Francisella tularensis is considered a potential bioterrorism agent due to its low infectious dose, high mortality rate, and ability to be spread via the aerosol route. We characterized the F. tularensis subspecies no...Francisella tularensis is considered a potential bioterrorism agent due to its low infectious dose, high mortality rate, and ability to be spread via the aerosol route. We characterized the F. tularensis subspecies novicida mutant strain FTN0109 as a potential vaccine candidate against tularemia. This strain, which lacks an outer membrane lipoprotein, is attenuated in vitro and in vivo, as it exhibits reduced replication within murine J774 macrophages and has a pulmonary LD50 in BALB/c and C57BL/6 mice of >105 CFU (compared to WT parental strain U112, LD50 FTN0109 also conferred complete protection in BALB/c mice against subsequent pulmonary challenge with 10 LD50 (60,000 CFU) of the murine virulent Francisella strain LVS. We also have demonstrated partial protection (50%) against the highly human virulent subspecies tularensis strain SCHU S4 (25 LD50, 12,500 CFU) following intratracheal vaccination in the Fischer 344 rat, a second rodent model for tularemia. Overall, our results suggest that FTN0109 serves as a potential putative vaccine candidate against pulmonary tularemia.展开更多
Objective To study the types of subspecies of Francisella tularensis from China and to investigate the genetic relationships between F. tularensis strains from China and from other countries. Methods Ten strains of F....Objective To study the types of subspecies of Francisella tularensis from China and to investigate the genetic relationships between F. tularensis strains from China and from other countries. Methods Ten strains of F. tulorensis isolated from China were amplified by using typing primers Cl/C4 and RD1. On the basis of the lengths of the polymerase chain reaction （PCR） products, it was concluded that these strains of F. tularensis belonged to the same subspecies. At the same time, thefopA, tul4, and 16S rRNA genes of the I0 strains were amplified, and a three-gene based phylogenetic analysis was performed using the Molecular Evolutionary Genetics Analysis software version 4.0. Results The 10 strains of F. tularensis from China were all identified as belonging to subspecies holarctica （type B）. We found no direct relationship between the genotypes of F. tulurensis subsp. holarctica and the geographical area from where they were isolated. Conclusion The F. tularensis strains isolated from North China mainly belong to subspecies holorctica （type B）. The strains of F. tularensis subsp, holarctico from China may have evolved earlier than those from Europe and North America.展开更多
文摘Francisella tularensis is considered a potential bioterrorism agent due to its low infectious dose, high mortality rate, and ability to be spread via the aerosol route. We characterized the F. tularensis subspecies novicida mutant strain FTN0109 as a potential vaccine candidate against tularemia. This strain, which lacks an outer membrane lipoprotein, is attenuated in vitro and in vivo, as it exhibits reduced replication within murine J774 macrophages and has a pulmonary LD50 in BALB/c and C57BL/6 mice of >105 CFU (compared to WT parental strain U112, LD50 FTN0109 also conferred complete protection in BALB/c mice against subsequent pulmonary challenge with 10 LD50 (60,000 CFU) of the murine virulent Francisella strain LVS. We also have demonstrated partial protection (50%) against the highly human virulent subspecies tularensis strain SCHU S4 (25 LD50, 12,500 CFU) following intratracheal vaccination in the Fischer 344 rat, a second rodent model for tularemia. Overall, our results suggest that FTN0109 serves as a potential putative vaccine candidate against pulmonary tularemia.
基金supported by the National Technology Key Special Study Program of the Eleventh Five‐year Plan (No. 2008ZX10004‐010)
文摘Objective To study the types of subspecies of Francisella tularensis from China and to investigate the genetic relationships between F. tularensis strains from China and from other countries. Methods Ten strains of F. tulorensis isolated from China were amplified by using typing primers Cl/C4 and RD1. On the basis of the lengths of the polymerase chain reaction （PCR） products, it was concluded that these strains of F. tularensis belonged to the same subspecies. At the same time, thefopA, tul4, and 16S rRNA genes of the I0 strains were amplified, and a three-gene based phylogenetic analysis was performed using the Molecular Evolutionary Genetics Analysis software version 4.0. Results The 10 strains of F. tularensis from China were all identified as belonging to subspecies holarctica （type B）. We found no direct relationship between the genotypes of F. tulurensis subsp. holarctica and the geographical area from where they were isolated. Conclusion The F. tularensis strains isolated from North China mainly belong to subspecies holorctica （type B）. The strains of F. tularensis subsp, holarctico from China may have evolved earlier than those from Europe and North America.
