scholarly journals Brucella abortus Δ rpoE1 confers protective immunity against wild type challenge in a mouse model of brucellosis

Vaccine ◽  
2016 ◽  
Vol 34 (42) ◽  
pp. 5073-5081 ◽  
Author(s):  
Jonathan W. Willett ◽  
Julien Herrou ◽  
Daniel M. Czyż ◽  
Jason X. Cheng ◽  
Sean Crosson
Keyword(s):  
Mouse Model ◽  
Brucella Abortus ◽  
Protective Immunity ◽  
Wild Type

scholarly journals Evaluation of Protection Afforded by Brucella abortus and Brucella melitensis Unmarked Deletion Mutants Exhibiting Different Rates of Clearance in BALB/c Mice

2006 ◽  
Vol 74 (7) ◽  
pp. 4048-4057 ◽  
Author(s):  
M. M. Kahl-McDonagh ◽  
T. A. Ficht
Keyword(s):  
Mouse Model ◽  
Brucella Abortus ◽  
Protective Immunity ◽  
Brucella Melitensis ◽  
Deletion Mutants ◽  
Heterologous Challenge ◽  
Current Vaccine ◽  
Protection Against Infection ◽  
Ideal Vaccine

ABSTRACT Research for novel Brucella vaccines has focused upon the development of live vaccine strains, which have proven more efficacious than killed or subunit vaccines. In an effort to develop improved vaccines, signature-tagged mutant banks were screened to identify mutants attenuated for survival. Mutants selected from these screens exhibited various degrees of attenuation characterized by the rate of clearance, ranging from a failure to grow in macrophages after 24 h of infection to a failure to persist in the mouse model beyond 8 weeks. Ideal vaccine candidates should be safe to the host, while evoking protective immunity. In the present work, we constructed unmarked deletion mutants of three gene candidates, manBA, virB2, and asp24, in both Brucella abortus and Brucella melitensis. The Δasp24 mutants, which persist for extended periods in vivo, are superior to current vaccine strains and to other deletion strains tested in the mouse model against homologous challenge infection after 12, 16, and 20 weeks postvaccination. The Δasp24 mutants also display superior protection compared to ΔmanBA and ΔvirB2 mutants against heterologous challenge in mice. From this study, a direct association between protection against infection and cytokine response was not apparent between all vaccine groups and, therefore, correlates of protective immunity will need to be considered further. A distinct correlation between persistence of the vaccine strain and protection against infection was corroborated.

scholarly journals The Brucella abortus xthA-1 Gene Product Participates in Base Excision Repair and Resistance to Oxidative Killing but Is Not Required for Wild-Type Virulence in the Mouse Model

2006 ◽  
Vol 188 (4) ◽  
pp. 1295-1300 ◽  
Author(s):  
Michael L. Hornback ◽  
R. Martin Roop
Keyword(s):  
Mouse Model ◽  
Oxidative Damage ◽  
Gene Product ◽  
Base Excision Repair ◽  
Brucella Abortus ◽  
Excision Repair ◽  
Wild Type ◽  
Exonuclease Iii ◽  
Increased Sensitivity ◽  
Base Excision

ABSTRACT Exonuclease III, encoded by the xthA gene, plays a central role in the base excision pathway of DNA repair in bacteria. Studies with Escherichia coli xthA mutants have also shown that exonuclease III participates in the repair of oxidative damage to DNA. An isogenic xthA-1 mutant (designated CAM220) derived from virulent Brucella abortus 2308 exhibited increased sensitivity to the alkylating agent methyl methanesulfonate (MMS) compared to the parent strain. In contrast, 2308 and the isogenic xthA-1 mutant displayed similar levels of resistance to the DNA cross-linker mitomycin C. These phenotypic properties are those that would be predicted for a strain defective in base excision repair. The B. abortus xthA-1 mutant also displayed reduced resistance to killing by H2O2 and the ONOO−-generating compound 3-morpholinosydnonimine (SIN-1) compared to strain 2308, indicating that the xthA-1 gene product participates in protecting B. abortus 2308 from oxidative damage. Introducing a plasmid-borne copy of the parental xthA-1 gene into CAM220 restored wild-type resistance of this mutant to MMS, H2O2, and SIN-1. Although the B. abortus xthA-1 mutant exhibited increased sensitivity to oxidative killing compared to the parental strain in laboratory assays, CAM220 and 2308 displayed equivalent spleen colonization profiles in BALB/c mice through 8 weeks postinfection and equivalent intracellular survival and replication profiles in cultured murine macrophages. Thus, although the xthA-1 gene product participates in base excision repair and resistance to oxidative killing in B. abortus 2308, XthA-1 is not required for wild-type virulence of this strain in the mouse model.

scholarly journals Brucella abortus HtrA Functions as an Authentic Stress Response Protease but Is Not Required for Wild-Type Virulence in BALB/c Mice

