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系统发育群特异性变异塑造了铜绿假单胞菌基因组可塑性区域中抗菌药物耐药基因和防御系统的聚类。

Phylogroup-specific variation shapes the clustering of antimicrobial resistance genes and defence systems across regions of genome plasticity in Pseudomonas aeruginosa.

机构信息

Antibiotic Resistance Group, Max-Planck Institute for Evolutionary Biology, Plön, Germany; Evolutionary Ecology and Genetics, University of Kiel, Kiel, Germany.

Evolutionary Ecology and Genetics, University of Kiel, Kiel, Germany; Department of Infectious Diseases and Microbiology, University of Lübeck, Lübeck, Germany.

出版信息

EBioMedicine. 2023 Apr;90:104532. doi: 10.1016/j.ebiom.2023.104532. Epub 2023 Mar 21.

Abstract

BACKGROUND

Pseudomonas aeruginosa is an opportunistic pathogen consisting of three phylogroups (hereafter named A, B, and C). Here, we assessed phylogroup-specific evolutionary dynamics across available and also new P. aeruginosa genomes.

METHODS

In this genomic analysis, we first generated new genome assemblies for 18 strains of the major P. aeruginosa clone type (mPact) panel, comprising a phylogenetically diverse collection of clinical and environmental isolates for this species. Thereafter, we combined these new genomes with 1991 publicly available P. aeruginosa genomes for a phylogenomic and comparative analysis. We specifically explored to what extent antimicrobial resistance (AMR) genes, defence systems, and virulence genes vary in their distribution across regions of genome plasticity (RGPs) and "masked" (RGP-free) genomes, and to what extent this variation differs among the phylogroups.

FINDINGS

We found that members of phylogroup B possess larger genomes, contribute a comparatively larger number of pangenome families, and show lower abundance of CRISPR-Cas systems. Furthermore, AMR and defence systems are pervasive in RGPs and integrative and conjugative/mobilizable elements (ICEs/IMEs) from phylogroups A and B, and the abundance of these cargo genes is often significantly correlated. Moreover, inter- and intra-phylogroup interactions occur at the accessory genome level, suggesting frequent recombination events. Finally, we provide here the mPact panel of diverse P. aeruginosa strains that may serve as a valuable reference for functional analyses.

INTERPRETATION

Altogether, our results highlight distinct pangenome characteristics of the P. aeruginosa phylogroups, which are possibly influenced by variation in the abundance of CRISPR-Cas systems and are shaped by the differential distribution of other defence systems and AMR genes.

FUNDING

German Science Foundation, Max-Planck Society, Leibniz ScienceCampus Evolutionary Medicine of the Lung, BMBF program Medical Infection Genomics, Kiel Life Science Postdoc Award.

摘要

背景

铜绿假单胞菌是一种机会性病原体,由三个系统发育群(以下分别命名为 A、B 和 C)组成。在此,我们评估了现有和新的铜绿假单胞菌基因组中特定系统发育群的进化动态。

方法

在这项基因组分析中,我们首先为主要铜绿假单胞菌克隆型(mPact)面板的 18 个菌株生成新的基因组组装,该面板包含该物种的具有系统发育多样性的临床和环境分离株的集合。此后,我们将这些新基因组与 1991 个公开可用的铜绿假单胞菌基因组相结合,进行了系统发育和比较分析。我们特别探讨了抗微生物药物耐药性(AMR)基因、防御系统和毒力基因在基因组可塑性区域(RGP)和“掩蔽”(无 RGP)基因组中的分布程度,以及这种变异在不同系统发育群之间的差异。

发现

我们发现,B 系统发育群的成员具有较大的基因组,贡献了相对较多的泛基因组家族,并且 CRISPR-Cas 系统的丰度较低。此外,AMR 和防御系统在 A 和 B 系统发育群的 RGP 中普遍存在,整合和共轭/可移动元件(ICE/IME)中也存在,这些载体基因的丰度通常显著相关。此外,种间和种内相互作用发生在辅助基因组水平上,表明经常发生重组事件。最后,我们在此提供了多样化的铜绿假单胞菌菌株的 mPact 面板,可作为功能分析的有价值的参考。

解释

总的来说,我们的结果突出了铜绿假单胞菌系统发育群的独特泛基因组特征,这些特征可能受到 CRISPR-Cas 系统丰度的变化影响,并受其他防御系统和 AMR 基因的差异分布所塑造。

资助

德国科学基金会、马克斯·普朗克学会、莱布尼茨肺部进化医学科学园区、BMBF 计划医学感染基因组学、基尔生命科学博士后奖。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2f3b/10053402/54645e969ea3/gr1.jpg

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