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

Sensitivity to copper chloride, zinc chloride and hydrogen peroxide.A) Optical densities of overnight wild type S. Typhimurium and different scs mutants grown in the presence of CuCl2. This sensitivity is reversed by trans-complementation using the cloned scsABCD genes on plasmid pNA10 for ΔscsABCD mutant. B) shows equal sensitization to ZnCl2 for wild type S. Typhimurium and its Δscs mutants. C) Loss in viable count of the wild type S. Typhimurium strain after exposure to H2O2. Values are given as percentage relative to a hydrogen peroxide deficient control. *** = p≤0.001 D) Relative indices of viable counts of different scs knockouts compared to wild type reveals sensitization only for the ΔscsA mutant. ** = p≤0.01, *** = 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-g002: Sensitivity to copper chloride, zinc chloride and hydrogen peroxide.A) Optical densities of overnight wild type S. Typhimurium and different scs mutants grown in the presence of CuCl2. This sensitivity is reversed by trans-complementation using the cloned scsABCD genes on plasmid pNA10 for ΔscsABCD mutant. B) shows equal sensitization to ZnCl2 for wild type S. Typhimurium and its Δscs mutants. C) Loss in viable count of the wild type S. Typhimurium strain after exposure to H2O2. Values are given as percentage relative to a hydrogen peroxide deficient control. *** = p≤0.001 D) Relative indices of viable counts of different scs knockouts compared to wild type reveals sensitization only for the ΔscsA mutant. ** = p≤0.01, *** = p≤0.001. Error bars indicate standard error of the mean.

Mentions: The ΔscsA mutant did not reveal CuCl2 sensitivity while deleting either the scsB, scsC or scsD gene resulted in a moderate but equal and highly reproducible sensitization to CuCl2 (Fig. 2A). Similarly, the ΔscsABCD quadruple deletion mutant showed the same sensitization as the individual ΔscsB, ΔscsC and ΔscsD mutants (Fig. 2A).


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

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

Sensitivity to copper chloride, zinc chloride and hydrogen peroxide.A) Optical densities of overnight wild type S. Typhimurium and different scs mutants grown in the presence of CuCl2. This sensitivity is reversed by trans-complementation using the cloned scsABCD genes on plasmid pNA10 for ΔscsABCD mutant. B) shows equal sensitization to ZnCl2 for wild type S. Typhimurium and its Δscs mutants. C) Loss in viable count of the wild type S. Typhimurium strain after exposure to H2O2. Values are given as percentage relative to a hydrogen peroxide deficient control. *** = p≤0.001 D) Relative indices of viable counts of different scs knockouts compared to wild type reveals sensitization only for the ΔscsA mutant. ** = p≤0.01, *** = 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-g002: Sensitivity to copper chloride, zinc chloride and hydrogen peroxide.A) Optical densities of overnight wild type S. Typhimurium and different scs mutants grown in the presence of CuCl2. This sensitivity is reversed by trans-complementation using the cloned scsABCD genes on plasmid pNA10 for ΔscsABCD mutant. B) shows equal sensitization to ZnCl2 for wild type S. Typhimurium and its Δscs mutants. C) Loss in viable count of the wild type S. Typhimurium strain after exposure to H2O2. Values are given as percentage relative to a hydrogen peroxide deficient control. *** = p≤0.001 D) Relative indices of viable counts of different scs knockouts compared to wild type reveals sensitization only for the ΔscsA mutant. ** = p≤0.01, *** = p≤0.001. Error bars indicate standard error of the mean.
Mentions: The ΔscsA mutant did not reveal CuCl2 sensitivity while deleting either the scsB, scsC or scsD gene resulted in a moderate but equal and highly reproducible sensitization to CuCl2 (Fig. 2A). Similarly, the ΔscsABCD quadruple deletion mutant showed the same sensitization as the individual ΔscsB, ΔscsC and ΔscsD mutants (Fig. 2A).

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