scholarly journals Physiological Responses to a Single Low-Dose of Bacillus anthracis Spores in the Rabbit Model of Inhalational Anthrax

Pathogens ◽  
2020 ◽  
Vol 9 (6) ◽  
pp. 461 ◽  
Author(s):  
Sarah C. Taft ◽  
Tonya L. Nichols ◽  
Stephanie A. Hines ◽  
Roy E. Barnewall ◽  
Gregory V. Stark ◽  
...  

Credible dose–response relationships are needed to more accurately assess the risk posed by exposure to low-level Bacillus anthracis contamination during or following a release. To begin to fill this knowledge gap, New Zealand White rabbits were implanted with D70-PCT telemetry transmitters and subsequently aerosol challenged with average inhaled doses of 2.86 × 102 to 2.75 × 105 colony forming units (CFU) of B. anthracis spores. Rabbits exposed to a single inhaled dose at or above 2.54 × 104 CFU succumbed with dose-dependent time to death. Death was associated with increases above baseline in heart rate, respiration rate, and body temperature and all rabbits that died exhibited bacteremia at some point prior to death. Rabbits that inhaled doses of 2.06 × 103 CFU or lower survived to the end of the study and showed no or minimal adverse changes in the measured physiological responses in response to the challenge. Moreover, no bacteremia nor toxemia were observed in rabbits that survived to the end of the study. Overall, the data indicate that challenge doses of B. anthracis below the level sufficient to establish systemic infection do not produce observable physiological responses; however, doses that triggered a response resulted in death.

Pathogens ◽  
2020 ◽  
Vol 9 (11) ◽  
pp. 877
Author(s):  
Sarah C. Taft ◽  
Tonya L. Nichols ◽  
Stephanie A. Hines ◽  
Roy E. Barnewall ◽  
Gregory V. Stark ◽  
...  

Bacillus anthracis spores that are re-aerosolized from surface deposits after initial contamination present significant health risks for personnel involved in decontamination. To model repeated exposure to low dose B. anthracis spores, three groups of seven rabbits were challenged with multiple low-doses of B. anthracis spores 5 days a week for 3 weeks. Mortality, body temperature, heart and respiration rates, hematology, C-reactive protein, bacteremia, and serum protective antigen were monitored for 21 days post-exposure after the last of multiple doses. All rabbits exposed to a mean daily dose of 2.91 × 102 colony forming units (CFU) survived and showed minimal physiological changes attributable to exposure. One of seven rabbits receiving a mean daily dose of 1.22 × 103 CFU died and four of seven receiving a mean daily dose of 1.17 × 104 CFU died. The LD50 was calculated to be 8.1 × 103 CFU of accumulated dose. Rabbits that succumbed to the higher dose exhibited bacteremia and increases above baseline in heart rate, respiration rate, and body temperature. Two rabbits in the mean daily dose group of 1.17 × 104 CFU exhibited clinical signs of inhalation anthrax yet survived. This study provides a description of lethality, pathophysiology, and pathology in a controlled multiple low-dose inhalation exposure study of B. anthracis in the rabbit model. The data suggest that the accumulated dose is important in survival outcome and that a subset of rabbits may show clinical signs of disease but fully recover without therapeutic intervention


2013 ◽  
Vol 58 (3) ◽  
pp. 1813-1815 ◽  
Author(s):  
Johanna Rivera ◽  
Alfred Morgenstern ◽  
Frank Bruchertseifer ◽  
John F. Kearney ◽  
Charles L. Turnbough ◽  
...  

ABSTRACTRadioimmunotherapy (RIT) takes advantage of the specificity and affinity of the antigen-antibody interaction to deliver microbicidal radioactive nuclides to a site of infection. In this study, we investigated the microbicidal properties of an alpha particle-emitting213Bi-labeled monoclonal antibody (MAb), EA2-1 (213Bi-EA2-1), that binds to the immunodominant antigen onBacillus anthracisspores. Our results showed that dormant spores were resistant to213Bi-EA2-1. Significant spore killing was observed following treatment with EA2-1 labeled with 300 μCi213Bi; however, this effect was not dependent on the MAb. In contrast, when spores were germinating,213Bi-EA2-1 mediated MAb-specific killing in a dose-dependent manner. Dormant spores are very resistant to RIT, and RIT should focus on targeting vegetative cells and germinating spores.


Author(s):  
Roy E. Barnewall ◽  
Jason E. Comer ◽  
Brian D. Miller ◽  
Bradford W. Gutting ◽  
Daniel N. Wolfe ◽  
...  

2005 ◽  
Author(s):  
Katherine C. Brittingham ◽  
Gordon Ruthel ◽  
Rekha G. Panchal ◽  
Claudette L. Fuller ◽  
Wilson J. Ribot

1999 ◽  
Vol 47 (2) ◽  
pp. 181-190 ◽  
Author(s):  
A. Bersényi ◽  
S. Fekete ◽  
I. Hullár ◽  
I. Kádár ◽  
M. Szilágyi ◽  
...  

