| RRC ID |
35650
|
| 著者 |
Rasmussen JA, Post DM, Gibson BW, Lindemann SR, Apicella MA, Meyerholz DK, Jones BD.
|
| タイトル |
Francisella tularensis Schu S4 lipopolysaccharide core sugar and O-antigen mutants are attenuated in a mouse model of tularemia.
|
| ジャーナル |
Infect Immun
|
| Abstract |
The virulence factors mediating Francisella pathogenesis are being investigated, with an emphasis on understanding how the organism evades innate immunity mechanisms. Francisella tularensis produces a lipopolysaccharide (LPS) that is essentially inert and a polysaccharide capsule that helps the organism to evade detection by components of innate immunity. Using an F. tularensis Schu S4 mutant library, we identified strains that are disrupted for capsule and O-antigen production. These serum-sensitive strains lack both capsule production and O-antigen laddering. Analysis of the predicted protein sequences for the disrupted genes (FTT1236 and FTT1238c) revealed similarity to those for waa (rfa) biosynthetic genes in other bacteria. Mass spectrometry further revealed that these proteins are involved in LPS core sugar biosynthesis and the ligation of O antigen to the LPS core sugars. The 50% lethal dose (LD50) values of these strains are increased 100- to 1,000-fold for mice. Histopathology revealed that the immune response to the F. tularensis mutant strains was significantly different from that observed with wild-type-infected mice. The lung tissue from mutant-infected mice had widespread necrotic debris, but the spleens lacked necrosis and displayed neutrophilia. In contrast, the lungs of wild-type-infected mice had nominal necrosis, but the spleens had widespread necrosis. These data indicate that murine death caused by wild-type strains occurs by a mechanism different from that by which the mutant strains kill mice. Mice immunized with these mutant strains displayed >10-fold protective effects against virulent type A F. tularensis challenge.
|
| 巻・号 |
82(4)
|
| ページ |
1523-39
|
| 公開日 |
2014-4-1
|
| DOI |
10.1128/IAI.01640-13
|
| PII |
IAI.01640-13
|
| PMID |
24452684
|
| PMC |
PMC3993386
|
| MeSH |
Amino Acid Sequence
Animals
Bacterial Capsules / physiology
Disease Models, Animal
Female
Francisella tularensis / genetics
Francisella tularensis / immunology
Francisella tularensis / pathogenicity*
Lipopolysaccharides / immunology
Macrophages / cytology
Mice
Mice, Inbred C57BL
Mutation
O Antigens / chemistry
O Antigens / genetics*
O Antigens / immunology
Sequence Analysis, DNA
Tularemia / genetics
Tularemia / immunology
Tularemia / microbiology*
Virulence / genetics
Virulence / immunology
Virulence Factors / genetics
Virulence Factors / immunology
Virulence Factors / metabolism
|
| IF |
3.201
|
| 引用数 |
16
|
|
WOS 分野
|
INFECTIOUS DISEASES
IMMUNOLOGY
|
| リソース情報 |
| 原核生物(大腸菌) |
Keio collection |