2001 ◽  
Vol 69 (9) ◽  
pp. 5911-5913 ◽  
Author(s):  
Robert W. Phillips ◽  
R. Martin Roop
Keyword(s):  
Stress Response ◽  
Mouse Model ◽  
Brucella Abortus ◽  
Parental Strain ◽  
Biological Function ◽  
Critical Role ◽  
Wild Type ◽  
Secondary Line

ABSTRACT A second mutation has recently been identified in the previously described Brucella abortus htrA mutant PHE1. As a result of this finding, a new B. abortus htrAmutant, designated RWP11, was constructed to evaluate the biological function of the Brucella HtrA protease. RWP11 is more sensitive to oxidative killing in vitro and less resistant to killing by cultured murine neutrophils and macrophages than the virulent parental strain 2308 but is not attenuated in BALB/c mice through 4 weeks postinfection. The in vitro phenotype of B. abortusRWP11 is consistent with the proposed function of bacterial HtrA proteases as components of a secondary line of defense against oxidative damage. The in vivo phenotype of this mutant, however, indicates that, unlike the corresponding Salmonellaand Yersinia proteins, Brucella HtrA does not play a critical role in virulence in the mouse model.

scholarly journals Intact Purine Biosynthesis Pathways Are Required for Wild-Type Virulence of Brucella abortus 2308 in the BALB/c Mouse Model

2004 ◽  
Vol 72 (8) ◽  
pp. 4911-4917 ◽  
Author(s):  
Rosemarie B. Alcantara ◽  
Richard D. A. Read ◽  
Michelle Wright Valderas ◽  
Timothy D. Brown ◽  
R. Martin Roop
Keyword(s):  
Mouse Model ◽  
Brucella Abortus ◽  
Purine Biosynthesis ◽  
Wild Type ◽  
Murine Macrophages ◽  
Significant Attenuation ◽  
Experimental Findings ◽  
Isogenic Mutants

ABSTRACT Brucella abortus 2308 derivatives with mini-Tn5 insertions in purE, purL, and purD display significant attenuation in the BALB/c mouse model, while isogenic mutants with mini-Tn5 insertions in pheA, trpB, and dagA display little or no attenuation in cultured murine macrophages or mice. These experimental findings confirm the importance of the purine biosynthesis pathways for the survival and replication of the brucellae in host macrophages. In contrast to previous reports, however, these results indicate that exogenous tryptophan and phenylalanine are available for use by the brucellae in the phagosomal compartment.

[18F]-florbetaben PET/CT Imaging in the Alzheimer’s Disease Mouse Model APPswe/PS1dE9

2018 ◽  
Vol 16 (1) ◽  
pp. 49-55 ◽  
Author(s):  
J. Stenzel ◽  
C. Rühlmann ◽  
T. Lindner ◽  
S. Polei ◽  
S. Teipel ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
New Drugs ◽  
Imaging Data ◽  
Wild Type ◽  
Preclinical Research ◽  
Standardized Uptake Values ◽  
Pet Ct

Background: Positron-emission-tomography (PET) using 18F labeled florbetaben allows noninvasive in vivo-assessment of amyloid-beta (Aβ), a pathological hallmark of Alzheimer’s disease (AD). In preclinical research, [<sup>18</sup>F]-florbetaben-PET has already been used to test the amyloid-lowering potential of new drugs, both in humans and in transgenic models of cerebral amyloidosis. The aim of this study was to characterize the spatial pattern of cerebral uptake of [<sup>18</sup>F]-florbetaben in the APPswe/ PS1dE9 mouse model of AD in comparison to histologically determined number and size of cerebral Aβ plaques. Methods: Both, APPswe/PS1dE9 and wild type mice at an age of 12 months were investigated by smallanimal PET/CT after intravenous injection of [<sup>18</sup>F]-florbetaben. High-resolution magnetic resonance imaging data were used for quantification of the PET data by volume of interest analysis. The standardized uptake values (SUVs) of [<sup>18</sup>F]-florbetaben in vivo as well as post mortem cerebral Aβ plaque load in cortex, hippocampus and cerebellum were analyzed. Results: Visual inspection and SUVs revealed an increased cerebral uptake of [<sup>18</sup>F]-florbetaben in APPswe/ PS1dE9 mice compared with wild type mice especially in the cortex, the hippocampus and the cerebellum. However, SUV ratios (SUVRs) relative to cerebellum revealed only significant differences in the hippocampus between the APPswe/PS1dE9 and wild type mice but not in cortex; this differential effect may reflect the lower plaque area in the cortex than in the hippocampus as found in the histological analysis. Conclusion: The findings suggest that histopathological characteristics of Aβ plaque size and spatial distribution can be depicted in vivo using [<sup>18</sup>F]-florbetaben in the APPswe/PS1dE9 mouse model.

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