A Subtype of a Pseudomonas aeruginosa Cystic Fibrosis Epidemic Strain Exhibits Enhanced Virulence in a Murine Model of Acute Respiratory Infection

被引:38
作者
Carter, Melissa E. K. [2 ]
Fothergill, Joanne L. [1 ,3 ]
Walshaw, Martin J. [4 ]
Rajakumar, Kumar [2 ]
Kadioglu, Aras [2 ]
Winstanley, Craig [1 ,3 ]
机构
[1] Univ Liverpool, Div Med Microbiol, Liverpool L69 3GA, Merseyside, England
[2] Univ Leicester, Dept Infect Immun & Infect, Leicester, Leics, England
[3] Royal Liverpool Univ Hosp, Biomed Res Ctr, Liverpool, Merseyside, England
[4] Liverpool Heart & Chest Hosp, Reg Adult Cyst Fibrosis Unit, Liverpool, Merseyside, England
关键词
CHRONIC LUNG INFECTION; CAENORHABDITIS-ELEGANS; PULMONARY INFECTION; GENETIC ADAPTATION; MOUSE MODEL; RAT MODEL; IDENTIFICATION; CF; PATHOGENESIS; PATIENT;
D O I
10.1086/655781
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:935 / 942
页数:8
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