏(lipid)怨 媛숈 遺꾩옄웾씠 옉 臾쇱쭏留뚯쓣 씠삩솕 븷 닔 엳뿀떎. 떒諛깆쭏怨 媛숈 遺꾩옄웾씠 겙 깮泥대텇옄(biomolecule)瑜 씠삩솕븯湲 쐞빐꽌뒗 넂 뿉꼫吏媛 븘슂븳뜲, 넂 뿉꼫吏瑜 궗슜븯硫 깮泥대텇옄媛 삩쟾븳 긽깭(intact)濡 쑀吏릺吏 븡怨 뙆愿대릺뼱 깮泥대텇옄쓽 援ъ꽦쓣 삁痢≫븷 닔媛 뾾떎. 1980뀈 썑諛 Tanaka 諛 Fenn (Tanaka et al., 1988; Fenn et al., 1989)뿉 쓽빐 떒諛깆쭏怨 媛숈 嫄곕 깮泥대텇옄瑜 삩쟾븳 긽깭濡 쑀吏븳 梨 씠삩솕 떆耳 吏덈웾쓣 痢≪젙븷 닔 엳뒗 MALDI 諛 electrospray ionization 媛숈 湲고솕(soft ionization) 湲곗닠씠 媛쒕컻릺뿀쑝硫 씠썑 TOF analyzer 寃고빀븯뿬 MALDI-TOF媛 릺뿀떎. 1996뀈 Holland 벑 (Holland et al., 1996) MALDI-TOF瑜 씠슜븯뿬 꽭洹좎쓽 뒪럺듃읆 吏臾몄쓣 泥섏쓬 蹂닿퀬븯떎. 씠 떆룄濡 냽(genus) 諛 醫(species) 닔以뿉꽌 꽭洹좎쓣 룞젙븯怨좎옄 븯뒗 떎뼇븳 떆룄뱾(Claydon et al., 1996; Haag et al., 1998)씠 엳뿀怨 쁽옱뒗 꽭洹좎쓽 룞젙뿉 꼸由 씠슜릺怨 엳떎.

씠 뿰援ъ뿉꽌 옄뒗 MALDI-TOF MS쓽 湲곗닠쟻 썝由ъ 誘몄깮臾 遺꾩빞뿉꽌 MALDI-TOF MS媛 쟻슜릺뒗 遺꾩빞뿉 빐 議곗궗븯뿬 怨좎같븯떎. 듅엳 꽭洹좉낵 吏꾧퇏쓽 룞젙뿉꽌 MALDI-TOF MS쓽 꽦뒫쓣 븣븘蹂닿퀬, 삁븸씠굹 떎뼇븳 엫긽 寃泥댁뿉꽌 吏곸젒 쟻슜븳 삁뿉 빐꽌룄 議곗궗븯떎. 洹 쇅 븘삎쓽 遺꾨쪟굹 빆洹좎젣 궡꽦 뿰援ъ뿉 MALDI-TOF MS쓽 쟻슜뿉 빐 븣븘蹂닿퀬 븵쑝濡 MALDI-TOF MS쓽 엫긽誘몄깮臾 遺꾩빞뿉꽌 諛쒖쟾 諛⑺뼢뿉 빐 媛꾨왂엳 湲곗닠븯떎.

蹂 濡

1. MADLI-TOF MS쓽 썝由

1) MALDI-TOF MS쓽 湲곗닠쟻 씠빐

吏덈웾 遺꾩꽍湲(mass spectrometer)뒗 湲곕뒫쟻쑝濡 3媛吏 遺쐞濡 援ъ꽦릺뒗뜲, 1) 寃泥댁쓽 遺꾩옄(sample molecule)瑜 씠삩솕븯怨 湲곗껜濡 留뚮뱶뒗 씠삩 source 遺쐞(ionization: MALDI in MALDI-TOF MS), 2) 吏덈웾-쟾븯 鍮(mass/charge ratio, m/z)뿉 뵲씪 遺꾩옄 씠삩쓣 遺꾨━븯뒗 吏덈웾 遺꾩꽍湲(mass analyzer: TOF analyzer in MALDI-TOF MS), 3) 遺꾨━맂 씠삩쓣 寃異쒗븯뒗 寃異쒓린(detector)濡 援ъ꽦맂떎(mass spectrometry). MADI뒗 씠삩솕瑜 븯뒗 븳 媛吏 諛⑸쾿쑝濡 떒諛깆쭏怨 媛숈 嫄곕븳 鍮꾪쐶諛쒖꽦 깮泥대텇옄瑜 삩쟾븳 긽깭(intact)濡 씠삩솕 湲고솕(soft ionization)떆궎뒗 湲곗닠씠떎(Tanaka et al., 1988; Cherkaoui et al., 2010). MALDI뒗 遺遺 떒룆쑝濡 쟾븯瑜 씍 씠삩쓣 留뚮뱾硫 MADLI뿉 쓽빐 留롮 닔쓽 떒諛깆쭏 뵾겕濡 援ъ꽦맂 뒪럺듃읆씠 깮湲곕濡 떒諛깆쭏 遺꾩꽍뿉 쑀슜븯寃 씠슜맆 닔 엳떎. MALDI 遺꾩꽍뿉꽌 궗슜릺뒗 留ㅽ듃由뒪뒗 遺꾩꽍臾쇱쭏怨 꽎뿬 寃곗젙솕릺怨 젅씠媛 寃泥댁뿉 議곗궗맆 븣 젅씠쓽 媛뺥븳 뿉꼫吏瑜 씉닔븯뿬 寃泥닿 옉 議곌컖쑝濡 源⑥吏 븡怨 삩쟾븳 긽깭쓽 떒諛깆쑝濡 議댁옱븯룄濡 븯뒗 뿭븷쓣 븳떎(Fig. 1). 留ㅽ듃由뒪뒗 옉 遺꾩옄웾쓽 궛(acid)씠硫 遺꾩꽍븯뒗 깮泥대텇옄뿉 뵲씪 援ъ꽦씠 떎瑜몃뜲, 媛옣 꼸由 궗슜릺뒗 留ㅽ듃由뒪뒗 2,5-dihydroxybenzoic acid (DHB) a-cyano-4-hydroxycinnamic acid (CHCA), sinapinic acid (SA), ferulic acid (FA) 벑씠硫 FA, SA, CHCA媛 슚怨쇱쟻씤 떒諛 몴吏옄쓽 寃異쒖뿉 씠슜맂떎(Fenselau and Demirev, 2001; Vaidyanathan et al., 2002; Williams et al., 2003). 떎젣濡 誘몄깮臾 寃泥닿 留ㅽ듃由뒪 꽎뿬 湲덉냽 몴硫 쐞뿉꽌 寃곗젙솕릺뒗뜲, 젅씠 議곗궗 썑 留ㅽ듃由뒪뒗 젅씠 뿉꼫吏瑜 媛뺥븯寃 씉닔븯怨 沅곴레쟻쑝濡 寃泥댁뿉 씠 뿉꼫吏瑜 쟾떖븯뿬 씠삩솕맖쑝濡쒖뜥 遺꾩꽍臾쇱쭏(analyte)쓣 깉李(desorption)怨 씠삩솕瑜 떆궎뒗 뿭븷쓣 븳떎(Fig. 1). 遺꾩꽍븯젮뒗 臾쇱쭏(analytes) MALDI뿉 쓽빐 遺遺 떒룆쑝濡 쟾븯瑜 씍 씠삩씠 릺硫 씠삩솕맂 遺꾩꽍臾쇱쓣 쟾湲곗옣뿉꽌 利앺룺(acceleration)떆궓 썑 吏꾧났愿(臾댁쟾湲곗옣)쑝濡 蹂대궡硫 吏덈웾 寃異쒓린(mass detector)뿉 룄떖븷 븣源뚯 鍮꾪뻾븯寃 맂떎. 씠븣 떒諛 議곌컖뱾쓽 mass/charge (m/z)뿉 쓽빐 遺꾩옄웾씠 옉 닚꽌濡(time of flight, TOF) 吏덈웾 寃異쒓린뿉 룄떖븯怨 誘몄깮臾쇱뿉 뵲씪 듅씠븳 뒪럺듃읆씠 깮꽦맂떎. 寃異쒓린뿉 룄李⑺븯뒗뜲 嫄몃━뒗 떆媛(TOF) 깮泥 遺꾩꽍臾쇱쭏(bioanalyte)쓽 吏덈웾(mass)怨 쟾븯(charge, z)뿉 醫뚯슦릺뒗뜲 m/z쓽 젣怨깃렐뿉 鍮꾨븳떎. m/z 씠삩쓽 媛뺣룄뿉 쓽빐 吏덈웾쓽 뒪럺듃읆씠 諛쒖깮븯뿬 씠 뒪럺듃읆 誘몄깮臾 留덈떎 듅씠븯뿬 湲곗 誘몄깮臾쇱쓽 뜲씠꽣踰좎씠뒪 鍮꾧탳븯寃 릺硫 誘몄깮臾쇱쓣 젙솗븯寃 룞젙븷 닔 엳寃 맂떎(Fig. 2). 넻긽쟻쑝濡 1,000뿉꽌 20,000 m/z궗씠쓽 뒪럺듃읆쓣 遺꾩꽍븯寃 맂떎(Croxatto et al., 2012).

