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Transcriptional profiling of Bacillus anthracis Sterne (34F2) during iron starvation.

Carlson PE, Carr KA, Janes BK, Anderson EC, Hanna PC - PLoS ONE (2009)

Bottom Line: Two genes encoding putative internalin proteins were chosen for further study.This attenuation was amplified in a double mutant strain.These data define the transcriptional changes induced during growth in low iron conditions and illustrate the potential of this dataset in the identification of putative virulence determinants for future study.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.

ABSTRACT
Lack of available iron is one of many environmental challenges that a bacterium encounters during infection and adaptation to iron starvation is important for the pathogen to efficiently replicate within the host. Here we define the transcriptional response of B. anthracis Sterne (34F(2)) to iron depleted conditions. Genome-wide transcript analysis showed that B. anthracis undergoes considerable changes in gene expression during growth in iron-depleted media, including the regulation of known and candidate virulence factors. Two genes encoding putative internalin proteins were chosen for further study. Deletion of either gene (GBAA0552 or GBAA1340) resulted in attenuation in a murine model of infection. This attenuation was amplified in a double mutant strain. These data define the transcriptional changes induced during growth in low iron conditions and illustrate the potential of this dataset in the identification of putative virulence determinants for future study.

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Attenuation of B. anthracis Δ0552, 1346 strain lacking both putative internalins.DBA/2J mice were infected by intratracheal infection with WT (circles) or Δ0552, 1346 (squares) spores at 1.5×105 spores per mouse. Mice were monitored for fourteen days, then all surviving mice were euthanized.
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pone-0006988-g006: Attenuation of B. anthracis Δ0552, 1346 strain lacking both putative internalins.DBA/2J mice were infected by intratracheal infection with WT (circles) or Δ0552, 1346 (squares) spores at 1.5×105 spores per mouse. Mice were monitored for fourteen days, then all surviving mice were euthanized.

Mentions: Although no differences in IDM growth were observed for these mutants, the combination of B. anthracis gene expression data and the fact that internalin-like proteins have been clearly linked to virulence in other pathogens led us to examine the role of these two genes in B. anthracis virulence. We sought to determine if B. anthracis strains lacking these putative internalins were attenuated for virulence in a mouse model of inhalational anthrax. Wild-type B. anthracis, Δ0552, Δ1346, and Δ0552/1346 strains were inoculated intratracheally into DBA/2J mice at various doses to determine the LD50 of each strain. The single deletion strains both exhibited attenuation in this model, with the loss of either GBAA0552 or GBAA1346 resulting in an increase in LD50 of approximately 110 and 60 times that of wild-type spores, respectively (Table 2). The double mutant exhibited the highest degree of attenuation, with an LD50 160 times that of wild-type B. anthracis. A representative survival curve for the double mutant is shown in Figure 6. This level of attenuation is comparable with what has been observed for internalin mutants in L. monocytogenes [35], [36], [37]. Further study will be required to fully elucidate the role of these proteins in the pathogenesis of B. anthracis.


Transcriptional profiling of Bacillus anthracis Sterne (34F2) during iron starvation.

Carlson PE, Carr KA, Janes BK, Anderson EC, Hanna PC - PLoS ONE (2009)

Attenuation of B. anthracis Δ0552, 1346 strain lacking both putative internalins.DBA/2J mice were infected by intratracheal infection with WT (circles) or Δ0552, 1346 (squares) spores at 1.5×105 spores per mouse. Mice were monitored for fourteen days, then all surviving mice were euthanized.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2742718&req=5

pone-0006988-g006: Attenuation of B. anthracis Δ0552, 1346 strain lacking both putative internalins.DBA/2J mice were infected by intratracheal infection with WT (circles) or Δ0552, 1346 (squares) spores at 1.5×105 spores per mouse. Mice were monitored for fourteen days, then all surviving mice were euthanized.
Mentions: Although no differences in IDM growth were observed for these mutants, the combination of B. anthracis gene expression data and the fact that internalin-like proteins have been clearly linked to virulence in other pathogens led us to examine the role of these two genes in B. anthracis virulence. We sought to determine if B. anthracis strains lacking these putative internalins were attenuated for virulence in a mouse model of inhalational anthrax. Wild-type B. anthracis, Δ0552, Δ1346, and Δ0552/1346 strains were inoculated intratracheally into DBA/2J mice at various doses to determine the LD50 of each strain. The single deletion strains both exhibited attenuation in this model, with the loss of either GBAA0552 or GBAA1346 resulting in an increase in LD50 of approximately 110 and 60 times that of wild-type spores, respectively (Table 2). The double mutant exhibited the highest degree of attenuation, with an LD50 160 times that of wild-type B. anthracis. A representative survival curve for the double mutant is shown in Figure 6. This level of attenuation is comparable with what has been observed for internalin mutants in L. monocytogenes [35], [36], [37]. Further study will be required to fully elucidate the role of these proteins in the pathogenesis of B. anthracis.

Bottom Line: Two genes encoding putative internalin proteins were chosen for further study.This attenuation was amplified in a double mutant strain.These data define the transcriptional changes induced during growth in low iron conditions and illustrate the potential of this dataset in the identification of putative virulence determinants for future study.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Immunology, University of Michigan Medical School, Ann Arbor, Michigan, United States of America.

ABSTRACT
Lack of available iron is one of many environmental challenges that a bacterium encounters during infection and adaptation to iron starvation is important for the pathogen to efficiently replicate within the host. Here we define the transcriptional response of B. anthracis Sterne (34F(2)) to iron depleted conditions. Genome-wide transcript analysis showed that B. anthracis undergoes considerable changes in gene expression during growth in iron-depleted media, including the regulation of known and candidate virulence factors. Two genes encoding putative internalin proteins were chosen for further study. Deletion of either gene (GBAA0552 or GBAA1340) resulted in attenuation in a murine model of infection. This attenuation was amplified in a double mutant strain. These data define the transcriptional changes induced during growth in low iron conditions and illustrate the potential of this dataset in the identification of putative virulence determinants for future study.

Show MeSH
Related in: MedlinePlus