Carrots were grown on soils polluted by heavy metal salts. Each particular microelement reached a high concentration [molybdenum (Mo) 39.00, cadmium (Cd) 2.30, lead (Pb) 4.01, mercury (Hg) 30.00, and selenium (Se) 36.20 mg/kg dry matter] in the carrot. In a metabolic balance trial conducted with 15 male and 15 female New Zealand White rabbits, the control animals (n = 5) were fed ad libitum with concentrate as basal diet, while the other rabbits received the basal diet and carrots containing the particular microelement. Blood samples were taken to determine the activity of serum enzymes. To investigate the metabolism of Mo, Cd, Pb, Hg and Se, samples were taken from the heart, liver, lungs, kidneys, spleen, ovaries/testicles, entire digestive tract, adipose tissue, femur, hair, faeces and urine. Carrot had significantly higher digestibility for all nutrients than the rabbit concentrate. Carrot samples of high Pb content had the lowest digestibility of crude protein. The microelements differed in their rate of accumulation in the organs examined: Mo and Cd accumulated in the kidneys, Pb in the kidneys, liver, bones and lungs, Hg in the kidneys and liver, while Se in the liver, kidneys and heart. The proportions of microelements eliminated from the body either via the faeces and urine (Mo 80.18% and Se 47.41%) or via the faeces (Cd 37.86%, Pb 66.39%, Hg 64.65%) were determined. Pathohistological examination revealed that the rate of spermatogenesis was reduced in the Mo, Cd, Pb and Hg groups compared to the control. Lead, Cd and Hg intake resulted in a considerable decrease in gamma-glutamyltransferase (GGT) and in an increase of alkaline phosphatase (ALP) activity because of damages to the kidneys and bones. All experimental treatments decreased the activity of cholinesterase (CHE) because of lesions in the liver.


2021 ◽  
Vol 22 (5) ◽  
pp. 2578
Author(s):  
Trim Lajqi ◽  
Christian Marx ◽  
Hannes Hudalla ◽  
Fabienne Haas ◽  
Silke Große ◽  
...  

Microglia, the innate immune cells of the CNS, exhibit long-term response changes indicative of innate immune memory (IIM). Our previous studies revealed IIM patterns of microglia with opposing immune phenotypes: trained immunity after a low dose and immune tolerance after a high dose challenge with pathogen-associated molecular patterns (PAMP). Compelling evidence shows that innate immune cells adopt features of IIM via immunometabolic control. However, immunometabolic reprogramming involved in the regulation of IIM in microglia has not been fully addressed. Here, we evaluated the impact of dose-dependent microglial priming with ultra-low (ULP, 1 fg/mL) and high (HP, 100 ng/mL) lipopolysaccharide (LPS) doses on immunometabolic rewiring. Furthermore, we addressed the role of PI3Kγ on immunometabolic control using naïve primary microglia derived from newborn wild-type mice, PI3Kγ-deficient mice and mice carrying a targeted mutation causing loss of lipid kinase activity. We found that ULP-induced IIM triggered an enhancement of oxygen consumption and ATP production. In contrast, HP was followed by suppressed oxygen consumption and glycolytic activity indicative of immune tolerance. PI3Kγ inhibited glycolysis due to modulation of cAMP-dependent pathways. However, no impact of specific PI3Kγ signaling on immunometabolic rewiring due to dose-dependent LPS priming was detected. In conclusion, immunometabolic reprogramming of microglia is involved in IIM in a dose-dependent manner via the glycolytic pathway, oxygen consumption and ATP production: ULP (ultra-low-dose priming) increases it, while HP reduces it.


2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Ali Oztuna ◽  
Hasan Nazir ◽  
Mehmet Baysallar

Bacillus anthracis spores are a potential threat to countries in the context of biodefense. We have already seen the destructiveness of the anthrax attacks in the recent past. This study presents an aminated-poly(vinyl chloride) (PVC-NH2) coated quartz crystal microbalance (QCM) immunosensor for simultaneous rapid detection of B. anthracis spores. PVC-NH2, synthesized in the laboratory, was used as an adhesive layer for monoclonal antibody immobilization on gold quartz crystal. The prepared QCM sensor was tested using a pathogen field strain of B. anthracis (GenBank number: GQ375871.1) under static addition and flow through procedures with different spore concentrations. Fourier transform infrared spectroscopy (FTIR-ATR) and scanning electron microscopy (SEM) were performed to characterize the surface of the sensor during the modification. Furthermore, a series of SEM micrographs were taken in order to investigate surface morphology and show the presence of the B. anthracis spores on the surface. It is concluded that B. anthracis spores can be accomplished by using amine functionalized polymer coated QCM sensors without requiring complicated immobilization procedures or expensive preliminary preparations.


2007 ◽  
Vol 9 (2) ◽  
pp. 502-513 ◽  
Author(s):  
Ian J. Glomski ◽  
Jörg H. Fritz ◽  
Selina J. Keppler ◽  
Viviane Balloy ◽  
Michel Chignard ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document