Hypermutability in environmental Pseudomonas aeruginosa and in populations causing pulmonary infection in individuals with cystic fibrosis

Hypermutability in environmental Pseudomonas aeruginosa and in populations causing pulmonary infection in individuals with cystic fibrosis
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DOI:
10.1099/mic.0.2006/005082-0
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发表时间:
2007-06-01
期刊:
影响因子:
2.8
通讯作者:
Govan, John R. W.
Govan, John R. W.
中科院分区:
生物学4区
文献类型:
--
作者:
Kenna, Dervla T.;Doherty, Catherine J.;Govan, John R. W.

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铜绿假单胞菌是囊性纤维化(CF)患者发病率和死亡率最常见的病原体。负责进行性CIF肺病的宿主-病原体相互作用是复杂的。然而,在细菌适应性和抗菌素耐药性方面,人们对高变铜绿假单胞菌(即由于错配修复和错误预防基因突变而突变频率增加的菌株)的作用越来越感兴趣。高变铜绿假单胞菌在慢性CIF感染中的患病率已经确定,并且高达37%。据作者所知,在感染的早期阶段,在被认为是主要感染源的环境假单胞菌中,以及在已成为主要挑战的流行菌株中,没有流行率的报告。本研究的目的是确定这些假单胞菌人群中高变铜绿假单胞菌的患病率。该假说认为,超突变在早期和环境中的铜绿假单胞菌中是罕见的,但相反,可以解释相对较新出现的流行菌株。结果发现,10/100(10%)的早期分离株是强或弱的突变体,这表明CF肺不是影响该组患者中突变体存在的唯一因素。在32株环境分离物中发现2株弱突变株(6%)。15株流行性铜绿假单胞菌中只有2株(13%)是高变的,尽管更仔细的分析表明这个问题很复杂,但总体而言,数据表明这些高传播性菌株的非典型特征不能仅仅用这种现象来解释。在早期感染和环境分离株中,突变体的患病率高于预期,这加强了CF中铜绿假单胞菌感染的早期和积极治疗的重要性。
Pseudomonas aeruginosa is the pathogen most commonly associated with morbidity and mortality in cystic fibrosis (CF) patients. The host-pathogen interactions responsible for progressive CIF lung diseases are complex. However, there is growing interest in the role of hypermutable P. aeruginosa (that is, those strains with an increased mutation frequency due to mutations in mismatch repair and error prevention genes), in terms of both bacterial adaptation and antimicrobial resistance. The prevalence of hypermutable P. aeruginosa in chronic CIF infection has been established, and at 37% is surprisingly high. To the authors' knowledge, there are no reports of prevalence during the early stages of infection, in environmental pseudomonas, which are believed to be the primary source of infection, and in epidemic strains, which have emerged as a major challenge. The aim of this study was to establish the prevalence of hypermutable P. aeruginosa in these pseudomonas populations. The hypothesis was that hypermutability would be rare in early and in environmental P. aeruginosa but in contrast would explain the relatively recent emergence of epidemic strains. It was found that 10/100 (10%) of early isolates were strong or weak mutators, suggesting that the CF lung is not the only factor influencing the existence of mutators in this group of patients. Two weak mutators (6%) were found in 32 environmental isolates. Only two of 15 (13%) epidemic P. aeruginosa strains were hypermutable, and although closer analysis revealed this issue to be complex, on the whole the data suggested that the atypical characteristics of these highly transmissible strains cannot solely be explained by this phenomenon. The higher than predicted prevalence of mutators in early infection, and in environmental isolates, reinforces the importance of early and aggressive treatment for P. aeruginosa infection in CF.