Fig. 1. Ionization of analytes by MALDI. After irradiation by laser beam, analytes & matrix were desorption and ionization with intact form (soft ionization) from target plate (from Creative Proteomics: https://www.creative-proteomics.com).
Fig. 2. General schematics for MALDI-TOF MS analysis of microbiological isolates. Samples are added to the MALDI plate, overlaid with matrix, and dried. After the sample is bombarded by the laser, the sample and matrix were desorption and ionization. The generated ions are separated based on their mass-to-charge ration via a TOF tube, and spectra of these ions is generated and analyzed by the MS software. This profile is subsequently compared to a database of reference MS spectra (Clark et al., 2013, Clin Microbiol Rev).

2) 誘몄깮臾쇱쓽 룞젙怨 諛붿씠삤 留덉빱뿉 븳 뜲씠꽣 遺꾩꽍

삩쟾븳(intact) 꽭洹좎뿉꽌 MALDI-TOF 뒪럺듃읆뿉꽌 寃異쒕맂 諛붿씠삤 留덉빱뒗 遺遺 遺꾩옄웾씠 15 kDa 씠븯씤 以묎컙 냼닔꽦 떒諛깆쑝濡 꽭룷 궡뿉꽌 뭾遺븯硫 젅諛섏씠 由щ낫醫(ribosomal) 떒諛(Arnold et al., 1999)씠떎. 由щ낫醫 떒諛깆 뭾遺븯怨(꽭룷 珥 떒諛깆쓽 20% 씠긽) 留ㅼ슦 湲곕낯쟻씤 떒諛깆쑝濡 MALDI 怨쇱젙뿉꽌 슚怨쇱쟻쑝濡 씠삩솕맆 닔 엳떎(Krause et al., 1999). Escherichia coli뿉꽌 떆뻾븳 由щ낫醫 떒諛 씠쇅쓽 떒諛깆뿉뒗 빑궛怨 寃고빀맂 뭾遺븳 떒諛(DbhA and DbhB)씠굹 cold-shock protein (CspA, CspC, CspE) 벑씠 엳떎(Ryzhov and Fenselau 2001). 궡紐⑤꽟씪쓽 MALDI-TOF MS 遺꾩꽍뿉꽌 뼸 諛붿씠삤 留덉빱뿉 쓽븯硫 遺遺꾩 由щ낫醫 떒諛깆쓣 룷븿븯뒗 湲곕낯쟻씤 떒諛깆씠굹, DNA 삉뒗 RNA 寃고빀릺뼱 엳뒗 벑쟾젏(isoelectric point)씠 9 씠긽씤 떒諛깆씠뿀떎. 븳렪 꽭洹좎쓽 씪諛섏쟻씤 룞젙뿉 쟻젅븳 떒諛깆쓽 MALDI-TOF 뒪럺듃읆 쇅遺솚寃쎌뿉 쓽빐 誘몄꽭븳 쁺뼢쓣 諛쏅뒗 븯슦뒪 궎븨(house-keeping) 湲곕뒫쓣 媛뽯뒗 蹂댁쟾(conserved) 떒諛깆뿉 쓽빐 援ъ꽦맂떎.

誘몄깮臾쇱쓣 듅꽦솕 븷 닔 엳뒗 MALDI-TOF MS쓽 諛⑸쾿뿉뒗 씪諛섏쟻쑝濡 2媛吏媛 엳뒗뜲 븯굹뒗 吏덈웾 뒪럺듃읆쓣 吏臾(fingerprints) 뜲씠꽣踰좎씠뒪 鍮꾧탳븯뒗 寃껋씠怨 삉 븯굹뒗 봽濡쒗뀒샂(proteome) 뜲씠꽣踰좎씠뒪 몴吏옄쓽 吏덈웾(biomarker mass)쓽 씪移 젙룄瑜 鍮꾧탳븯뒗 寃껋씠떎. 泥 踰덉㎏ 諛⑸쾿 삩쟾븳 꽭룷뿉꽌 뼸 룆듅븳 뒪럺듃읆쓣 湲곗〈뿉 엳뒗 吏臾 씪씠釉뚮윭由(fingerprint libraries) 鍮꾧탳븯뒗 寃껋씠떎. 씠 諛⑸쾿 鍮좊Ⅴ怨 媛꾨떒븯硫 吏꾨떒寃궗뿉꽌 돺寃 쟻슜씠 媛뒫븯怨 誘몄깮臾쇱쓽 룞젙뿉 궗슜븯뒗 룆듅븯怨 蹂댁〈쟻씤 뵾겕濡 援ъ꽦릺뒗 뜲씠꽣踰좎씠뒪瑜 留뚮뱾湲 렪由ы븯뿬 긽뭹솕릺뼱 씠슜맆 닔 엳떎(Carbonnelle et al., 2007). 몢 踰덉㎏ 諛⑸쾿 쑀쟾옄 닚꽌媛 遺꾩꽍릺뼱 遺꾩옄웾씠 삁痢〓릺뒗 떒諛깆쭏怨 뒪럺듃읆뿉 엳뒗 떒諛깅텇옄쓽 吏덈웾쓣 鍮꾧탳븯뿬 誘몄쓽 誘몄깮臾쇱쓣 룞젙븯뒗 諛⑸쾿(Demirev et al., 1999)쑝濡 二쇰줈 뿰援ъ슜쑝濡 씠슜맆 닔 엳떎.

