Multilocus Sequence Typing (MLST) Genotypes of Candida glabrata Bloodstream Isolates in Korea: Association With Antifungal Resistance, Mutations in Mismatch Repair Gene (Msh2), and Clinical Outcomes.
Multilocus Sequence Typing (MLST) Genotypes of Candida glabrata Bloodstream Isolates in Korea: Association With Antifungal Resistance, Mutations in Mismatch Repair Gene (Msh2), and Clinical Outcomes.
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DOI：
10.3389/fmicb.2018.01523
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发表时间：
2018
影响因子：
5.2
通讯作者：
Shin JH
中科院分区：
文献类型：
--
作者：
Byun SA;Won EJ;Kim MN;Lee WG;Lee K;Lee HS;Uh Y;Healey KR;Perlin DS;Choi MJ;Kim SH;Shin JH
据报道，通过多位点序列分型（MLST）分析，来自特定地理区域的光滑念珠菌血流感染（BSI）分离株包含相对较少的主要序列类型（STs）。然而，对主要ST菌株的特征知之甚少。为了解决这个问题，我们在韩国研究了C. glabrata BSI分离株的抗真菌耐药性和错配修复基因（msh2突变）的非同义突变，以及相关的临床特征，并根据MLST基因型比较了结果。我们在2年（2009年和2014年）的时间里评估了韩国7家医院共分离的209株glabrata BSI。对185例念珠菌病的临床特点及预后进行分析。根据MLST， ST7（47.8%）是最常见的类型，其次是ST3 (22.5%)；其余为28种轻微STs（29.7%）。ST7、ST3和其他菌株对氟康唑的耐药率分别为9.0%（9/100）、8.5%（4/47）和4.8%(3/62)，均对两性霉素B和米卡芬菌素敏感。所有ST7分离株都携带msh2的V239L突变，已知具有高易变性，而91.5%的ST3分离株没有携带msh2突变。总的来说，除了9个分离株外，同一株ST的分离株具有相同的msh2突变。68.8%（11/16）的FR分离株和67.4%（130/193）的氟康唑敏感剂量依赖分离株存在msh2突变。ST3和ST7的所有临床特征均无显著差异。然而，两种主要ST （ST3或ST7）菌株引起的光秃念珠菌30天死亡率显著高于其他次要ST菌株引起的念珠菌死亡率（45.1% vs. 25.0%, p < 0.05）。多因素logistic回归分析还显示，两个主要STs （ST3和ST7）是30天死亡率的独立预测因子。该研究首次表明，韩国BSI分离株中ST7和ST3两种STs占主导地位，并且属于两种主要MLST基因型的C. glabrata BSI分离株具有较高的死亡率。此外，大多数msh2突变与MLST基因型一致，与FR无关。
Candida glabrata bloodstream infection (BSI) isolates from a particular geographic area have been reported to comprise a relatively small number of the major sequence types (STs) by multilocus sequence typing (MLST) analysis. Yet little is known about the characteristics of major ST strains of C. glabrata. To address this question in Korea, we investigated antifungal resistance and non-synonymous mutations of the mismatch repair gene (msh2 mutations) in C. glabrata BSI isolates, as well as associated clinical characteristics, and compared the results according to MLST genotype. We assessed a total of 209 C. glabrata BSI isolates from seven hospitals in Korea for 2 years (2009 and 2014). Clinical features of candidemia and their outcomes were analyzed for 185 available cases. According to MLST, ST7 (47.8%) was the most common type, followed by ST3 (22.5%); the remainder represented 28 types of minor STs (29.7%). Fluconazole-resistance (FR) rates for ST7, ST3, and other strains were 9.0% (9/100), 8.5% (4/47), and 4.8% (3/62), respectively, and all were susceptible to amphotericin B and micafungin. All ST7 isolates harbored the V239L mutation in msh2, known to confer hypermutability, while 91.5% of ST3 isolates did not harbor the msh2 mutation. Overall, isolates of the same ST had identical msh2 mutations, with the exception of nine isolates. The msh2 mutations were identified in 68.8% (11/16) of the FR isolates and 67.4% (130/193) of the fluconazole susceptible-dose dependent isolates. There was no significant difference in all clinical characteristics between ST3 and ST7. However, the 30-day mortality of C. glabrata candidemia due to the two major ST (ST3 or ST7) strains was significantly higher than that of candidemia due to other minor ST strains (45.1 vs. 25.0%, p < 0.05). Multivariate logistic regression analysis also showed that two major STs (ST3 and ST7) were independent predictors of 30-day mortality. This study showed for the first time that two STs (ST7 and ST3) were predominant among BSI isolates in Korea, and that C. glabrata BSI isolates belonging to two major MLST genotypes are characterized by higher mortality. In addition, most msh2 mutations align with MLST genotype, irrespective of FR.
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影响因子：
3.2
作者：
Gabaldón T;Carreté L
通讯作者：
Carreté L
影响因子：
16.6
作者：
Healey KR;Zhao Y;Perez WB;Lockhart SR;Sobel JD;Farmakiotis D;Kontoyiannis DP;Sanglard D;Taj-Aldeen SJ;Alexander BD;Jimenez-Ortigosa C;Shor E;Perlin DS
通讯作者：
Perlin DS
影响因子：
11.8
作者：
Chow, Jennifer K.;Golan, Yoav;Hadley, Susan
通讯作者：
Hadley, Susan
影响因子：
3.8
作者：
Hall, WH;Ramachandran, R;Vijayakumar, S
通讯作者：
Vijayakumar, S
影响因子：
2.9
作者：
Ding, Xiurong;Yan, Donghui;Su, Jianrong
通讯作者：
Su, Jianrong