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| Content Provider | PubMed Central |
|---|---|
| Author | Cersini, Antonella Martino, Maria Celeste Martini, Irene Rossi, Giacomo Bernardini, Maria Lina |
| Copyright Year | 2003 |
| Abstract | Several Shigella flexneri mutants with defects in aromatic amino acid and/or purine biosynthesis have been evaluated as vaccines in humans or in animal models. To be suitable as a vaccine, a mutant has to show virulence attenuation, minimal reactogenicity, and a good immunogenic potential in animal models. With this aim, we have constructed five S. flexneri 5 (wild-type strain M90T) mutants with inactivation of one or two of the loci purEK, purHD, and guaBA, governing early or late steps of purine biosynthesis. The mutants have been analyzed in vitro in cell cultures and in vivo in the Sereny test and in the murine pulmonary model of shigellosis. M90T guaBA, M90T guaBA purEK, M90T guaBA purHD, and M90T purHD purEK gave a negative result in the Sereny test. In contrast, in the murine pulmonary model all of the strains had the same 50% lethal dose as the wild type, except M90T guaBA purHD, which did not result in death of the animals. Nevertheless, bacterial counts in infected lungs, immunohistochemistry, and reverse transcription-PCR analysis of mRNAs for tumor necrosis factor alpha (TNF-α), gamma interferon (IFN-γ), interleukin-1β (IL-1β), IL-6, IL-12, and inducible nitric oxide synthase (iNOS) revealed significant differences among the strains. At 72 h postinfection, M90T guaBA purHD still induced proinflammatory cytokines and factors such as IL-1β, IL-6, TNF-α, and iNOS, along with cytokines such as IL-12 and IFN-γ. Moreover, in the absence of evident lesions in murine tissues, this mutant highly stimulated major histocompatibility complex class II expression, showing a significant ability to activate the innate immunity of the host. |
| Related Links | http://dx.doi.org/10.1128/iai.71.12.7002-7013.2003 |
| Ending Page | 7013 |
| Page Count | 12 |
| Starting Page | 7002 |
| File Format | |
| ISSN | 00199567 |
| e-ISSN | 10985522 |
| Journal | Infection and Immunity |
| Issue Number | 12 |
| Volume Number | 71 |
| Language | English |
| Publisher | American Society for Microbiology |
| Publisher Date | 2003-12-01 |
| Access Restriction | Open |
| Rights Holder | American Society for Microbiology |
| Subject Keyword | Immunology Microbiology Parasitology Infectious Diseases Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Infectious Diseases Parasitology Immunology Microbiology |
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