A Subtype of a Pseudomonas aeruginosa Cystic Fibrosis Epidemic Strain Exhibits Enhanced Virulence in a Murine Model of Acute Respiratory Infection
A Subtype of a Pseudomonas aeruginosa Cystic Fibrosis Epidemic Strain Exhibits Enhanced Virulence in a Murine Model of Acute Respiratory Infection
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DOI：
10.1086/655781
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发表时间：
2010-09-15
影响因子：
6.4
通讯作者：
Winstanley, Craig
中科院分区：
文献类型：
--
作者：
Carter, Melissa E. K.;Fothergill, Joanne L.;Winstanley, Craig
背景铜绿假单胞菌的利物浦流行株（LES）是一种特别成功的囊性纤维化（CF）病原体，其与可传播性、患者发病率增加以及CF患者的非CF父母的不寻常感染相关。使用测定毒力相关的外产物，生物膜形成，秀丽隐杆线虫杀伤，和急性呼吸道感染的小鼠模型，我们比较了代表的4个亚型的LES，包括LES431，分离与感染的父母没有CF。群体感应缺陷型lasR突变体LES400产生较少的外产物，并且具有较少的C。elegans的杀伤活性高于其他LES亚型，其由LES431、LESB 58和LESB 65代表。与其他LES亚型相比，LES431缺乏生物膜形成。LES亚型在小鼠模型中显示出一定范围的毒力，其中LES 431是迄今为止毒力最强的。基因组测序分离株LESB 58在慢性感染大鼠模型中有效建立感染，是小鼠急性感染模型中毒力最低的亚型。LES分离株表现出广泛变异的致病特性。LES431，与传播给CF患者的非CF父母有关，代表了一种比慢性感染更适合急性感染的“高毒力”亚型。
Background. The Liverpool epidemic strain (LES) of Pseudomonas aeruginosa is a particularly successful cystic fibrosis (CF) pathogen associated with transmissibility, increased patient morbidity, and, unusually, infection of the non-CF parents of a patient with CF.Methods. Using assays for virulence-associated exoproducts, biofilm formation, Caenorhabditis elegans killing, and a murine model of acute respiratory infection, we compared the pathogenic behavior of representatives of 4 subtypes of the LES, including LES431, an isolate associated with the infection of a parent without CF.Results. The quorum-sensing-defective lasR mutant LES400 produced less exoproduct and had less C. elegans killing activity than the other LES subtypes, which were represented by LES431, LESB58, and LESB65. LES431 was deficient in biofilm formation, compared with the other LES sub-types. The LES subtypes displayed a range of virulence in the mouse model, with LES431 being by far the most virulent. The genome-sequenced isolate LESB58, effective at establishing infections in a rat model of chronic infection, was the least virulent subtype in the murine acute infection model.Conclusions. LES isolates display widely variable pathogenic characteristics. LES431, associated with transmission to the non-CF parent of a CF patient, represents a "hypervirulent" subtype more adapted to acute infections than chronic infections.