2. 엫긽誘몄깮臾 遺꾩빞뿉꽌 MALDI-TOF MS 쟻슜

1) 꽭洹좎쓽 룞젙

쁽옱 遺遺꾩쓽 엫긽 寃궗떎뿉꽌 誘몄깮臾쇱쓽 룞젙 깮솕븰쟻 諛섏쓳怨 몴쁽삎 듅꽦, 諛곗뿉꽌 옄씪뒗 꽦긽, 洹몃엺뿼깋, 洹좎쭛씫쓽 紐⑥뼇뿉 뵲씪 룞젙븯뒗 寃껋씠 씪諛섏쟻씠떎. 씠뱾 諛⑸쾿 遺遺꾩쓽 媛먯뿼쓣 씪쑝궎뒗 洹좎쓣 젙솗븯寃 룞젙븷 닔 엳吏留 씠瑜 쐞빐꽌뒗 긽떦븳 떆媛 洹몃━怨 鍮꾩슜씠 븘슂븯硫 닕젴맂 寃궗씤젰씠 븘슂븯떎. MALDI-TOF 湲곗닠씠 洹좎쓽 룞젙뿉 씠슜릺硫 뾼泥궃 젙룄쓽 룞젙떆媛꾩쓣 떒異뺥븷 닔 엳뼱 웾 寃궗媛 媛뒫븷 肉먮쭔 븘땲씪 留ㅼ슦 젙솗븳 룞젙씠 媛뒫븯寃 릺뿀떎. 寃뚮떎媛 洹좎쓽 몴쁽븰쟻 듅吏뺤씠 쟻뼱 遺꾩옄쑀쟾븰쟻 諛⑸쾿쑝濡쒕쭔 吏꾨떒릺뿀뜕 꽭洹좎쓽 룞젙룄 媛뒫븯寃 릺뿀떎(Bizzini et al., 2011).

쁽옱 MALDI-TOF MS瑜 씠슜븳 꽭洹 룞젙湲곌 긽뭹솕릺뼱 씠슜릺怨 엳뒗뜲, 洹 怨쇱젙쓣 媛꾨왂엳 蹂대㈃ 씪諛섏쟻쑝濡 怨좎껜諛곗뿉꽌 옄 떊꽑븳 吏묐씫쓣 湲덉냽 뵆젅씠듃뿉 諛붾Ⅸ 썑뿉 湲곌린쉶궗뿉꽌 異붿쿇븳 留ㅽ듃由뒪(1.5 μL CHCA in 50% acetonitrile/2/5% trifluoroacetic acid for Bruker instrument; our laboratory)瑜 뵆젅씠듃 쐞뿉 泥④븳떎. 씠븣 꽭洹좎쓽 룞젙쑉쓣 넂씠湲 쐞빐 媛쒕몄궛(formic acid)瑜 泥④븯湲곕룄 븳떎. 寃泥댁 留ㅽ듃由뒪쓽 샎빀臾쇱쓣 뵆젅씠듃뿉꽌 嫄댁“븳 썑 MALDI-TOF MS 湲곌린뿉 옣李⑺븯怨 옉룞븯硫 洹좊쭏떎 듅吏뺤쟻씤 뒪럺듃읆씠 諛쒖깮븯怨 而댄벂꽣뿉 엳뒗 뜲씠꽣踰좎씠뒪 鍮꾧탳븯뿬 꽭洹좎쓣 룞젙븯寃 맂떎. 꽭洹좎쓽 룞젙뿉 씠슜릺怨 엳뒗 긽뭹솕맂 MALDI-TOF MS 湲곌린 李멸퀬 諛⑸쾿뱾怨 鍮꾧탳븳 떎뼇븳 뿰援 寃곌낵媛 엳뒗뜲 씠뱾쓣 Table 1뿉 젙由ы븯떎. 쁽옱 Bruker system (biotyper) VITEK MS system씠 媛옣 꼸由 궗슜릺怨 엳떎. 980媛쒖쓽 엫긽뿉꽌 遺꾨━맂 洹좎쓣 씠슜븯뿬 Bruker system쓣 寃利앺븳 뿰援 寃곌낵(van Veen et al., 2010)뿉꽌 MALDI-TOF MS뒗 꽭洹좉낵 吏꾧퇏쓽 92.2%瑜 젙솗븯寃 룞젙븯뿬 넻긽쟻씤 깮솕븰쟻 룞젙 떆뒪뀥쓽 83.1%蹂대떎 쓽誘 엳寃 슦닔븯떎(Table 1). 洹 醫낅퀎濡 蹂대㈃ 옣궡 꽭洹좎쓽 97.7%瑜 species(醫) 닔以뿉꽌 젙솗엳 룞젙븷 닔 엳뿀怨, 룷룄떦 鍮꾨컻슚 洹몃엺쓬꽦媛꾧퇏쓽 92%, Staphylococci쓽 94.3%, Streptococci쓽 84.8%, HACCEK group (Heamophilus, Actinobacillus, Cardiobacterium, Capnocytophaga, Eikenella, and Kingella)쓽 84%, yeast쓽 85.2%瑜 젙솗엳 룞젙븯떎. 븳렪 Seng 벑 (Seng et al., 2009) Bruker system쑝濡 1,660媛쒖쓽 꽭洹좎쓣 넻긽쟻씤 몴쁽븰쟻 룞젙 諛⑸쾿怨 鍮꾧탳븯쓣 븣 95.4%瑜 냽(genus) 닔以뿉꽌, 84.1%뒗 醫 닔以뿉꽌 젙솗엳 룞젙븯떎. 2010뀈 Cherkaoui (Cherkaoui et al., 2010)뒗 720 엫긽 寃泥대 룊媛븯쓣 븣 94.4%瑜 젙솗엳 룞젙븷 닔 엳뿀뒗뜲, Streptococci 삉湲곗꽦 洹좎뿉꽌留 꽦뒫씠 쓽誘 엳寃 궙븯怨 굹癒몄 넻긽쟻씤 洹좎 留ㅼ슦 젙솗븯寃 룞젙씠 릺뿀떎. 2015뀈 Lee 벑 (Lee et al., 2015) 249媛쒖쓽 삉湲곗꽦 엫긽 洹좎<瑜 VITEK MS system쑝濡 룞젙븯쓣 븣 냽 닔以뿉꽌 91.1%, 醫 닔以뿉꽌 83.9%瑜 젙솗븯寃 룞젙븷 닔 엳뿀쓬쓣 蹂닿퀬븯떎. 寃곕줎쟻쑝濡 쁽옱뿉꽌 MALDI-TOF MS쓽 뜲씠꽣踰좎씠뒪媛 뾽洹몃젅씠뱶릺뼱 씠쟾蹂대떎 젙솗븯寃 룞젙븷 닔 엳吏留 븘吏곴퉴吏 Streptococcus 諛 HACCEK group 洹몃━怨 삉湲곗꽦 洹좎쓽 醫 닔以뿉꽌 룞젙쓽 젙솗꽦 떎냼 뼥뼱吏 닔 엳떎.

