应用基质辅助激光解吸电离飞行时间质谱研究白色念珠菌血流感染的血清多肽指纹图谱

Analysis of serum peptides in Candida albicans bloodstream infection based on MALDI-TOF MS

目的应用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF MS)分析白色念珠菌所致血流感染的血清多肽指纹图谱,寻找差异多肽峰并建立相应的诊断模型。方法建立ICR小鼠白色念珠菌血流感染模型,收集血清标本,经弱阳离子磁珠纯化,MALDI-TOF MS检测及BioExplorer软件分析白色念珠菌感染与正常对照组的血清多肽指纹图谱,同时分析大肠埃希菌感染组、金黄色葡萄球菌感染组和白色念珠菌感染组的血清多肽指纹图谱。结果比较白色念珠菌感染组和正常对照组共得到135个多肽峰,其中表达上调的多肽有5个,表达下调的多肽有6个,表达呈先上调后下调的多肽有7个,组合m/z 1610.9、1742.3、2666.4、2778.0、3345.1、4528.8这6个峰建立诊断模型,该模型区分白色念珠菌感染的正确率为80.0%。综合比较大肠埃希菌感染组、金葡菌感染组和白色念珠菌感染组的血清多肽指纹图谱发现,有5个多肽峰在感染组中共同出现,分别为m/z 1513.8、2910.8、3538.1、3884.9和5007.3。结论利用MALDI-TOF MS可有效区分白色念珠菌感染和正常血清的多肽峰,同时感染中共同出现的多肽峰有望成为辅助诊断血流感染的标志物,通过建立相应的诊断模型能早期辅助诊断真菌性血流感染,为临床合理用药及标志物寻找提供依据。

Objective To analyze the fingerprints of serum peptides in bloodstream infection induced by Candida albicans（C. albicans）, with matrix assisted laser desorption ionization time-of-flight mass spectrometry（MALDI-TOF MS）, and establish the corresponding diagnostic model. Methods To establish ICR mice model of C. albicans bloodstream infection, and collect the serum samples which were purified by weak cation exchange beads. The serum peptide finger printing was recognized by MALDITOF MS, and Bio Explorer software was used for analysis between infection group and normal control group. Furthermore, the peptide fingerprints were analyzed between C. albicans infection group, Escherichia coli（E. coli） infection group and Staphylococcus aureus（S. aureus） infection group. Results Comparison between C. albicans infection group and normal control group, there were 135 polypeptide peaks, of which 5 polypeptides up-regulated, 6 down-regulated and 7 up-regulated first and down-regulated afterwards. The diagnostic model was established by combination of 6 peaks（i.e. m/z 1610.9, 1742.3, 2666.4, 2778.0, 3345.1 and 4528.8）, which possessed an accurate rate of 80.0% in diagnosis of C. albicans infection. It was found by comprehensive comparison between C. albicans, E. coli and S. aureus infection groups that there were 5 polypeptides expressed collectively, i.e. m/z1513.8, 2910.8, 3538.1, 3884.9 and 5007.3. Conclusions MALDI-TOF MS can be used to distinguish the C. albicans infection and normal polypeptide peaks. The collective polypeptides expressed in the infection groups can be further used to diagnose the infection. Establishment of corresponding diagnostic models may be helpful for early diagnosis of fungal bloodstream infection and provide a basis for reasonable clinical medication.