MSH2 Gene Point Mutations Are Not Antifungal Resistance Markers in Candida glabrata
MSH2 Gene Point Mutations Are Not Antifungal Resistance Markers in Candida glabrata
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DOI：
10.1128/aac.01876-18
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发表时间：
2019-01-01
影响因子：
4.9
通讯作者：
Guinea, Jesus
中科院分区：
文献类型：
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作者：
Angeles Bordallo-Cardona, Maria;Agnelli, Caroline;Guinea, Jesus
光滑念珠菌抗真菌耐药率高可能是由于MSH 2基因的改变。目的研究124例侵袭性念珠菌MSH 2基因的序列。光滑念珠菌分离株引起的念珠菌血症事件（n = 81），随后的念珠菌血症事件（n = 9），心内膜炎（n = 2），并在体外产生的棘白菌素耐药菌株（n = 32），并评估其与基因型，获得抗真菌药在体内和体外，和患者预后的关系。MSH 2基因进行测序，并使用6个微卫星标记和基于6个管家基因的多位点序列分型（MLST）的分离株进行基因分型。根据EUCAST，引起念珠菌血症的分离株（n = 90）对棘白菌素敏感，其中4株对氟康唑耐药（MIC = 64 mg/L）。从心脏瓣膜获得的一种分离株对米卡芬净和阿尼芬净耐药（MIC分别为2 mg/L和1 mg/L）。MSH 2基因突变存在于44.4%的事件分离株中，最常见的是V239 L。MSH 2突变的存在与体外或体内抗真菌药耐药性无关。微卫星和MLST分别揭示了27种基因型和17种序列类型。氟康唑耐药菌株无关。大多数MSH 2突变发现在集群分离株;相反，一些突变被发现在一个以上的基因型。在感染野生型MSH 2基因分离株和任何点突变的分离株的患者之间没有发现临床差异，包括既往抗真菌药物的使用。C.引起念珠菌血症的光滑念珠菌分离株与特定基因型、抗真菌药耐药性的促进或临床结果无关。
The high rates of antifungal resistance in Candida glabrata may be facilitated by the presence of alterations in the MSH2 gene. We aimed to study the sequence of the MSH2 gene in 124 invasive C. glabrata isolates causing incident episodes of candidemia (n = 81), subsequent candidemia episodes (n = 9), endocarditis (n = 2), and in vitro-generated echinocandin-resistant isolates (n = 32) and assessed its relationship with genotypes, acquisition of antifungal resistance in vivo and in vitro, and patient prognosis. The MSH2 gene was sequenced, and isolates were genotyped using six microsatellite markers and multilocus sequence typing (MLST) based on six housekeeping genes. According to EUCAST, isolates causing candidemia (n = 90) were echinocandin susceptible, and four of them were fluconazole resistant (MIC = 64 mg/liter). One isolate obtained from a heart valve was resistant to micafungin and anidulafungin (MICs, 2 mg/liter and 1 mg/liter, respectively). MSH2 gene mutations were present in 44.4% of the incident isolates, the most common being V239L. The presence of MSH2 mutations was not correlated with in vitro or in vivo antifungal resistance. Microsatellite and MLST revealed 27 genotypes and 17 sequence types, respectively. Fluconazole-resistant isolates were unrelated. Most MSH2 mutations were found in cluster isolates; conversely, some mutations were found in more than one genotype. No clinical differences, including previous antifungal use, were found between patients infected by wild-type MSH2 gene isolates and isolates with any point mutation. The presence of MSH2 gene mutations in C. glabrata isolates causing candidemia is not correlated with specific genotypes, the promotion of antifungal resistance, or the clinical outcome.