Performance of routine identification of bacteria and yeasts by MALDI-TOF MS

Reference N Classification Genus level (%) Species level (%) MsId (%) NoId (%) Comments
van Veen et al. (2010) 980 Total 98.8 92 1.7 1.1 *
311 Enterobacteriaceae 100 97.7 1.7 1.1
88 Non-fermentative GN 94.3 92 1.1 4.6
261 GP cocci in cluster 100 94.3 0.4 0
165 GP cocci in chains 98.8 84.8 7.3 1.2
Enterococci 100 98.4 0 0
Hemolytic Streptococci 100 100 0 0
S. milleri 100 77.8 0 0
S. pneumoniae 100 86.4 0 0 **
Viridans Streptococci 90.5 9.5 57.1 9.5 **
94 HACCEK 96.8 84 0 3.2
61 Yeasts 96.7 85.2 3.3 3.2
Seng et al. (2009) 1,660 Total 95.4 85.2 1.7 2.8
Gram Positive 0.8 2.0
Gram negative 0.9 0.7
Cherkaoui et al. (2010) 720 Total 100 94 0.9
416 Enterobacteriaceae 99.8 0
80 Aerobic GN 97.5 1.25
111 Staphylococci 98.2 0.9
87 Aerobic GP 73.6 3.4 Poor yield for
Lee et al. (2015) 249 Total 91.1 83.9 0.4 8.4 Streptococcal species
157 Anaerobic GNR 98.1 94.9 0.6 1.3
56 Anaerobic GPR 78.6 76.8 0 21.4
26 Anaerobic GPC 76.9 65.4 0 23.1
10 Anaerobic GNC 90 0 0 10
Lee et al. (2017) 309 Total 88 87.4 0.6 11.3
158 Common Candida 100 100 0 0
23 C. neoformans 8.7/100* 8.7/100 0 91.3/0 FA/ACN additive
128 Uncommon yeasts 75.8 74.2 0.8 23.4

Abbreviations: N, sample number; MsId, misidentification; NoId, not identification; GNR, gram negative rod; GPR, gram positive rod; GPC, gram positive cocci; GNC, gram negative cocci; HACCEK, Haemophilus, Actinobacillus, Cardiobacterium, Capncytophagia, Eikenella, and Kingella; FA, formic acid; ACN, Acetonitrile

*Most case of misidentification either did not have reference spectra in the database or was related to mislabeling of specimen

**Most of misidentification case was viridans Streptococci or Streptococcus pneumoniae



MALDI-TOF MS瑜 씠슜븳 꽭洹좎쓽 룞젙뿉꽌 쓷엳 臾몄젣媛 릺뒗 洹좎 viridans Streptococci group, S. penumoniae 洹몃━怨 삉湲곗꽦 꽭洹좎씠 遺遺꾩씠硫(Seng et al., 2009; Cherkaoui et al., 2010; Blondiaux et al., 2010), 씪諛섏쟻쑝濡 臾몄젣媛 맆 닔 엳뒗 寃쎌슦瑜 Table 2뿉 젙由ы븯떎(Croxatto et al., 2012). 듅엳 viridans Streptococci (S. parasanguinis, S. mitis) S. penumoniae뒗 諛젒 愿젴 援(closed related group)쑝濡 씠뱾 洹좎쓽 李몄“ 뒪럺듃읆쓣 룷븿븯뒗 뜲씠꽣踰좎씠뒪媛 遺議깊븯뿬 쓷엳 떎瑜 洹좎쑝濡 룞젙씠 맆 닔 엳떎. Shigella쓽 뒪럺듃읆룄 E. coli 쑀궗븯뿬 옒紐 룞젙씠 맆 媛뒫꽦씠 넂떎(Seng et al., 2009). 븳렪 꽭룷踰 援ъ“瑜 源④린 뼱젮썙 떒諛깆쭏쓽 떊샇媛 遺덉땐븳 寃쎌슦媛 엳뒗뜲, 슚紐(yeast)瑜 源④린 쐞빐꽌뒗 異붽쟻씤 떒諛 異붿텧 怨쇱젙씠 븘슂븯떎. 洹몃━怨 S. pneumoniae, H. influenza, K. pneumoniae뿉꽌 罹≪뒓씠 議댁옱븯뿬 슚怨쇱쟻쑝濡 遺꾪빐릺吏 븡쑝誘濡 뒪럺듃읆쓽 吏덉씠 굹鍮 옒紐 룞젙씠 맆 媛뒫꽦씠 넂떎. Actinomyces, Gemella, Nocardia, Streptomyces 벑 씪諛섏쟻쑝濡 떒諛깆쭏쓽 뒪럺듃읆 떊샇媛 빟븯떎.

Common problems in routine identification of microorganism by MALDI-TOF MS

Problems Examples
Limit of resolution of the MALDI-TOF MS Viridans streptococci and S. pneumoniae
Similarities of spectra present in database Shigella spp. identified as E. coli
Absence or insufficient reference spectra in the database Propionibacterium acnes as Eubacterium brachy
closed related bacteria: S. pneumoniae and S. parasanguinis
Difficult to lyse cell wall structure Yeasts require protein extraction procedure
S. pneumoniae, H. influenzae, K. pneumoniae possess a capsule which prevent efficient lysis
Insufficient protein signal Actinomyces, Gemella, Nocardia and Streptomyces species usually display weak protein signal
Small amount of material sample Better signal for Enterobacteriaceae grown on blood agar vs MacConkey agar
Taxonomical discordances Stenotrophomonas maltophilia as Pseudomonas hibiscicola
Agrobacterium tumefaciens is synonymous of Rhizobium rhizogenes

(Croxatto et al., 2012, FEMS Microbiol Rev)



2) 吏꾧퇏쓽 룞젙

MALDI-TOF MS뿉 쓽븳 吏꾧퇏쓽 룞젙 슚紐⑦삎 吏꾧퇏怨 궗긽삎 吏꾧퇏(filamentous fungi)뿉꽌 李⑥씠媛 엳떎. 슚紐⑦삎 吏꾧퇏 떒諛깆쭏 異붿텧 怨쇱젙留 異붽븯硫 슦닔븳 꽦쟻쓣 蹂댁씠굹 궗긽삎 吏꾧퇏 븘吏 몴以솕맂 異붿텧 怨쇱젙씠굹 李멸퀬 뒪럺듃읆씠 遺議깊븳 떎젙씠뼱꽌 븘吏곴퉴吏 몴쁽븰쟻 듅꽦뿉 쓽빐 룞젙쓣 留롮씠 븯怨 엳떎. Marklein 벑 (Marklein et al., 2009)쓽 蹂닿퀬뿉 쓽븯硫 267삁쓽 엫긽뿉꽌 遺꾨━맂 슚紐⑦삎 吏꾧퇏 以 92.5%媛 냽 닔以뿉꽌 젙솗븯寃 룞젙릺뿀쑝硫, van Veen 벑 (2010)씠 蹂닿퀬뿉꽌뒗 85%쓽 슚紐⑦삎 吏꾧퇏씠 젙솗엳 룞젙릺뿀떎(Table 1). 븳렪 Lee 벑 (Lee et al., 2017)쓽 蹂닿퀬뿉 쓽븯硫 309媛쒖쓽 洹좎< 以 CandidaCryptococcus neoformans 媛숈 쓷엳 遺꾨━릺뒗 슚紐⑤뒗 紐⑤몢뿉꽌 젙솗엳 룞젙씠 릺뿀怨 쓷븯吏 븡 寃쎌슦뿉뒗 75.8%媛 醫 닔以뿉꽌 룞젙씠 릺뿀떎(Table 1). 洹몃━怨 紐⑤뱺 슚紐⑥쓽 룞젙뿉꽌뒗 떒諛깆쭏 異붿텧 떒怨꾨 異붽빐빞 젙솗븳 룞젙씠 媛뒫븯떎.

