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产酸克氏杆菌的种群结构、抗生素耐药性和尿路致病性。

Population Structure, Antibiotic Resistance, and Uropathogenicity of Klebsiella variicola.

机构信息

The Edison Family Center for Genome Sciences and Systems Biology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA.

Department of Pathology and Immunology, Washington University in St. Louis School of Medicine, St. Louis, Missouri, USA.

出版信息

mBio. 2018 Dec 18;9(6):e02481-18. doi: 10.1128/mBio.02481-18.

Abstract

is a member of the genus and often misidentified as or The importance of human infections has been known; however, a dearth of relative knowledge exists for Despite its growing clinical importance, comprehensive analyses of population structure and mechanistic investigations of virulence factors and antibiotic resistance genes have not yet been performed. To address this, we utilized , , and methods to study a cohort of isolates and genomes. We found that the population structure has two distant lineages composed of two and 143 genomes, respectively. Ten of 145 genomes harbored carbapenem resistance genes, and 6/145 contained complete virulence operons. While the β-lactam and quinolone antibiotic resistance genes were generally conserved within our institutional cohort, unexpectedly 11 isolates were nonresistant to the β-lactam ampicillin and only one isolate was nonsusceptible to the quinolone ciprofloxacin. isolates have variation in ability to cause urinary tract infections in a newly developed murine model, but importantly a strain had statistically significant higher bladder CFU than the model uropathogenic strain TOP52. Type 1 pilus and genomic identification of altered operon structure were associated with differences in bladder CFU for the tested strains. Nine newly reported types of pilus genes were discovered in the pan-genome, including the first identified P-pilus in spp. Infections caused by antibiotic-resistant bacterial pathogens are a growing public health threat. Understanding of pathogen relatedness and biology is imperative for tracking outbreaks and developing therapeutics. Here, we detail the phylogenetic structure of 145 genomes from different continents. Our results have important clinical ramifications as high-risk antibiotic resistance genes are present in genomes from a variety of geographic locations and as we demonstrate that clinical isolates can establish higher bladder titers than Differential presence of these pilus genes in isolates may indicate adaption for specific environmental niches. Therefore, due to the potential of multidrug resistance and pathogenic efficacy, identification of and to a species level should be performed to optimally improve patient outcomes during infection. This work provides a foundation for our improved understanding of biology and pathogenesis.

摘要

是 属的成员,常被误认为 或 。 人类感染的重要性是已知的;然而,对于 相对的知识却很少。尽管其临床重要性日益增加,但尚未对 种群结构进行全面分析,也未对毒力因子和抗生素耐药基因进行机制研究。为了解决这个问题,我们利用 、 和 方法来研究一组 分离株和基因组。我们发现, 种群结构由两个远缘谱系组成,分别由两个和 143 个基因组组成。在 145 个 基因组中,有 10 个携带碳青霉烯类抗生素耐药基因,有 6 个/145 个含有完整的毒力操纵子。虽然我们机构队列中的β-内酰胺 和喹诺酮 抗生素耐药基因通常是保守的,但出乎意料的是,有 11 个分离株对β-内酰胺氨苄西林不耐药,只有一个分离株对喹诺酮环丙沙星不敏感。 在新开发的小鼠模型中,对尿路感染的致病能力存在差异,但重要的是,一种菌株的膀胱 CFU 明显高于模型尿路致病性 菌株 TOP52。1 型菌毛和 操纵子结构的基因组鉴定与测试菌株膀胱 CFU 的差异有关。在 泛基因组中发现了 9 种新报告的菌毛基因类型,包括在 spp 中首次发现的 P-菌毛。由抗生素耐药细菌病原体引起的感染是一个日益严重的公共卫生威胁。了解病原体的亲缘关系和生物学特性对于跟踪疫情和开发治疗方法至关重要。在这里,我们详细描述了来自不同大陆的 145 个 基因组的系统发育结构。我们的研究结果具有重要的临床意义,因为来自不同地理位置的 基因组中存在高风险的抗生素耐药基因,并且我们证明了 临床分离株可以比 建立更高的膀胱滴度。 分离株中这些菌毛基因的不同存在可能表明它们适应了特定的环境小生境。因此,由于具有多药耐药性和致病性的潜力,应将 鉴定到种水平,以在感染期间优化患者的治疗效果。这项工作为我们更好地理解 生物学和发病机制提供了基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0da6/6299229/10151ca4cdf6/mbo0061842370001.jpg

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