Limits...
Oxidoreductases that act as conditional virulence suppressors in Salmonella enterica serovar Typhimurium.

Anwar N, Sem XH, Rhen M - PLoS ONE (2013)

Bottom Line: However, we noted a significant copper chloride sensitivity of SPI1 T3SS mediated invasiveness that strongly depended on the presence of the scs genes.Our findings thus demonstrate that the scs gene cluster conditionally affects virulence and underscore the complex interactions between oxidoreductases of the thioredoxin superfamily in maintaining host adaptation of S.Typhimurium.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.

ABSTRACT
In Salmonella enterica serovar Typhimurium, oxidoreductases of the thioredoxin superfamily contribute to bacterial invasiveness, intracellular replication and to the virulence in BALB/c mice as well as in the soil nematode Caenorhabditis elegans. The scsABCD gene cluster, present in many but not all enteric bacteria, codes for four putative oxidoreductases of the thioredoxin superfamily. Here we have analyzed the potential role of the scs genes in oxidative stress tolerance and virulence in S. Typhimurium. An scsABCD deletion mutant showed moderate sensitization to the redox-active transition metal ion copper and increased protein carbonylation upon exposure to hydrogen peroxide. Still, the scsABCD mutant was not significantly affected for invasiveness or intracellular replication in respectively cultured epithelial or macrophage-like cells. However, we noted a significant copper chloride sensitivity of SPI1 T3SS mediated invasiveness that strongly depended on the presence of the scs genes. The scsABCD deletion mutant was not attenuated in animal infection models. In contrast, the mutant showed a moderate increase in its competitive index upon intraperitoneal challenge and enhanced invasiveness in small intestinal ileal loops of BALB/c mice. Moreover, deletion of the scsABCD genes restored the invasiveness of a trxA mutant in epithelial cells and its virulence in C. elegans. Our findings thus demonstrate that the scs gene cluster conditionally affects virulence and underscore the complex interactions between oxidoreductases of the thioredoxin superfamily in maintaining host adaptation of S. Typhimurium.

Show MeSH

Related in: MedlinePlus

Replication in RAW264.7 macrophages and mice, and invasion in ileal loops of mice.A) The ΔscsABCD does not restore replication of ΔtrxA in macrophage cell line RAW 264.7 B) The ΔscsABCD mutation shows a moderate increase in spleenic load in BALB/c mice on intraperitoneal challenge; n = number of mice C) The ΔscsABCD invades more efficiently in ileal loop ligation experiment. n = number of loops. ns = non-significant; * = p≤0.05; *** = p≤0.001. Error bars indicate standard error of the mean.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3672137&req=5

pone-0064948-g006: Replication in RAW264.7 macrophages and mice, and invasion in ileal loops of mice.A) The ΔscsABCD does not restore replication of ΔtrxA in macrophage cell line RAW 264.7 B) The ΔscsABCD mutation shows a moderate increase in spleenic load in BALB/c mice on intraperitoneal challenge; n = number of mice C) The ΔscsABCD invades more efficiently in ileal loop ligation experiment. n = number of loops. ns = non-significant; * = p≤0.05; *** = p≤0.001. Error bars indicate standard error of the mean.

Mentions: Apart from affecting invasion, TrxA strongly affects bacterial intracellular replication in RAW264.7 macrophage-like cells, as well as virulence in BALB/c mice [20]. Regarding intracellular replication in RAW264.7 cells we did not note any significant deviation for the ΔscsABCD mutant compared to the wild type (Fig. 6A).


Oxidoreductases that act as conditional virulence suppressors in Salmonella enterica serovar Typhimurium.

Anwar N, Sem XH, Rhen M - PLoS ONE (2013)

Replication in RAW264.7 macrophages and mice, and invasion in ileal loops of mice.A) The ΔscsABCD does not restore replication of ΔtrxA in macrophage cell line RAW 264.7 B) The ΔscsABCD mutation shows a moderate increase in spleenic load in BALB/c mice on intraperitoneal challenge; n = number of mice C) The ΔscsABCD invades more efficiently in ileal loop ligation experiment. n = number of loops. ns = non-significant; * = p≤0.05; *** = p≤0.001. Error bars indicate standard error of the mean.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3672137&req=5

pone-0064948-g006: Replication in RAW264.7 macrophages and mice, and invasion in ileal loops of mice.A) The ΔscsABCD does not restore replication of ΔtrxA in macrophage cell line RAW 264.7 B) The ΔscsABCD mutation shows a moderate increase in spleenic load in BALB/c mice on intraperitoneal challenge; n = number of mice C) The ΔscsABCD invades more efficiently in ileal loop ligation experiment. n = number of loops. ns = non-significant; * = p≤0.05; *** = p≤0.001. Error bars indicate standard error of the mean.
Mentions: Apart from affecting invasion, TrxA strongly affects bacterial intracellular replication in RAW264.7 macrophage-like cells, as well as virulence in BALB/c mice [20]. Regarding intracellular replication in RAW264.7 cells we did not note any significant deviation for the ΔscsABCD mutant compared to the wild type (Fig. 6A).

Bottom Line: However, we noted a significant copper chloride sensitivity of SPI1 T3SS mediated invasiveness that strongly depended on the presence of the scs genes.Our findings thus demonstrate that the scs gene cluster conditionally affects virulence and underscore the complex interactions between oxidoreductases of the thioredoxin superfamily in maintaining host adaptation of S.Typhimurium.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.

ABSTRACT
In Salmonella enterica serovar Typhimurium, oxidoreductases of the thioredoxin superfamily contribute to bacterial invasiveness, intracellular replication and to the virulence in BALB/c mice as well as in the soil nematode Caenorhabditis elegans. The scsABCD gene cluster, present in many but not all enteric bacteria, codes for four putative oxidoreductases of the thioredoxin superfamily. Here we have analyzed the potential role of the scs genes in oxidative stress tolerance and virulence in S. Typhimurium. An scsABCD deletion mutant showed moderate sensitization to the redox-active transition metal ion copper and increased protein carbonylation upon exposure to hydrogen peroxide. Still, the scsABCD mutant was not significantly affected for invasiveness or intracellular replication in respectively cultured epithelial or macrophage-like cells. However, we noted a significant copper chloride sensitivity of SPI1 T3SS mediated invasiveness that strongly depended on the presence of the scs genes. The scsABCD deletion mutant was not attenuated in animal infection models. In contrast, the mutant showed a moderate increase in its competitive index upon intraperitoneal challenge and enhanced invasiveness in small intestinal ileal loops of BALB/c mice. Moreover, deletion of the scsABCD genes restored the invasiveness of a trxA mutant in epithelial cells and its virulence in C. elegans. Our findings thus demonstrate that the scs gene cluster conditionally affects virulence and underscore the complex interactions between oxidoreductases of the thioredoxin superfamily in maintaining host adaptation of S. Typhimurium.

Show MeSH
Related in: MedlinePlus