3) 엫긽 寃泥대줈 遺꽣 꽭洹좎쓽 吏곸젒 룞젙

MALDI-TOF MS뿉 쓽븳 洹좎쓽 룞젙 怨쇱젙뿉 떎뼇븳 엫긽 寃泥댁 쇅遺쓽 쁺뼢쓣 諛쏆 븡怨 몴以솕븯湲 쐞빐꽌뒗 寃利앸맂 諛곗뿉 諛곗뼇맂 吏묐씫쓣 씠슜븯뿬빞 븳떎(CLSI 2018). 洹몃윭굹 誘몄깮臾쇱뿉 쓽븳 諛곗뼇떆媛꾩쓣 以꾩씠湲 쐞빐 엫긽 寃泥대줈遺꽣 吏곸젒 洹좎쓽 룞젙븯젮뒗 떆룄媛 씠猷⑥뼱吏怨 엳떎. 씠뱾 寃泥 醫낅쪟뿉뒗 삁븸, 냼蹂, 뇤泥숈닔븸 諛 쓨닔 벑씠 엳쑝硫 씠뱾쓽 엫긽 寃泥대 吏곸젒 寃궗븷 븣쓽 떒젏 寃泥댁뿉꽌 洹좎쓽 냽룄(닔)媛 쟻떎뒗 寃껋씠떎. 뵲씪꽌 씠 떒젏쓣 洹밸났븯湲 쐞빐 留롮 뼇쓽 寃泥닿 븘슂븳뜲, 뿬湲곗꽌뒗 삁븸怨 냼蹂뿉 븳 뿰援щ뱾뿉 빐 븣븘蹂닿쿋떎.

(1) 삁븸諛곗뼇

삁瑜섍컧뿼 룞븞 꽭洹좎쓽 뼇 諛由щ━꽣(mL)떦 1~10 CFU 젙룄씠湲 븣臾몄뿉 삁븸쓣 吏곸젒 씠슜븷 닔뒗 뾾吏留 옄룞삁븸諛곗뼇湲곗뿉꽌 뼇꽦 떊샇瑜 蹂대궦 삁븸 蹂묒뿉뒗 諛由щ━꽣 떦 106~108 CFU씠 議댁옱븿쑝濡 씠뱾 寃泥대 씠슜븯硫 MALDI-TOF MS濡 洹좎쓽 吏곸젒 룞젙씠 媛뒫븯떎. 洹몃윭굹 삁븸諛곗뼇 蹂묒뿉뒗 떎뼇븳 臾쇱쭏뱾씠 엳쑝誘濡 듅蹂꾪븳 寃泥댁쓽 쟾 泥섎━媛 븘슂븯떎. 吏곸젒 삁븸諛곗뼇 蹂 寃궗쓽 쟾 泥섎━(pretreatment)뒗 3떒怨꾨줈 씠猷⑥뼱吏뒗뜲, 1) 삁븸꽭룷瑜 遺꾨━떆궎뒗 썝떖遺꾨━ 떒怨, 2) 쟻삁援 슜삁 떒怨 洹몃━怨 3) 꽭泥 떒怨꾧 룷븿맂떎(Croxatto et al., 2012). 理쒓렐뿉 뿰援щ맂 삁븸諛곗뼇 뼇꽦 寃泥댁뿉꽌 吏곸젒 룞젙븳 꽦쟻쓣 몴뿉 젙由ы븯떎(Table 3). 醫 닔以뿉꽌 씪移섎룄瑜 蹂대㈃ 洹몃엺쓬꽦 洹좎뿉꽌뒗 83~92.6% 젙룄濡 슦닔븯쑝굹, 洹몃엺뼇꽦 洹좎뿉꽌뒗 32~78%源뚯 떎뼇븯떎. 듅엳 Streptococci, coagulase negative Staphylococci 벑쓽 씪移섏쑉씠 궙븯떎. 湲고 삁븸쓣 닚닔 諛곗뼇븯吏 븡怨 吏곸젒 룞젙븯寃 릺硫 뿬윭 媛吏 洹좎씠 媛먯뿼릺뿀쓣 寃쎌슦뒗 룞젙씠 릺吏 븡뒗 媛뒫꽦씠 넂떎.

Performance of MALDI-TOF MS identification directly obtained from positive blood culture bottles

Reference study Sample (n) Blood culture system Concordant identification level (%) Species of difficult identification
Species Genus
Prod'hom et al. (2010) 126 Bactec 78% 79% S. mitis Group
GN:89% GN:89% Staphylococcus spp.
GP:72% GP:73%
La Scola and Raoult (2009) 599 Bactec 66% 66% Streptococcus spp.
GN:91% Polymicrobial samples
GP:49%
Ferreira et al. (2010) 300 Bactec 43% 72% S. mutans
GN:83% GN:97% Staphylococcus spp.
GP:32% GP:66
Jo et al. (2016) 208 Bactec 77.2% 81.8% Streptococcus spp.
GN: 92.6% CoNS
GP:73.9%

Abbreviations: GN, gram negative; GP, gram positive; G, group; CoNS, coagulase negative Staphylococci



(2) 냼蹂 諛곗뼇

鍮꾨눊湲곌퀎 媛먯뿼(urinary tract infection)쓣 媛뽯뒗 솚옄뒗 냼蹂 1 mL떦 105 CFU쓽 洹좎씠 議댁옱븯뒗 寃쎌슦媛 留롮쑝誘濡 MALDI-TOF MS濡 냼蹂쓣 吏곸젒 寃궗븯젮뒗 떆룄媛 留롮씠 씠猷⑥뼱吏怨 엳떎. 洹몃━怨 냼蹂쓣 吏곸젒 寃궗븳 뿰援ъ뿉꽌 MALDI-TOF MS쓽 遺꾩꽍뙋뿉뒗 1~2 μL留 궗슜릺硫, 냼蹂 궡뿉 엳뒗 諛깊삁援щ굹 쟻삁援ъ 媛숈 꽭룷쓽 쟾 泥섎━ 怨쇱젙쓽 臾몄젣濡 씤븯뿬 洹좎쓽 遺꾨━ 꽦쟻 궙븯떎. 洹몃젃吏留 Croxatto 벑 (2012) 냼蹂 궡 洹좎쓽 닔媛 107~108/mL 씠긽씠怨 쟻젅븳 寃泥댁쓽 쟾 泥섎━ 썑뿉뒗 醫(species) 떒怨꾩뿉꽌 젙솗엳 룞젙븯뒗 젙룄媛 69~70%씠뿀떎怨 蹂닿퀬븯떎.

