Characterization of New and Advancement of Existing Animal Models of Bacillus anthracis Infection

Author(s):  
Elizabeth Leffel ◽  
M Pitt
mAbs ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 1954136
Author(s):  
Sujatha Kumar ◽  
Srimoyee Ghosh ◽  
Geeta Sharma ◽  
Zebin Wang ◽  
Marilyn R. Kehry ◽  
...  

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4221
Author(s):  
Aage Kristian Olsen Alstrup ◽  
Svend Borup Jensen ◽  
Ole Lerberg Nielsen ◽  
Lars Jødal ◽  
Pia Afzelius

The development of new and better radioactive tracers capable of detecting and characterizing osteomyelitis is an ongoing process, mainly because available tracers lack selectivity towards osteomyelitis. An integrated part of developing new tracers is the performance of in vivo tests using appropriate animal models. The available animal models for osteomyelitis are also far from ideal. Therefore, developing improved animal osteomyelitis models is as important as developing new radioactive tracers. We recently published a review on radioactive tracers. In this review, we only present and discuss osteomyelitis models. Three ethical aspects (3R) are essential when exposing experimental animals to infections. Thus, we should perform experiments in vitro rather than in vivo (Replacement), use as few animals as possible (Reduction), and impose as little pain on the animal as possible (Refinement). The gain for humans should by far exceed the disadvantages for the individual experimental animal. To this end, the translational value of animal experiments is crucial. We therefore need a robust and well-characterized animal model to evaluate new osteomyelitis tracers to be sure that unpredicted variation in the animal model does not lead to a misinterpretation of the tracer behavior. In this review, we focus on how the development of radioactive tracers relies heavily on the selection of a reliable animal model, and we base the discussions on our own experience with a porcine model.


1993 ◽  
Vol 268 (3) ◽  
pp. 1695-1701
Author(s):  
H. Munier ◽  
F.J. Blanco ◽  
B. Prêcheur ◽  
E. Diesis ◽  
J.L. Nieto ◽  
...  

Biochemistry ◽  
1990 ◽  
Vol 29 (20) ◽  
pp. 4922-4928 ◽  
Author(s):  
Elisabeth Labruyere ◽  
Michele Mock ◽  
Daniel Ladant ◽  
Susan Michelson ◽  
Anne Marie Gilles ◽  
...  

Blood ◽  
2002 ◽  
Vol 99 (12) ◽  
pp. 4400-4405 ◽  
Author(s):  
Suzanne Burns ◽  
Murat O. Arcasoy ◽  
Li Li ◽  
Elizabeth Kurian ◽  
Katri Selander ◽  
...  

A drug that specifically inhibits erythropoiesis would be clinically useful. The erythropoietin (Epo) mutant Epo (R103A) could potentially be used for this purpose. Epo (R103A) has a single amino acid substitution of alanine for arginine at position 103. Because of this mutation, Epo (R103A) is only able to bind to one of the 2 subunits of the erythropoietin receptor (EpoR) homodimer and is thus a competitive inhibitor of Epo activity. To produce large quantities of Epo (R103A) to test in animal models of thalassemia and sickle cell disease, we expressed and purified recombinant Epo (R103A) from the yeast Pichia pastoris. Using this method milligram quantities of highly purified Epo (R103A) are obtained. The yeast-expressed Epo (R103A) is properly processed and glycosylated and specifically inhibits Epo-dependent cell growth and125I-Epo binding. Epo (R103A) does not, however, directly induce apoptosis in 32D cells expressing EpoR. Epo (R103A) inhibits erythropoiesis of human CD34+ hematopoietic cells and completely blocks erythroid burst-forming unit formation in normal human bone marrow colony assays. Yeast-expressed Epo (R103A) is a specific inhibitor of primary erythropoiesis suitable for testing in animal models.


2014 ◽  
Vol 60 (6) ◽  
pp. 1290-1303 ◽  
Author(s):  
Peter Fickert ◽  
Marion J. Pollheimer ◽  
Ulrich Beuers ◽  
Carolin Lackner ◽  
Gideon Hirschfield ◽  
...  

Author(s):  
Victoria Hampshire ◽  
John Bacher ◽  
Melvin Dennis ◽  
Axel Wolff ◽  
Melissa Yarko

1998 ◽  
Vol 66 (2) ◽  
pp. 567-572 ◽  
Author(s):  
William R. Schwan ◽  
Silvija N. Coulter ◽  
Eva Y. W. Ng ◽  
Michael H. Langhorne ◽  
Heather D. Ritchie ◽  
...  

ABSTRACT Staphylococcus aureus is an important pathogen of humans and other animals, causing bacteremia, abscesses, endocarditis, and other infectious syndromes. A signature-tagged mutagenesis (STM) system was adapted for use in studying the genes required for in vivo survival of S. aureus. An STM library was ultimately created in S. aureus RN6390, with Tn917 being used to create the transposon mutations. Pools of S. aureusRN6390 mutants were screened in mouse abscess, bacteremia, and wound infection models for growth attenuation after in vivo passage. One of the mutants that was identified displayed marked attenuation following large-pool screening in all three animal models, which was confirmed in bacteremia and endocarditis models of infection with a smaller pool of mutants. Sequence analysis of the entire open reading frame showed a 99% identity to the high-affinity proline permease (putP) gene characterized in another strain of S. aureus. In wound and murine abscess infection models, the putP mutant was approximately 10-fold more attenuated than was wild-type strain RN6390. Another S. aureus strain transduced with theputP mutation also displayed an attenuated phenotype after passage in the wound model. A [3H]proline uptake assay showed that less proline was specifically transported into theputP mutant than into strain RN6390. The reduced viability of the bacteria possessing the mutation in the S. aureushigh-affinity proline permease suggests that proline scavenging by the bacteria is important for in vivo growth and proliferation and that analogs of proline may serve as potential antistaphylococcal therapeutic agents.


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