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可变阿波菲孢霉:基因组草图序列以及与其他医学重要毛霉目真菌预测毒力决定因素的比较

Apophysomyces variabilis: draft genome sequence and comparison of predictive virulence determinants with other medically important Mucorales.

作者信息

Prakash Hariprasath, Rudramurthy Shivaprakash Mandya, Gandham Prasad S, Ghosh Anup Kumar, Kumar Milner M, Badapanda Chandan, Chakrabarti Arunaloke

机构信息

Department of Medical Microbiology, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.

Microbial Type Culture Collection and Gene Bank (MTCC), CSIR-Institute of Microbial Technology, Chandigarh, 160036, India.

出版信息

BMC Genomics. 2017 Sep 18;18(1):736. doi: 10.1186/s12864-017-4136-1.

Abstract

BACKGROUND

Apophysomyces species are prevalent in tropical countries and A. variabilis is the second most frequent agent causing mucormycosis in India. Among Apophysomyces species, A. elegans, A. trapeziformis and A. variabilis are commonly incriminated in human infections. The genome sequences of A. elegans and A. trapeziformis are available in public database, but not A. variabilis. We, therefore, performed the whole genome sequence of A. variabilis to explore its genomic structure and possible genes determining the virulence of the organism.

RESULTS

The whole genome of A. variabilis NCCPF 102052 was sequenced and the genomic structure of A. variabilis was compared with already available genome structures of A. elegans, A. trapeziformis and other medically important Mucorales. The total size of genome assembly of A. variabilis was 39.38 Mb with 12,764 protein-coding genes. The transposable elements (TEs) were low in Apophysomyces genome and the retrotransposon Ty3-gypsy was the common TE. Phylogenetically, Apophysomyces species were grouped closely with Phycomyces blakesleeanus. OrthoMCL analysis revealed 3025 orthologues proteins, which were common in those three pathogenic Apophysomyces species. Expansion of multiple gene families/duplication was observed in Apophysomyces genomes. Approximately 6% of Apophysomyces genes were predicted to be associated with virulence on PHIbase analysis. The virulence determinants included the protein families of CotH proteins (invasins), proteases, iron utilisation pathways, siderophores and signal transduction pathways. Serine proteases were the major group of proteases found in all Apophysomyces genomes. The carbohydrate active enzymes (CAZymes) constitute the majority of the secretory proteins.

CONCLUSION

The present study is the maiden attempt to sequence and analyze the genomic structure of A. variabilis. Together with available genome sequence of A. elegans and A. trapeziformis, the study helped to indicate the possible virulence determinants of pathogenic Apophysomyces species. The presence of unique CAZymes in cell wall might be exploited in future for antifungal drug development.

摘要

背景

附肢霉属在热带国家普遍存在,而变异附肢霉是印度引起毛霉病的第二常见病原体。在附肢霉属中,雅致附肢霉、梯形附肢霉和变异附肢霉通常被认为是人类感染的病原体。雅致附肢霉和梯形附肢霉的基因组序列可在公共数据库中获取,但变异附肢霉的没有。因此,我们对变异附肢霉进行了全基因组测序,以探索其基因组结构和可能决定该生物体毒力的基因。

结果

对变异附肢霉NCCPF 102052的全基因组进行了测序,并将变异附肢霉的基因组结构与已有的雅致附肢霉、梯形附肢霉及其他医学上重要的毛霉目的基因组结构进行了比较。变异附肢霉基因组组装的总大小为39.38 Mb,有12764个蛋白质编码基因。附肢霉基因组中的转座元件(TEs)较少,反转录转座子Ty3-gypsy是常见的TE。在系统发育上,附肢霉属物种与布氏毛霉紧密聚类。直系同源聚类分析(OrthoMCL)显示,这三种致病性附肢霉属物种共有3025个直系同源蛋白。在附肢霉基因组中观察到多个基因家族的扩增/重复。在PHIbase分析中,约6%的附肢霉基因被预测与毒力相关。毒力决定因素包括CotH蛋白(侵袭素)、蛋白酶、铁利用途径、铁载体和信号转导途径等蛋白家族。丝氨酸蛋白酶是在所有附肢霉基因组中发现的主要蛋白酶类群。碳水化合物活性酶(CAZymes)构成了分泌蛋白的大部分。

结论

本研究是首次对变异附肢霉的基因组进行测序和分析。结合已有的雅致附肢霉和梯形附肢霉的基因组序列,该研究有助于揭示致病性附肢霉属物种可能的毒力决定因素。细胞壁中独特的CAZymes的存在未来可能会被用于抗真菌药物的开发。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7a12/5604411/44bc867ffdf0/12864_2017_4136_Fig1_HTML.jpg

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