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首页> 外文期刊>Microbial Pathogenesis >Identification of genomic loci associated with genotypic and phenotypic variation among Pseudomonas aeruginosa clinical isolates from pneumonia
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Identification of genomic loci associated with genotypic and phenotypic variation among Pseudomonas aeruginosa clinical isolates from pneumonia

机译：抗肺炎铜绿假单胞菌临床分离株基因型和表型变异相关基因组靶的鉴定

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In this work, a genotype-phenotype survey of a highly diversified Pseudomonas aeruginosa collection was conducted, aiming to detail pathogen-associated scenarios that clinicians face nowadays. Genetic relation based on RAPD-PCR of 705 isolates, retrieved from 424 patients and several clinical contexts, reported an almost isolate-specific molecular-pattern. Pneumonia-associated isolates HB13 and HB15, clustered in the same RAPD-PCR group, were selected to evaluate the genomic background underlying their contrasting antibiotic resistance and virulence. The HB13 genome harbors antibiotic-inactivating enzymes-coding genes (e.g. aac(3)-Ia, arr, bla(VIM)(-2)) and single-nucleotide variations (SNVs) in antibiotic targets, likely accounting for its pan-resistance, whereas HB15 susceptibility correlated to predicted dysfunctional alleles. Isolate HB13 showed the unprecedented rhl-cluster absence and variations in other pathogen competitiveness contributors. Conversely, HB15 genome comprises exoenzyme-coding genes and SNVs linked to increased virulence. Secretome analysis identified signatures features with unknown function as potential novel pathogenic (e.g. a MATE-protein in HB13, a protease in HB15) and antibiotic resistance (a HlyD-like secretion protein in HB13) determinants. Detection of active prophages, proteases (including protease IV and alkaline metalloproteinase), a porin and a peptidase in HB15 highlights the secreted arsenal likely essential for its virulent behavior. The presented phenotype-genome association will contribute to the current knowledge on Pseudomonas aeruginosa pathogenomics.
机译：在这项工作中，进行了高度多样化的假单胞菌铜绿假单胞菌的基因型 - 表型调查，旨在详述临床医生现在面对的病原体相关方案。基于RAPD-PCR为705分离物的遗传关系，从424名患者中检索和几种临床环境，报告了几乎孤立特异性的分子模式。选择在相同的RAPD-PCR组中聚集的肺炎相关分离物HB13和HB15，以评估其对比抗生素抗性和毒力的基因组背景。 HB13基因组患者抗生素灭活酶编码基因（例如AAC（3），ARR，BLA（ - 2））和抗生素靶标中的单核苷酸变化（SNV），可能会占其泛抗性，而HB15易感性与预测功能障碍等位基因相关。孤立HB13显示出前所未有的RHL簇缺席和其他病原体竞争力贡献者的变化。相反，HB15基因组包括脱酶编码基因和与增加的毒力增加的SNV。沉淀分析将具有未知功能的签名特征是潜在的新致病（例如HB13中的Mate-蛋白，Hb15中的蛋白酶）和抗生素抗性（HB13中的Hyd样分泌蛋白）的决定簇。检测活性血管，蛋白酶（包括蛋白酶IV和碱金属蛋白酶），孔隙酶和HB15中的肽酶突出了可能对其毒力行为至关重要的分泌的武器。呈现的表型基因组协会将有助于目前关于铜绿假单胞菌遗传因子的知识。

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