3. 媛源뚯슫 誘몃옒뿉 엫긽誘몄깮臾 寃궗떎뿉꽌 MALDI-TOF MS쓽 쟻슜

1) 꽭洹좎쓽 븘삎 遺꾨쪟

젙솗븳 꽭洹좎쓽 룞젙怨 븘삎 遺꾨쪟뒗 媛먯뿼吏덊솚쓽 媛먯뿼愿由ъ뿉 留ㅼ슦 以묒슂븯떎. 몴쁽삎뿉 쓽븳 븘삎 遺꾨쪟뒗 遺꾨퀎젰씠 뼥뼱吏怨, 쟾넻쟻씤 遺꾩옄쑀쟾븰쟻 遺꾨쪟(molecular typing)뒗 鍮꾩슜怨 떆媛꾩쓣 룷븿븳 留롮 젣빟 슂씤씠 엳뼱 떎젣濡 떆뻾븷 닔 엳뒗 寃궗떎씠 쟻 떎젙씠떎. MALDI-TOF MS뒗 떒諛깆쭏쓽 留롮 뒪럺듃읆쓣 寃異쒗븿쑝濡 諛젒븯寃 愿젴맂 醫낆쓣 援щ퀎븯뿬 醫 닔以뿉꽌 룞젙븷 닔 엳쓣 肉 븘땲씪 븘醫(subspecies) 닔以뿉꽌룄 룞젙씠 媛뒫븯뿬 誘몄깮臾쇱쓽 븘삎 遺꾨쪟媛 媛뒫븯떎(Dieckmann et al., 2008; Williamson et al., 2008; Lartigue et al., 2009; Cherkaoui et al., 2010). PFGE (pulse field gel electrophoresis) 媛숈 쟾넻쟻씤 븘삎 遺꾨쪟 諛⑸쾿 닔뻾뿉 닔씪씠 嫄몃━硫 닕젴맂 寃궗옄 寃쏀뿕씠 留롮 뿰援ъ옄媛 븘슂븯떎. MALDI-TOF MS뒗 닔떆媛 궡뿉 遺꾨쪟媛 媛뒫븯硫 옱쁽꽦怨 삁誘쇰룄(sensitivity)룄 슦닔븯떎. 洹몃젃吏留 MALDI-TOF MS뿉 쓽븳 遺꾨쪟뒗 꽭洹좎쓽 룞젙怨 떖由 寃泥댁쓽 以鍮 諛 遺꾩꽍 諛⑸쾿씠 떖씪빞 븯怨 뿬윭 媛吏 寃궗 슂씤(parameter)瑜 理쒖쟻솕븯뒗 寃껋씠 젅쟻씠떎. 利 醫 닔以뿉꽌 룞젙 紐 媛쒖쓽 諛붿씠삤 留덉빱媛 씠슜릺굹 遺꾨쪟瑜 쐞븳 븘醫 닔以뿉꽌 룞젙 蹂대떎 留롮 옱쁽꽦 엳뒗 뵾겕肉먮쭔 븘땲씪 뒪럺듃읆쓣 遺꾩꽍븷 닔 엳뒗 留롮 뜲씠꽣踰좎씠뒪룄 븘슂븯떎(Dieckmann et al., 2008; Croxatto et al., 2012). 쁽옱源뚯 떎뼇븳 洹몃엺뼇꽦 諛 쓬꽦 꽭洹좎쓽 븘삎 遺꾨쪟뿉 MALDI-TOF MS瑜 씠슜븳 뿰援щ뱾씠 蹂닿퀬릺怨 엳떎. 몴쟻쑝濡 洹몃엺뼇꽦 꽭洹좎뿉꽌 硫붿튂떎由 궡꽦 솴깋 룷룄븣洹(methicillin-resistant Staphylococcus aureus, MRSA)瑜 룷븿븳 S. aureus쓽 븘삎 遺꾨쪟뿉 꽦怨듭쟻쑝濡 쟻슜븯쑝硫(Wolters et al., 2011), 洹 쇅 Streptococcus pneumoniae (Williamson et al., 2008), Group B Streptococci (Lartigue et al., 2009), Streptococcus pyogenes (Moura et al., 2008) 벑뿉 쟻슜븳 蹂닿퀬媛 엳떎. 洹몃엺쓬꽦 꽭洹좎뿉꽌뒗 Salmonella enterica (Kuhns et al., 2012), Escherichia coli (Clark et al., 2013), Klebsiella pneumoniae (Berrazeg et al., 2013)뿉꽌 쟻슜릺뿀쑝硫, 2015뀈뿉뒗 以묓솚옄떎뿉꽌 李쎄텗븯뒗 二쇱슂 썝씤 洹좎씤 Acinetobacter baumannii Pseudomonas aeruginosa (Spinali et al., 2015)뿉룄 쟻슜릺뿀떎. 븵쑝濡 蹂대떎 留롮 쟻젅븳 李몄“ 洹좎<쓽 뒪럺듃읆씠 뜲씠꽣踰좎씠뒪뿉 異붽릺怨 씠뱾쓣 빐꽍븷 닔 엳뒗 냼봽듃썾뼱媛 諛쒖쟾븯寃 릺硫 븵쑝濡 誘몄깮臾쇱쓽 븘삎 遺꾨쪟뒗 MALDI-TOF MS濡 泥대맆 媛뒫꽦씠 留ㅼ슦 넂떎(Biswas et al., 2016).

2) 빆洹좎젣 궡꽦쓽 寃異

빆洹좎젣 궡꽦쓽 利앷뒗 쁽옱 쓽猷뚯뿉꽌 留ㅼ슦 以묒슂븳 臾몄젣씠떎. 꽭洹좎뿉꽌 빆洹좎젣 媛먯닔꽦 삉뒗 궡꽦뿉 븳 議곌린 寃곗젙씠 솚옄쓽 移섎즺뿉 留ㅼ슦 以묒슂븯誘濡 MALDI-TOF MS瑜 씠슜븳 鍮좊Ⅸ 궡꽦 寃異쒖씠 슂援щ릺怨 엳떎. MALDI-TOF MS뒗 誘몄깮臾쇱쓽 룞젙뿉 留ㅼ슦 쑀슜븯뿬 留롮 엫긽 寃궗떎뿉 룄엯릺뼱 궗슜릺怨 엳뒗뜲, 2010뀈 씠썑뿉 빆洹좎젣 궡꽦쓽 寃異쒖뿉 MALDI-TOF MS瑜 쟻슜븯뒗 留롮 떆룄뱾씠 씠猷⑥뼱吏怨 엳떎. 씠 以묒뿉꽌 MALDI-TOF MS쓽 carbapenemase쓽 寃異쒖 엫긽誘몄깮臾 遺꾩빞뿉꽌 留ㅼ슦 겙 쁺뼢쓣 誘몄튂뒗 삁 以 븯굹濡 쁽옱 씪遺 寃궗떎뿉꽌 씠슜븯湲곕룄 븯怨 엳떎. 湲고 MRSA 諛 諛섏퐫留덉씠떊 궡꽦 옣援ш퇏(vancomycin resistant Enterococci, VRE)뿉꽌 궡꽦 諛붿씠삤 留덉빱쓽 寃異쒖뿉 븳 뿰援щ뱾씠 씠猷⑥뼱吏怨 엳떎(Hrabák et al., 2016).

