Virulence capsular polysaccharide (Vi antigen) and Salmonella`s Pathogenicity Island type 1 and 2 TTSS (SPI-1 and SPI-2 TTSS) are important membrane virulence factors of human restricted pathogen S. Typhi. The Vi antigen modulates different proinflammatory signaling pathways in infected macrophages, microfold epithelial and dendritic cells. SPI-2 TTSS and its effectors are required for promoting bacterial intracellular survival, replication and apoptosis while SPI-1 and its effectors are associated with invasion of microfold epithelial cells. The purified Vi-antigen has been used as a vaccine against disease. It is a T cell independent antigen that induces moderate efficacy ( ̴ 55%) in adults and no efficacy in children bellow two years of age. Carrier protein conjugation of the Vi antigen has been successfully used to confer T cell dependency and to develop Vi conjugate vaccines with high efficacy, around 89% in three years, in all age groups. So far, the attenuated live vaccine with constitutive expression of Vi antigen and the SPI-2 TTSS mutant vaccine, progressed to phase 3 clinical tests. Particularly, the live attenuated vaccine with constitutive expression of Vi antigen might be also used to optimize the efficacies of other vaccines. The current preclinical studies consider also development of novel T cell independent vaccines from recombinant proteins and generalized modules for membrane antigens. An approach for future antivirulence therapy against disease might also consider the bioactive compounds with ability to inhibit TTSS secretions. It is concluded that combined approaches my successfully reduce S. Typhi infection in this new globalized era.
- MeSH
- antibakteriální látky farmakologie MeSH
- bakteriální polysacharidy antagonisté a inhibitory imunologie MeSH
- lidé MeSH
- Salmonella typhi účinky léků imunologie MeSH
- vakcíny farmakologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Antibody response to major porin proteins of S. Typhi (OmpC and OmpF) was evaluated in sera of typhoid patients (culture positive, n = 28; Widal positive, n = 16). Sera from fever patients (n = 6) having etiology other than Salmonella, and normal healthy human controls (n = 18) were also included. No significant difference between the anti-OmpC and anti-OmpF antibodies (Ab) of typhoid patients and controls was observed. The amino acid sequences of OmpC (and OmpF) porin of enterobacteria was aligned and searched for the variable regions specific to S. Typhi. Two regions, each representing one specific variable region of OmpC and OmpF, were selected (peptides for these regions were custom synthesized). The peptides were evaluated for Ab response of sera. A significantly higher level of Ab to both the peptides was observed in the sera of typhoid patients. The findings suggest that porins of S. Typhi are cross reactive and are not good markers for Ab-based diagnosis of typhoid fever, however, peptides representing the variable regions specific to S. Typhi may have greater diagnostic potential.
- MeSH
- břišní tyfus diagnóza imunologie mikrobiologie MeSH
- ELISA MeSH
- lidé MeSH
- molekulární modely MeSH
- molekulární sekvence - údaje MeSH
- peptidy chemická syntéza chemie imunologie MeSH
- poriny chemie imunologie MeSH
- protilátky bakteriální krev MeSH
- rekombinantní proteiny genetika chemie imunologie MeSH
- Salmonella typhi imunologie MeSH
- sekvence aminokyselin MeSH
- sekvenční seřazení MeSH
- specificita protilátek MeSH
- Check Tag
- lidé MeSH
- MeSH
- Brucella abortus imunologie MeSH
- brucelóza diagnóza epidemiologie MeSH
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- předškolní dítě MeSH
- Salmonella typhi imunologie MeSH
- salmonelóza diagnóza epidemiologie MeSH
- sérologické testy metody MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- předškolní dítě MeSH
- Publikační typ
- srovnávací studie MeSH
- MeSH
- antigeny bakteriální analýza MeSH
- ionizující záření MeSH
- Salmonella typhi imunologie účinky záření MeSH
- Publikační typ
- techniky in vitro MeSH
