Time Series Genomics of Pseudomonas aeruginosa Reveals the Emergence of a Hypermutator Phenotype and Within-Host Evolution in Clinical Inpatients.
Time Series Genomics of Pseudomonas aeruginosa Reveals the Emergence of a Hypermutator Phenotype and Within-Host Evolution in Clinical Inpatients.
复制标题
铜绿假单胞菌的时间序列基因组学揭示了临床住院患者中超突变表型的出现和宿主内进化
DOI：
10.1128/spectrum.00057-22
复制
发表时间：
2022-08-31
影响因子：
3.7
通讯作者：
Ni, Ming
中科院分区：
文献类型：
--
作者：
Liu, Hongjie;Yang, Lang;Chen, Qichao;Song, Hongbin;Bo, Xiaochen;Guo, Jingyu;Li, Peng;Ni, Ming
关键词：
铜绿假单胞菌是一种常见的条件致病菌，是医院感染的主要病原菌之一。许多先前的研究已经报道了铜绿假单胞菌感染的医院传播和流行病学。然而，关于铜绿假单胞菌定植和感染在卫生保健环境中的动态的纵向研究是有限的。我们从长期入住重症监护室（ICU）的老年患者中获得纵向样本（约4至19个月）。铜绿假单胞菌分离自7名患者的71份样本，并通过全基因组测序进行表征。铜绿假单胞菌分离株被分配到10个克隆复合体，在两名患者的连续痰液样本中观察到主要克隆的转换。通过比较克隆内基因组差异，我们确定了两个克隆，具有显着较高的单核苷酸多态性和变异的同聚序列比其他克隆，表明hypermutator表型。这些超变子克隆与MutL蛋白中的突变T147 I/G521 S和P27 L相关，它们的突变率估计分别为每年每个核苷酸3.20 × 10−5和6.59 × 10−5。我们还确定了24个反复突变的基因，表现出在两个或两个以上的克隆内的多样性。值得注意的是，在4个克隆中观察到一个复发突变，FptA中的S698 F。这些发现表明，铜绿假单胞菌的趋同微进化和适应发生在长期ICU患者中。铜绿假单胞菌是引起医院感染的主要机会致病菌。不适当的经验性治疗可导致住院时间延长和死亡率增加。在我们对住院患者的铜绿假单胞菌分离株的连续研究中，观察到高度的宿主内多样性，包括克隆的转换和超变表型的出现。反复突变的基因也表明，铜绿假单胞菌的趋同微进化和适应发生在住院患者中，基因组多样性与多重耐药谱的差异有关。总之，我们的研究结果强调了纵向监测医院铜绿假单胞菌克隆的重要性。
Pseudomonas aeruginosa, a common opportunistic pathogen, is one of the leading etiological agents of nosocomial infections. Many previous studies have reported the nosocomial transmission and epidemiology of P. aeruginosa infections. However, longitudinal studies regarding the dynamics of P. aeruginosa colonization and infection in health care settings are limited. We obtained longitudinal samples from aged patients with prolonged intensive care unit (ICU) stays (~4 to 19 months). P. aeruginosa was isolated from 71 samples obtained from seven patients and characterized by whole-genome sequencing. The P. aeruginosa isolates were assigned to 10 clonal complexes, and turnover of main clones was observed in sequential sputum samples from two patients. By comparing intraclonal genomic diversities, we identified two clones that had significantly higher numbers of single nucleotide polymorphisms and variations in homopolymeric sequences than the other clones, indicating a hypermutator phenotype. These hypermutator clones were associated with mutations T147I/G521S and P27L in the MutL protein, and their mutation rates were estimated to be 3.20 × 10−5 and 6.59 × 10−5 per year per nucleotide, respectively. We also identified 24 recurrently mutated genes that exhibited intraclonal diversity in two or more clones. Notably, one recurrent mutation, S698F in FptA, was observed in four clones. These findings suggest that convergent microevolution and adaption of P. aeruginosa occur in long-term ICU patients. IMPORTANCE Pseudomonas aeruginosa is a predominant opportunistic pathogen that causes nosocomial infections. Inappropriate empirical therapy can lead to prolonged hospital stays and increased mortality. In our study of sequential P. aeruginosa isolates from inpatients, high intrahost diversity was observed, including switching of clones and the emergence of a hypermutator phenotype. Recurrently mutated genes also suggested that convergent microevolution and adaption of P. aeruginosa occur in inpatients, and genomic diversity is associated with differences in multiple-drug-resistance profiles. Taken together, our findings highlight the importance of longitudinal surveillance of nosocomial P. aeruginosa clones.
登录
查看更多内容
开放式细菌种群基因组学：BIGSDB软件，pubmlst.org网站及其应用。
影响因子：
--
作者：
Jolley KA;Bray JE;Maiden MCJ
通讯作者：
Maiden MCJ
影响因子：
6.9
作者：
Coppry, M.;Leroyer, C.;Rogues, A-M
通讯作者：
Rogues, A-M
影响因子：
14.9
作者：
Letunic I;Bork P
通讯作者：
Bork P
影响因子：
1.2
作者：
Cingolani, Pablo;Platts, Adrian;Ruden, Douglas M.
通讯作者：
Ruden, Douglas M.
影响因子：
3.2
作者：
CUNLIFFE, HE;MERRIMAN, TR;LAMONT, IL
通讯作者：
LAMONT, IL