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比较基因组学和表型分析对产 SPM-1 金属β-内酰胺酶铜绿假单胞菌的特性研究。

Characterization of a SPM-1 metallo-beta-lactamase-producing Pseudomonas aeruginosa by comparative genomics and phenotypic analysis.

机构信息

Programa de Computação Científica, Fundação Oswaldo Cruz, Rio de Janeiro, 21040-360, Brazil.

Centro de Desenvolvimento Tecnológico em Saúde, Fundação Oswaldo Cruz, Rio de Janeiro, 21040-361, Brazil.

出版信息

Sci Rep. 2020 Aug 6;10(1):13192. doi: 10.1038/s41598-020-69944-6.

DOI:10.1038/s41598-020-69944-6
PMID:32764694
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7413544/
Abstract

Pseudomonas aeruginosa is one of the most common pathogens related to healthcare-associated infections. The Brazilian isolate, named CCBH4851, is a multidrug-resistant clone belonging to the sequence type 277. The antimicrobial resistance mechanisms of the CCBH4851 strain are associated with the presence of the bla[Formula: see text] gene, encoding a metallo-beta-lactamase, in combination with other exogenously acquired genes. Whole-genome sequencing studies focusing on emerging pathogens are essential to identify key features of their physiology that may lead to the identification of new targets for therapy. Using both Illumina and PacBio sequencing data, we obtained a single contig representing the CCBH4851 genome with annotated features that were consistent with data reported for the species. However, comparative analysis with other Pseudomonas aeruginosa strains revealed genomic differences regarding virulence factors and regulatory proteins. In addition, we performed phenotypic assays that revealed CCBH4851 is impaired in bacterial motilities and biofilm formation. On the other hand, CCBH4851 genome contained acquired genomic islands that carry transcriptional factors, virulence and antimicrobial resistance-related genes. Presence of single nucleotide polymorphisms in the core genome, mainly those located in resistance-associated genes, suggests that these mutations may also influence the multidrug-resistant behavior of CCBH4851. Overall, characterization of Pseudomonas aeruginosa CCBH4851 complete genome revealed the presence of features that strongly relates to the virulence and antibiotic resistance profile of this important infectious agent.

摘要

铜绿假单胞菌是与医疗保健相关感染有关的最常见病原体之一。巴西分离株 CCBH4851 是一种多药耐药克隆，属于序列类型 277。CCBH4851 株的抗菌药物耐药机制与 bla[Formula: see text]基因的存在有关，该基因编码一种金属β-内酰胺酶，与其他外源性获得的基因一起。针对新兴病原体的全基因组测序研究对于识别其生理学的关键特征至关重要，这些特征可能导致发现新的治疗靶点。使用 Illumina 和 PacBio 测序数据，我们获得了一个代表 CCBH4851 基因组的单个连续体，其注释特征与该物种报告的数据一致。然而，与其他铜绿假单胞菌菌株的比较分析显示，在毒力因子和调节蛋白方面存在基因组差异。此外，我们进行了表型测定，结果显示 CCBH4851 在细菌运动性和生物膜形成方面受损。另一方面，CCBH4851 基因组包含携带转录因子、毒力和抗菌药物耐药相关基因的获得性基因组岛。核心基因组中单核苷酸多态性的存在，主要是那些位于耐药相关基因中的多态性，表明这些突变也可能影响 CCBH4851 的多药耐药行为。总的来说，对铜绿假单胞菌 CCBH4851 全基因组的特征分析揭示了与该重要感染因子的毒力和抗生素耐药谱密切相关的特征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a6/7413544/2459015039e5/41598_2020_69944_Fig7_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a6/7413544/690f62f3e540/41598_2020_69944_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a6/7413544/79a6da036846/41598_2020_69944_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a6/7413544/2459015039e5/41598_2020_69944_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a6/7413544/54992a1f1b42/41598_2020_69944_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a6/7413544/a7d637408811/41598_2020_69944_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a6/7413544/090dbad2b462/41598_2020_69944_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a6/7413544/f497206cc3ad/41598_2020_69944_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a6/7413544/690f62f3e540/41598_2020_69944_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a6/7413544/79a6da036846/41598_2020_69944_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d6a6/7413544/2459015039e5/41598_2020_69944_Fig7_HTML.jpg

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