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不同的表型和基因组特征是克隆谱系不同致病潜力的基础。

Distinct Phenotypic and Genomic Signatures Underlie Contrasting Pathogenic Potential of Clonal Lineages.

作者信息

Espadinha Diana, Sobral Rita G, Mendes Catarina Inês, Méric Guillaume, Sheppard Samuel K, Carriço João A, de Lencastre Hermínia, Miragaia Maria

机构信息

Laboratory of Bacterial Evolution and Molecular Epidemiology, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.

Laboratory of Molecular Genetics, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Oeiras, Portugal.

出版信息

Front Microbiol. 2019 Aug 27;10:1971. doi: 10.3389/fmicb.2019.01971. eCollection 2019.

Abstract

is a common skin commensal that has emerged as a pathogen in hospitals, mainly related to medical devices-associated infections. Noteworthy, infection rates by have the tendency to rise steeply in next decades together with medical devices use and immunocompromized population growth. population structure includes two major clonal lineages (A/C and B) that present contrasting pathogenic potentials. To address this distinction and explore the basis of increased pathogenicity of A/C lineage, we performed a detailed comparative analysis using phylogenetic and integrated pangenome-wide-association study (panGWAS) approaches and compared the lineages's phenotypes in conditions mimicking carriage and infection. Each lineage had distinct phenotypic signatures in skin and infection conditions and differed in genomic content. Combination of phenotypic and genotypic data revealed that both lineages were well adapted to skin environmental cues. However, they appear to occupy different skin niches, perform distinct biological functions in the skin and use different mechanisms to complete the same function: lineage B strains showed evidence of specialization to survival in microaerobic and lipid rich environment, characteristic of hair follicle and sebaceous glands; lineage A/C strains showed evidence for adaption to diverse osmotic and pH conditions, potentially allowing them to occupy a broader and more superficial skin niche. In infection conditions, A/C strains had an advantage, having the potential to bind blood-associated host matrix proteins, form biofilms at blood pH, resist antibiotics and macrophage acidity and to produce proteases. These features were observed to be rare in the lineage B strains. PanGWAS analysis produced a catalog of putative virulence factors and identified an epidemiological molecular marker for the more pathogenic lineage. The prevalence of A/C lineage in infection is probably related to a higher metabolic and genomic versatility that allows rapid adaptation during transition from a commensal to a pathogenic lifestyle. The putative virulence and phenotypic factors associated to A/C lineage constitute a reliable framework for future studies on pathogenesis and the finding of an epidemiological marker for the more pathogenic lineage is an asset for the management of infections.

摘要

是一种常见的皮肤共生菌,已成为医院中的病原体,主要与医疗器械相关感染有关。值得注意的是,随着医疗器械的使用和免疫功能低下人群的增加,由其引起的感染率在未来几十年有急剧上升的趋势。其种群结构包括两个主要的克隆谱系(A/C和B),它们具有截然不同的致病潜力。为了阐明这种差异并探究A/C谱系致病性增加的基础,我们使用系统发育和整合全基因组关联研究(panGWAS)方法进行了详细的比较分析,并在模拟携带和感染的条件下比较了这两个谱系的表型。每个谱系在皮肤和感染条件下都有独特的表型特征,并且基因组内容也有所不同。表型和基因型数据的结合表明,两个谱系都能很好地适应皮肤环境线索。然而,它们似乎占据不同的皮肤生态位,在皮肤中执行不同的生物学功能,并使用不同的机制来完成相同的功能:B谱系菌株显示出在微需氧和富含脂质的环境(毛囊和皮脂腺的特征)中生存的特化证据;A/C谱系菌株显示出适应多种渗透压和pH条件的证据,这可能使它们能够占据更广泛、更浅表的皮肤生态位。在感染条件下,A/C菌株具有优势,它们有可能结合与血液相关的宿主基质蛋白,在血液pH值下形成生物膜,抵抗抗生素和巨噬细胞酸性,并产生蛋白酶。这些特征在B谱系菌株中很少见。PanGWAS分析产生了一份假定的毒力因子目录,并为致病性更强的谱系鉴定了一个流行病学分子标记。A/C谱系在感染中的流行可能与更高的代谢和基因组多功能性有关,这使得它们在从共生生活方式转变为致病生活方式的过程中能够快速适应。与A/C谱系相关的假定毒力和表型因子构成了未来关于其发病机制研究的可靠框架,而发现致病性更强的谱系的流行病学标记对于其感染的管理是一项资产。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/003a/6719527/b05bda54094e/fmicb-10-01971-g001.jpg

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