Salmonella enterica serovar typhimurium trxA mutants are protective against virulent challenge and induce less inflammation than the live-attenuated vaccine strain SL3261.

Peters, SE; Paterson, GK; Bandularatne, ESD; Northen, HC; Pleasance, S; Willers, C; Wang, J; Foote, AK; Constantino-Casas, F; Scase, TJ; Blacklaws, BA; Bryant, CE; Mastroeni, P; Charles, IG; Maskell, DJ

Salmonella enterica serovar typhimurium trxA mutants are protective against virulent challenge and induce less inflammation than the live-attenuated vaccine strain SL3261.

Peters, SE Paterson, GK Bandularatne, ESD Northen, HC Pleasance, S Willers, C Wang, J Foote, AK Constantino-Casas, F Scase, TJ Blacklaws, BA Bryant, CE Mastroeni, P Charles, IG

Maskell, DJ

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Publication Type:: Journal Article
Citation:: Infect Immun, 2010, 78 (1), pp. 326 - 336
Issue Date:: 2010-01

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Field	Value	Language
dc.contributor.author	Peters, SE	en_US
dc.contributor.author	Paterson, GK	en_US
dc.contributor.author	Bandularatne, ESD	en_US
dc.contributor.author	Northen, HC	en_US
dc.contributor.author	Pleasance, S	en_US
dc.contributor.author	Willers, C	en_US
dc.contributor.author	Wang, J	en_US
dc.contributor.author	Foote, AK	en_US
dc.contributor.author	Constantino-Casas, F	en_US
dc.contributor.author	Scase, TJ	en_US
dc.contributor.author	Blacklaws, BA	en_US
dc.contributor.author	Bryant, CE	en_US
dc.contributor.author	Mastroeni, P	en_US
dc.contributor.author	Charles, IG https://orcid.org/0000-0002-2423-1167	en_US
dc.contributor.author	Maskell, DJ	en_US
dc.date.issued	2010-01	en_US
dc.identifier.citation	Infect Immun, 2010, 78 (1), pp. 326 - 336	en_US
dc.identifier.uri	http://hdl.handle.net/10453/29767
dc.description.abstract	In Salmonella enterica serovar Typhimurium, trxA encodes 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 trxA in the mouse-virulent S. Typhimurium strain SL1344 (SL1344 trxA), replacing the gene with a kanamycin resistance gene cassette. SL1344 trxA was 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 trxA induced less inflammation in murine spleens and livers than SL3261, the aroA mutant, live attenuated vaccine strain. The reduced splenomegaly observed following infection with SL1344 trxA was 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 trxA mutation might be used to reduce reactogenicity of live attenuated vaccine strains. We tested this by deleting trxA in SL3261. SL3261 trxA was also less inflammatory than SL3261 but was slightly less effective as a vaccine strain than either the SL3261 parent strain or SL1344 trxA.	en_US
dc.language	eng	en_US
dc.relation.ispartof	Infect Immun	en_US
dc.relation.isbasedon	10.1128/IAI.00768-09	en_US
dc.subject.classification	Microbiology	en_US
dc.subject.mesh	Liver	en_US
dc.subject.mesh	Spleen	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Mice, Inbred BALB C	en_US
dc.subject.mesh	Mice, Knockout	en_US
dc.subject.mesh	Mice	en_US
dc.subject.mesh	Salmonella typhimurium	en_US
dc.subject.mesh	Salmonella Infections, Animal	en_US
dc.subject.mesh	Inflammation	en_US
dc.subject.mesh	Lipopolysaccharides	en_US
dc.subject.mesh	Bacterial Proteins	en_US
dc.subject.mesh	Salmonella Vaccines	en_US
dc.subject.mesh	Injections, Intravenous	en_US
dc.subject.mesh	Virulence	en_US
dc.subject.mesh	Mutation	en_US
dc.subject.mesh	Time Factors	en_US
dc.subject.mesh	Toll-Like Receptor 4	en_US
dc.title	Salmonella enterica serovar typhimurium trxA mutants are protective against virulent challenge and induce less inflammation than the live-attenuated vaccine strain SL3261.	en_US
dc.type	Journal Article
utslib.citation.volume	1	en_US
utslib.citation.volume	78	en_US
utslib.location.activity	United States	en_US
utslib.for	1108 Medical Microbiology	en_US
utslib.for	06 Biological Sciences	en_US
utslib.for	07 Agricultural and Veterinary Sciences	en_US
utslib.for	11 Medical and Health Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Strength - ithree - Institute of Infection, Immunity and Innovation
utslib.copyright.status	closed_access
pubs.issue	1	en_US
pubs.publication-status	Published	en_US
pubs.volume	78	en_US

Abstract:

In Salmonella enterica serovar Typhimurium, trxA encodes 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 trxA in the mouse-virulent S. Typhimurium strain SL1344 (SL1344 trxA), replacing the gene with a kanamycin resistance gene cassette. SL1344 trxA was 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 trxA induced less inflammation in murine spleens and livers than SL3261, the aroA mutant, live attenuated vaccine strain. The reduced splenomegaly observed following infection with SL1344 trxA was 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 trxA mutation might be used to reduce reactogenicity of live attenuated vaccine strains. We tested this by deleting trxA in SL3261. SL3261 trxA was 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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http://hdl.handle.net/10453/29767