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A Yersinia pestis tat mutant is attenuated in bubonic and small-aerosol pneumonic challenge models of infection but not as attenuated by intranasal challenge.

Bozue J, Cote CK, Chance T, Kugelman J, Kern SJ, Kijek TK, Jenkins A, Mou S, Moody K, Fritz D, Robinson CG, Bell T, Worsham P - PLoS ONE (2014)

Bottom Line: Deletion of the tatA gene resulted in several consequences for the mutant as compared to wild-type.In contrast, when mice were challenged intranasally with the mutant, very little difference in the LD50 was observed between wild-type and mutant strains.Collectively, these findings demonstrate an essential role for the Tat pathway in the virulence of Y. pestis in bubonic and small-aerosol pneumonic infection but less important role for intranasal challenge.

View Article: PubMed Central - PubMed

Affiliation: Bacteriology Division, The United States Army of Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, United States of America.

ABSTRACT
Bacterial proteins destined for the Tat pathway are folded before crossing the inner membrane and are typically identified by an N-terminal signal peptide containing a twin arginine motif. Translocation by the Tat pathway is dependent on the products of genes which encode proteins possessing the binding site of the signal peptide and mediating the actual translocation event. In the fully virulent CO92 strain of Yersinia pestis, the tatA gene was deleted. The mutant was assayed for loss of virulence through various in vitro and in vivo assays. Deletion of the tatA gene resulted in several consequences for the mutant as compared to wild-type. Cell morphology of the mutant bacteria was altered and demonstrated a more elongated form. In addition, while cultures of the mutant strain were able to produce a biofilm, we observed a loss of adhesion of the mutant biofilm structure compared to the biofilm produced by the wild-type strain. Immuno-electron microscopy revealed a partial disruption of the F1 antigen on the surface of the mutant. The virulence of the ΔtatA mutant was assessed in various murine models of plague. The mutant was severely attenuated in the bubonic model with full virulence restored by complementation with the native gene. After small-particle aerosol challenge in a pneumonic model of infection, the mutant was also shown to be attenuated. In contrast, when mice were challenged intranasally with the mutant, very little difference in the LD50 was observed between wild-type and mutant strains. However, an increased time-to-death and delay in bacterial dissemination was observed in mice infected with the ΔtatA mutant as compared to the parent strain. Collectively, these findings demonstrate an essential role for the Tat pathway in the virulence of Y. pestis in bubonic and small-aerosol pneumonic infection but less important role for intranasal challenge.

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Animal challenge data.Groups of Swiss Webster mice were challenged and survival monitored following various plague models of infection (sub-Q injections A–C; small-particle aerosol D and E; and intranasal F and G) with various strains of Y. pestis (wild-type A, D, and F; ΔtatA mutant B, E, and G; and the complemented ΔtatA mutant C). The calculated LD50 values are included in Table 3 3.
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pone-0104524-g006: Animal challenge data.Groups of Swiss Webster mice were challenged and survival monitored following various plague models of infection (sub-Q injections A–C; small-particle aerosol D and E; and intranasal F and G) with various strains of Y. pestis (wild-type A, D, and F; ΔtatA mutant B, E, and G; and the complemented ΔtatA mutant C). The calculated LD50 values are included in Table 3 3.

Mentions: The virulence of the ΔtatA mutant was assessed and compared to wild-type CO92 challenge through bubonic and pneumonic murine models (small-particle aerosol and intranasal instillation) of plague infection. From these assays, survival following challenge is shown in Fig. 6, and the LD50 values were determined for each route and summarized in Table 3.


A Yersinia pestis tat mutant is attenuated in bubonic and small-aerosol pneumonic challenge models of infection but not as attenuated by intranasal challenge.

Bozue J, Cote CK, Chance T, Kugelman J, Kern SJ, Kijek TK, Jenkins A, Mou S, Moody K, Fritz D, Robinson CG, Bell T, Worsham P - PLoS ONE (2014)

Animal challenge data.Groups of Swiss Webster mice were challenged and survival monitored following various plague models of infection (sub-Q injections A–C; small-particle aerosol D and E; and intranasal F and G) with various strains of Y. pestis (wild-type A, D, and F; ΔtatA mutant B, E, and G; and the complemented ΔtatA mutant C). The calculated LD50 values are included in Table 3 3.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4125294&req=5

pone-0104524-g006: Animal challenge data.Groups of Swiss Webster mice were challenged and survival monitored following various plague models of infection (sub-Q injections A–C; small-particle aerosol D and E; and intranasal F and G) with various strains of Y. pestis (wild-type A, D, and F; ΔtatA mutant B, E, and G; and the complemented ΔtatA mutant C). The calculated LD50 values are included in Table 3 3.
Mentions: The virulence of the ΔtatA mutant was assessed and compared to wild-type CO92 challenge through bubonic and pneumonic murine models (small-particle aerosol and intranasal instillation) of plague infection. From these assays, survival following challenge is shown in Fig. 6, and the LD50 values were determined for each route and summarized in Table 3.

Bottom Line: Deletion of the tatA gene resulted in several consequences for the mutant as compared to wild-type.In contrast, when mice were challenged intranasally with the mutant, very little difference in the LD50 was observed between wild-type and mutant strains.Collectively, these findings demonstrate an essential role for the Tat pathway in the virulence of Y. pestis in bubonic and small-aerosol pneumonic infection but less important role for intranasal challenge.

View Article: PubMed Central - PubMed

Affiliation: Bacteriology Division, The United States Army of Medical Research Institute of Infectious Diseases, Fort Detrick, Maryland, United States of America.

ABSTRACT
Bacterial proteins destined for the Tat pathway are folded before crossing the inner membrane and are typically identified by an N-terminal signal peptide containing a twin arginine motif. Translocation by the Tat pathway is dependent on the products of genes which encode proteins possessing the binding site of the signal peptide and mediating the actual translocation event. In the fully virulent CO92 strain of Yersinia pestis, the tatA gene was deleted. The mutant was assayed for loss of virulence through various in vitro and in vivo assays. Deletion of the tatA gene resulted in several consequences for the mutant as compared to wild-type. Cell morphology of the mutant bacteria was altered and demonstrated a more elongated form. In addition, while cultures of the mutant strain were able to produce a biofilm, we observed a loss of adhesion of the mutant biofilm structure compared to the biofilm produced by the wild-type strain. Immuno-electron microscopy revealed a partial disruption of the F1 antigen on the surface of the mutant. The virulence of the ΔtatA mutant was assessed in various murine models of plague. The mutant was severely attenuated in the bubonic model with full virulence restored by complementation with the native gene. After small-particle aerosol challenge in a pneumonic model of infection, the mutant was also shown to be attenuated. In contrast, when mice were challenged intranasally with the mutant, very little difference in the LD50 was observed between wild-type and mutant strains. However, an increased time-to-death and delay in bacterial dissemination was observed in mice infected with the ΔtatA mutant as compared to the parent strain. Collectively, these findings demonstrate an essential role for the Tat pathway in the virulence of Y. pestis in bubonic and small-aerosol pneumonic infection but less important role for intranasal challenge.

Show MeSH
Related in: MedlinePlus