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肝硬化患者肠道内白念珠菌菌株的多位点序列分型。

Multilocus sequence typing for Candida albicans strains from the intestinal tract of patients with cirrhosis.

机构信息

Department of Gastroenterology and Hepatology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.

出版信息

Eur Rev Med Pharmacol Sci. 2018 Sep;22(18):6063-6071. doi: 10.26355/eurrev_201809_15944.

Abstract

OBJECTIVE

Multilocus sequence typing (MLST) was applied to investigate the genetic diversity of Candida albicans in the intestinal tract of cirrhosis patients.

PATIENTS AND METHODS

We used CHROM agar Candida medium to obtain 105 Candida sp. isolates from fecal samples (276 subjects), including 63 isolates from the cirrhosis group (141 subjects) and 42 isolates from the healthy control group (135 subjects).

RESULTS

Among the 105 Candida strains isolated, 60 strains were identified as Candida albicans. Patients with cirrhosis had significantly higher rates of colonization by Candida sp. (44.68% vs. 31.11%, p < 0.05) and C. albicans (27.66% vs. 15.56%, p < 0.05) relative to healthy controls. In the cirrhosis group, the rate of colonization further increased with disease progression and antibiotic treatment (p < 0.01). Sixty C. albicans isolates were analyzed by MLST. Fifty diploid sequence types (DST) were observed, and 26 new DSTs and 3 novel alleles were found. The majority of isolates were distributed among three clades, clade 8 (31.67%), clade 14 (15.00%) and clade 18 (21.67%). Among 39 strains from the cirrhosis group, 16 strains (41.02%) belonged to clade 8, while only 3 strains (14.29%) from healthy group belonged to clade 8 (p < 0.05). In addition, concatenated sequences of the 7 housekeeping gene fragments were analyzed for all the different DSTs in clade 8 to evaluate the loss of heterozygosity (LOH), which indicates C. albicans microvariation in the gut of cirrhosis patients.

CONCLUSIONS

This study suggests that cirrhosis disease progression and antibiotic treatment is associated with increased colonization by Candida sp. and C. albicans. We are the first to provide MLST-based genotype profiles for C. albicans Guizhou China, and to identify clade 8 as the potential main clade of C. albicans colonization in the gut of cirrhosis patients.

摘要

目的

应用多位点序列分型(MLST)方法研究肝硬化患者肠道白色念珠菌的遗传多样性。

方法

我们使用 CHROM 琼脂念珠菌培养基从粪便样本(276 例)中获得 105 株念珠菌属分离株,包括 63 株来自肝硬化组(141 例)和 42 株来自健康对照组(135 例)。

结果

在分离的 105 株念珠菌中,60 株鉴定为白色念珠菌。与健康对照组相比,肝硬化患者的念珠菌属(44.68%比 31.11%,p < 0.05)和白色念珠菌(27.66%比 15.56%,p < 0.05)定植率明显更高。在肝硬化组中,随着疾病进展和抗生素治疗,定植率进一步增加(p < 0.01)。对 60 株白色念珠菌进行 MLST 分析。观察到 50 个二倍体序列型(DST),发现 26 个新的 DST 和 3 个新的等位基因。大多数分离株分布在三个分支中,分支 8(31.67%)、分支 14(15.00%)和分支 18(21.67%)。在肝硬化组的 39 株菌株中,16 株(41.02%)属于分支 8,而健康组只有 3 株(14.29%)属于分支 8(p < 0.05)。此外,还对分支 8 中所有不同 DST 的 7 个管家基因片段的串联序列进行分析,以评估杂合性丢失(LOH),这表明肝硬化患者肠道中白色念珠菌的微变异。

结论

本研究表明,肝硬化疾病进展和抗生素治疗与念珠菌属和白色念珠菌的定植增加有关。我们首次提供了基于 MLST 的中国贵州白色念珠菌基因型图谱,并鉴定分支 8 为肝硬化患者肠道白色念珠菌定植的潜在主要分支。

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