Salmonella entericaSerovar Typhimurium trxAMutants Are Protective against Virulent Challenge and Induce Less Inflammation than the Live-Attenuated Vaccine Strain SL3261

Autor: Peters, S. E., Paterson, G. K., Bandularatne, E. S. D., Northen, H. C., Pleasance, S., Willers, C., Wang, J., Foote, A. K., Constantino-Casas, F., Scase, T. J., Blacklaws, B. A., Bryant, C. E., Mastroeni, P., Charles, I. G., Maskell, D. J.
Zdroj: Infection and Immunity; January 2010, Vol. 78 Issue: 1 p326-336, 11p
Abstrakt: ABSTRACTIn Salmonella entericaserovar Typhimurium, trxAencodes thioredoxin 1, a small, soluble protein with disulfide reductase activity, which catalyzes thiol disulfide redox reactions in a variety of substrate proteins. Thioredoxins are involved as antioxidants in defense against oxidative stresses, such as exposure to hydrogen peroxide and hydroxyl radicals. We have made a defined, complete deletion of trxAin the mouse-virulent S.Typhimurium strain SL1344 (SL1344 trxA), replacing the gene with a kanamycin resistance gene cassette. SL1344 trxAwas attenuated for virulence in BALB/c mice by the oral and intravenous routes and when used in immunization experiments provided protection against challenge with the virulent parent strain. SL1344 trxAinduced less inflammation in murine spleens and livers than SL3261, the aroAmutant, live attenuated vaccine strain. The reduced splenomegaly observed following infection with SL1344 trxAwas partially attributed to a reduction in the number of both CD4+and CD8+T cells and B lymphocytes in the spleen and reduced infiltration by CD11b+cells into the spleen compared with spleens from mice infected with SL3261. This less severe pathological response indicates that a trxAmutation might be used to reduce reactogenicity of live attenuated vaccine strains. We tested this by deleting trxAin SL3261. SL3261 trxAwas also less inflammatory than SL3261 but was slightly less effective as a vaccine strain than either the SL3261 parent strain or SL1344 trxA.
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