(1) β-lactamase쓽 寃異

β-lactamase뒗 β-lactam 빆깮젣쓽 븘誘몃뱶 寃고빀(amide bond)瑜 媛닔遺꾪빐븯硫 18 Da쓽 遺꾩옄웾씠 利앷븯寃 릺怨, 媛닔遺꾪빐맂 썑 遺궛臾쇱씠 decarboxylation 릺硫 遺꾩옄웾씠 44 Da 媛먯냼븯寃 릺뼱 理쒖쥌쟻쑝濡 26 Da씠 媛먯냼븳 理쒖쥌궛臾(decarboxylated degradation product)씠 깮湲곌쾶 맂떎. β-lactam 빆깮젣쓽 듅씠븳 뒪럺듃읆쓣 MALDI-TOF MS濡 痢≪젙븷 닔 엳쑝誘濡, 빆깮젣 誘몄깮臾쇱쓣 룞떆뿉 諛곗뼇븳 썑뿉 痢≪젙븯寃 릺硫 β-lactamase쓽 議댁옱 뿬遺瑜 븣 닔 엳寃 맂떎(Sparbier et al., 2012). 利 β-lactamase媛 議댁옱븯硫 β-lactam 빆깮젣쓽 룆듅븳 뵾겕媛 26 Da씠 媛먯냼븳 쐞移섏뿉꽌 寃異쒗븷 닔 엳뒗 썝由ъ씠떎(Fig. 3: Hrabák et al., 2012). 씠 썝由щ 씠슜븯뿬 carbapenem쓣 媛닔遺꾪빐븯뒗 carbapenemase瑜 寃異쒗븯뒗 諛⑸쾿씠 蹂닿퀬릺뼱 寃궗떎뿉꽌 씠슜릺湲곕룄 븳떎(Burckhardt et al., 2011; Harbák et al., 2012). 듅엳 DHB 留ㅽ듃由뒪瑜 궗슜븳 MALDI-TOF MS濡 meropenem쓣 媛닔遺꾪빐븯뒗 carbapenemase瑜 寃異쒗븯뒗 諛⑸쾿씠 蹂닿퀬릺뿀떎(Hrabák et al., 2014). 寃뚮떎媛 β-lactamase 뼲젣젣瑜 씠슜븯硫 β-lactamase쓽 醫낅쪟룄 援щ퀎븷 닔 엳뒗뜲, clavulanic acid굹 tazobactam쓣 씠슜븯뿬 ESBL (extended-spectrum β-lactamase)쓣 援щ텇븷 닔 엳쑝硫 EDTA 諛 phenylboronic acid쓽 궗슜쑝濡 carbapenemase瑜 援щ텇븷 닔룄 엳떎. Carbapenemase瑜 MALDI-TOF MS濡 寃異쒗븯뒗 寃껋 엫긽뿉 留ㅼ슦 겙 쁺뼢쓣 以 닔 엳뒗뜲, 븘吏곴퉴吏 뒪럺듃읆쓽 빐꽍쓣 닔湲곕쾿쑝濡 븯湲 븣臾몄뿉 씪遺 寃궗떎뿉꽌留 吏꾪뻾븯怨 엳떎. 쁽옱 냼봽듃썾뼱媛 媛쒕컻 以묒씠湲 븯吏留 옄룞빐꽍 냼봽듃썾뼱[삁; Bruker, MBT STAR-BL]媛 媛쒕컻릺硫 carbapenemase쓽 寃異쒖씠 긽슜솕 맆 닔 엳쓣 寃껋씠떎.

Fig. 3. MALDI-TOF MS spectrum of meropenem, sodium salts of meropenm, and degradation products by carbapenemase. (A) Spectrum of meropenem solution, (B) Non-carbapenmase-producing isolate of Klebsiella pneumoniae, (C) carbapenemase (NDM) producing Escherichia coli, (D) carbapenemase (NDM) producing Acinetobacter baumannii. In C and D (carbapenemase producing), MALDI-TOF MS showed three new peak, which are a peak of hydrolysed meropenem-2Na+ (446.5 m/z from 428.6: 18 Da↑), two peak of decarboxylated meropenm-H+ (358.6 m/z from 384.6: 26 Da↓) and meropenem-2Na+ (380.5 m/z from 406.2: 26 Da↓) (Hrabák et al., 2012, J Clin Microbiol).

(2) MRSA 諛 VRE쓽 궡꽦 寃異

MSSA (methicillin-susceptible Staphylococcus aureus) MRSA瑜 MALDI-TOF MS濡 鍮좊Ⅴ寃 援щ퀎븯뒗 寃껋 엫긽誘몄깮臾 寃궗떎뿉꽌 留ㅼ슦 쑀슜븳 씪씠떎. 씠뱾쓣 援щ퀎븯湲 쐞빐 MRSA뿉 븳 룆듅븳 뵾겕媛 媛쒕컻릺뼱 媛먮퀎뿉 씠슜맂 뿰援(Edwards-Jones et al., 2000; Du et al., 2002)뱾씠 蹂닿퀬릺뿀吏留 븘吏곴퉴吏 MRSA뿉 듅吏뺤쟻씤 PBP2a瑜 寃異쒗븯뒗 寃껋 蹂닿퀬릺吏 븡븯떎. VRE瑜 寃異쒗븯젮뒗 MALD-TOF MS쓽 떆룄룄 씠猷⑥뼱吏怨 엳쑝硫, Griffin 벑 (2012) vanB VRE瑜 寃異쒗븯떎. 洹몃윭굹 븘吏곴퉴吏 VRE쓽 遺遺꾩쓣 李⑥븯뒗 vanA VRE瑜 寃異쒗븳 蹂닿퀬뒗 뾾뿀떎. 븵쑝濡 MRSA VRE 媛숈씠 떒씪 쑀쟾옄濡 궡꽦湲곗쟾쓣 굹궡뒗 洹좎쓣 MALDI-TOF MS濡 寃異쒗븯뒗 寃껋 留ㅼ슦 쑀슜븯湲 븣臾몄뿉 뜑 留롮 뿰援ш 씠猷⑥뼱吏 寃껋쑝濡 삁긽맂떎.

