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Prevalence of hypermutator isolates of Achromobacter spp. from cystic fibrosis patients.

从囊性纤维化患者中分离出的无色杆菌高突变株的流行率。

  • 影响因子:2.94
  • DOI:10.1016/j.ijmm.2020.151393
  • 作者列表:"Ridderberg W","Jensen Handberg K","Nørskov-Lauritsen N
  • 发表时间:2020-01-16
Abstract

:Bacteria colonising the lungs of cystic fibrosis (CF) patients encounter high selective pressures. Hypermutation facilitates adaptation to fluctuating environments, and hypermutator strains are frequently isolated from CF patients. We investigated the prevalence of hypermutator isolates of Achromobacter spp. among patients affiliated with the CF Centre in Aarhus, Denmark. By exposure to rifampicin, the mutation frequency was determined for 90 isolates of Achromobacter spp. cultured from 42 CF patients; 20 infections were categorised as chronic, 22 as intermittent. The genetic mechanisms of hypermutation were examined by comparing DNA repair gene sequences from hypermutator and normomutator isolates. Achromobacter spp. cultured from 11 patients were categorised as hypermutators, and this phenotype was exclusively associated with chronic infections. Isolates of the Danish epidemic strain (DES) of Achromobacter ruhlandii cultured from patients from both Danish CF centres showed elevated mutation frequencies. The hypermutator state of Achromobacter spp. was most commonly associated with nonsynonymous mutations in the DNA mismatch repair gene mutS; a single clone had developed a substitution in the S-adenosyl-L-methionine-dependent methyltransferase putatively involved in DNA repair mechanisms, but not previously linked to the hypermutator phenotype. Hypermutation is prevalent among clinical isolates of Achromobacter spp. and could be a key determinant for the extraordinary adaptation and persistence of DES.

摘要

: 囊性纤维化 (CF) 患者肺部定植的细菌遇到高选择性压力。超突变有利于适应波动的环境,超突变株经常从 CF 患者中分离。我们调查了无色杆菌属超突变分离株的流行情况。在丹麦奥胡斯 CF 中心附属的患者中。通过暴露于利福平,测定 90 株无色杆菌分离株的突变频率。从 42 例 CF 患者培养; 20 例感染分为慢性,22 例为间歇性。通过比较超突变和正突变分离株的 DNA 修复基因序列,检测超突变的遗传机制。无色杆菌属。从 11 例患者中培养出来的被归类为超突变,这种表型完全与慢性感染相关。从丹麦两个 CF 中心的患者培养的无色杆菌 ruhlandii 的丹麦流行株 (DES) 分离株显示突变频率升高。无色杆菌 spp 的超突变状态。最常与 DNA 错配修复基因 mutS 的非同义突变相关; 单个克隆在 S-腺苷-L-甲硫氨酸依赖性甲基转移酶中发生了取代,推测其参与 DNA 修复机制,但以前未与超突变表型相关。超突变在无色杆菌属的临床分离株中普遍存在。并且可能是 DES 非凡适应和持久性的关键决定因素。

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影响因子:4.40
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DOI:10.1007/s00262-019-02431-8
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