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基于基因组分析对医疗保健相关病原体鲍曼不动杆菌传播和变异的新见解。

New insights into dissemination and variation of the health care-associated pathogen Acinetobacter baumannii from genomic analysis.

作者信息

Wright Meredith S, Haft Daniel H, Harkins Derek M, Perez Federico, Hujer Kristine M, Bajaksouzian Saralee, Benard Michael F, Jacobs Michael R, Bonomo Robert A, Adams Mark D

出版信息

mBio. 2014 Jan 21;5(1):e00963-13. doi: 10.1128/mBio.00963-13.

Abstract

UNLABELLED

Acinetobacter baumannii is a globally important nosocomial pathogen characterized by an increasing incidence of multidrug resistance. Routes of dissemination and gene flow among health care facilities are poorly resolved and are important for understanding the epidemiology of A. baumannii, minimizing disease transmission, and improving patient outcomes. We used whole-genome sequencing to assess diversity and genome dynamics in 49 isolates from one United States hospital system during one year from 2007 to 2008. Core single-nucleotide-variant-based phylogenetic analysis revealed multiple founder strains and multiple independent strains recovered from the same patient yet was insufficient to fully resolve strain relationships, where gene content and insertion sequence patterns added additional discriminatory power. Gene content comparisons illustrated extensive and redundant antibiotic resistance gene carriage and direct evidence of gene transfer, recombination, gene loss, and mutation. Evidence of barriers to gene flow among hospital components was not found, suggesting complex mixing of strains and a large reservoir of A. baumannii strains capable of colonizing patients.

IMPORTANCE

Genome sequencing was used to characterize multidrug-resistant Acinetobacter baumannii strains from one United States hospital system during a 1-year period to better understand how A. baumannii strains that cause infection are related to one another. Extensive variation in gene content was found, even among strains that were very closely related phylogenetically and epidemiologically. Several mechanisms contributed to this diversity, including transfer of mobile genetic elements, mobilization of insertion sequences, insertion sequence-mediated deletions, and genome-wide homologous recombination. Variation in gene content, however, lacked clear spatial or temporal patterns, suggesting a diverse pool of circulating strains with considerable interaction between strains and hospital locations. Widespread genetic variation among strains from the same hospital and even the same patient, particularly involving antibiotic resistance genes, reinforces the need for molecular diagnostic testing and genomic analysis to determine resistance profiles, rather than a reliance primarily on strain typing and antimicrobial resistance phenotypes for epidemiological studies.

摘要

未加标注

鲍曼不动杆菌是一种在全球范围内具有重要意义的医院病原菌,其特征是多重耐药性的发生率不断上升。医疗机构之间的传播途径和基因流动情况尚未完全明确,而这对于了解鲍曼不动杆菌的流行病学、最大限度减少疾病传播以及改善患者治疗结果至关重要。我们使用全基因组测序技术,对2007年至2008年期间从美国一家医院系统分离出的49株菌株进行了多样性和基因组动态评估。基于核心单核苷酸变异的系统发育分析揭示了多个始祖菌株以及从同一患者体内分离出的多个独立菌株,但这不足以完全解析菌株之间的关系,而基因含量和插入序列模式则提供了额外的鉴别力。基因含量比较显示出广泛且冗余的抗生素耐药基因携带情况以及基因转移、重组、基因丢失和突变的直接证据。未发现医院各部门之间存在基因流动障碍的证据,这表明菌株存在复杂的混合情况,且有大量能够定植于患者的鲍曼不动杆菌菌株库。

重要性

在为期1年的时间里,我们利用基因组测序技术对来自美国一家医院系统的多重耐药鲍曼不动杆菌菌株进行了特征分析,以便更好地了解引起感染的鲍曼不动杆菌菌株之间的相互关系。我们发现,即使在系统发育和流行病学上密切相关的菌株之间,基因含量也存在广泛差异。多种机制促成了这种多样性,包括移动遗传元件的转移、插入序列的移动、插入序列介导的缺失以及全基因组同源重组。然而,基因含量的变异缺乏明确的空间或时间模式,这表明存在一个多样化的循环菌株库,菌株与医院地点之间存在大量相互作用。同一医院甚至同一患者的菌株之间存在广泛的基因变异,尤其是涉及抗生素耐药基因的变异,这进一步凸显了进行分子诊断检测和基因组分析以确定耐药谱的必要性,而不是主要依赖菌株分型和抗菌药物耐药表型进行流行病学研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/02a5/3903280/41ca95585c6a/mbo0061317050001.jpg

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