4. 뜑 癒 誘몃옒쓽 MALDI-TOF MS 쟻슜 湲곗닠

MALDI-TOF MS뒗 鍮좊Ⅴ怨 遺꾩꽍 怨쇱젙쓽 鍮꾩슜씠 졃븯硫, 떊猶고븷 留뚰븳 寃곌낵瑜 蹂댁씠誘濡 엫긽誘몄깮臾 寃궗떎뿉꽌 誘몄깮臾쇱쓽 룞젙쓽 몴以 諛⑸쾿씠 맆 寃껋씠떎. 洹몃━怨 誘몄깮臾쇱쓣 룞젙븷 肉먮쭔 븘땲씪 븘삎 遺꾨쪟 궡꽦 寃異쒖뿉 以묒젏쟻씤 뿰援ш 吏꾪뻾맆 寃껋씠떎. 寃뚮떎媛 MALDI-TOF MS쓽 湲곌린 諛 냼봽듃썾뼱쓽 諛쒖쟾 誘몄깮臾 遺꾩빞뿉꽌 옄룞솕瑜 媛뒫븯寃 븷 닔 엳쓣 寃껋씠떎(Schubert and Kostrzewa, 2016). 뜑 癒 誘몃옒뿉뒗 immunoaffinity MALDI-TOF MS瑜 寃고빀븳 immune-MALDI뿉꽌룄 듅씠룄(specificity)瑜 븳痢 넂씪 닔 엳쓣 寃껋씠떎(Sparbier et al., 2009). Imaging mass spectrometry (IMS)뒗 옄뿰怨꾩뿉 엳뒗 꽌濡 떎瑜 biomolecule쓽 遺꾩옄吏룄(molecular mapping)룄 媛뒫븷 寃껋씠떎(Walch et al., 2008). 뵲씪꽌 IMS 湲곗닠 뼱뼡 몴떇룄 뾾씠 議곗쭅뿉 엳뒗 떒諛깆쭏, 렔떚뱶, 냼遺꾩옄(small molecule), 꽭룷 諛섏쓳궛臾(cell metabolite), 吏吏 벑 떎뼇븳 遺꾩꽍泥(analyte)瑜 遺꾩꽍븷 닔 엳뼱 떎뼇븳 吏덊솚 뿰援ъ뿉 씠슜맆 닔 엳쓣 寃껋씠떎(M'Koma, 2014). 듅엳 IMS媛 誘몄깮臾 遺꾩빞뿉 쟻슜븯寃 릺硫 蹂묒썝泥댁 닕二 궗씠쓽 긽샇옉슜쓣 뿰援ы븷 닔 엳떎뒗 쓽誘몃줈 媛먯뿼쓽 옞옱쟻(potential) 몴吏옄瑜 諛쒓껄븷 닔룄 엳쓣 寃껋씠떎(Moore et al., 2014). 寃뚮떎媛 IMS뒗 洹좎< 궡(intra species), 洹좎< 媛(inter species) 洹몃━怨 꽌濡 떎瑜 洹좎< 媛(polymicrobial) 긽샇옉슜(interaction)쓣 議곗궗븷 닔룄 엳쓣 寃껋씠떎(Yang et al., 2012).

寃 濡

吏궃 닔떗 뀈 룞븞 MADI-TOF MS 蹂대떎 엫긽誘몄깮臾 떎뿕떎뿉 뜑 겙 쁺뼢쓣 겮移 湲곗닠 嫄곗쓽 뾾떎. MALDI-TOF MS뒗 鍮좊Ⅴ怨 젙솗븯硫 鍮꾩슜씠硫 슚쑉쟻씤 誘몄깮臾 룞젙 諛⑸쾿씠떎. 씠 湲곗닠 媛 誘몄깮臾쇱쓽 怨좎쑀븳 떊샇씤 듅吏뺤쟻씤 吏덈웾 뒪럺듃읆 吏臾몄쓣 깮꽦븯誘濡 꽭洹좎 臾쇰줎씠怨 삉湲곗꽦 誘몄깮臾, Mycobacterium 洹몃━怨 怨고뙜씠 벑 源뚮떎濡쒖슫 誘몄깮臾쇱쓽 냽怨 醫 닔以뿉꽌 젙솗븳 떇蹂꾩뿉 씠긽쟻씤 諛⑸쾿씠떎. 쁽옱源뚯 MALDI-TOF MS쓽 꽦뒫 룊媛 寃곌낵瑜 蹂대㈃ 엫긽쟻쑝濡 媛먯뿼쓣 씪쑝궎뒗 꽭洹좎쓽 룞젙 닔以 李멸퀬 諛⑸쾿씤 16S rRNA 뿼湲곗꽌뿴 遺꾩꽍쓣 젣쇅븯怨 媛옣 젙솗븳 寃곌낵瑜 굹궦떎. MADLI-TOF MS 쟻슜 닚닔 吏묐씫씠 븘슂븯떎뒗 떒젏씠 엳湲곕뒗 븯吏留 엫긽誘몄깮臾쇱뿉꽌 媛옣 以묒슂븳 寃泥댁씤 삁븸諛곗뼇씤 寃쎌슦뿉뒗 留ㅼ슦 슦닔븳 寃곌낵瑜 蹂댁씠誘濡 꽭洹 媛먯뿼利 솚옄瑜 議곌린뿉 吏꾨떒븯뒗뜲 留ㅼ슦 룄씠 맆 寃껋쑝濡 깮媛곷맂떎. 룞젙씠 源뚮떎濡쒖슫 誘몄깮臾쇱쓣 鍮좊Ⅴ怨 젙솗븯寃 룞젙븷 닔 엳떎뒗 寃껊룄 留ㅼ슦 겙 옣젏씠굹 븘吏곴퉴吏 뱶臾쇨쾶 遺꾨━릺嫄곕굹 깉濡쒖슫 誘몄깮臾쇱뿉 븳 뜲씠꽣踰좎씠뒪媛 뾾뒗 寃쎌슦뿉뒗 룞젙씠 릺吏 븡쑝誘濡 씠뱾뿉 븳 뜲씠꽣踰좎씠뒪쓽 솗옣씠 븘슂븯떎. 븳렪 洹좎쓽 룞젙쓣 꽆뼱꽌 돺怨 鍮좊Ⅴ寃 븘삎 援щ텇씠 媛뒫빐졇 洹 룞븞 뼱졄怨 삤옖 떆媛꾩쓽 냼슂濡 遺遺꾩쓽 寃궗떎뿉꽌 떆뻾븯吏 븡븯뜕 썝궡媛먯뿼쓽 李쎄텗뿉 븳 뿭븰議곗궗媛 떎떆媛꾩쑝濡 媛뒫븯寃 릺뼱 쓽猷뚭컧뿼愿由ъ뿉꽌룄 媛뺣젰븳 룄援ш 맆 寃껋씠떎. 寃뚮떎媛 MALDI-TOF MS뒗 궡꽦 쑀쟾옄 寃곗젙怨 媛숈 媛먯닔꽦 떆뿕뿉룄 꽦怨듭쟻쑝濡 궗슜릺怨 엳떎. 쁽옱뒗 씪遺 以묒슂븳 궡꽦 쑀쟾옄 寃곗젙뿉留 쟻슜릺吏留 踰붿쐞媛 솗릺硫 媛먯뿼 솚옄쓽 移섎즺뿉 쉷湲곗쟻씤 쟾솚씠 씠猷⑥뼱吏 寃껋씠씪 湲곕맂떎.

寃곕줎쟻쑝濡 MALDI-TOF MS뒗 遺遺꾩쓽 꽭洹좎쓣 鍮좊Ⅴ怨 젙솗븯寃 룞젙븷 닔 엳쓣 肉먮쭔 븘땲씪 븘삎쓣 룞젙븯怨 以묒슂븳 빆洹좎젣 궡꽦 쑀쟾옄瑜 吏꾨떒븷 닔 엳뒗 옒엳뒗 룄援щ줈 엫긽誘몄깮臾 寃궗쓽 諛쒖쟾뿉 쉷湲곗쟻씤 쟾湲곌 맆 寃껋씠 솗떎븯떎. 씠 뿰援ъ뿉꽌 옄뒗 엫긽誘몄깮臾쇳븰 諛 誘몄깮臾 뿰援ъ뿉꽌 MALDI-TOF MS쓽 쟻슜 諛 븵쑝濡 쟻슜맆 닔 엳뒗 遺꾩빞뿉 빐 븣븘蹂댁븯쑝硫 엫긽誘몄깮臾 寃궗떎뿉 醫낆궗븯뒗 뿰援ъ옄뱾뿉 쑀씡븳 옄猷뚭 맆 닔 엳湲곕 湲곕빐 蹂몃떎.

ACKNOWLEDGEMENT

None.

CONFLICT OF INTEREST

The authors declare no conflict of interest.

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