Accurate and selective quantification of anthrax protective antigen in plasma by immunocapture and isotope dilution mass spectrometry

Solano, Maria I.; Woolfitt, Adrian R.; Boyer, Anne; Lins, Renato C.; Isbell, Katie; Gallegos-Candela, Maribel; Moura, Hércules; Pierce, Carrie L.; Barr, John R.

doi:10.1039/c8an02479k

Cited by 9 publications

(25 citation statements)

References 40 publications

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“…The level of PA was higher than that of LF and EF. As observed in RMs [ 39 , 45 , 51 , 58 ], EF concentrations tended to match those of LF and PA at the final phase of infection ( Figure 3 B). Also as observed in RMs [ 39 ], PA63 predominated, PA83 being detected only punctually.…”

Section: Toxins In Vivosupporting

confidence: 72%

“…An alternative method using mass spectrometry (MS) was recently established. PA83 and PA63 were immunopurified using magnetic beads covered with two anti-PA monoclonal antibodies (mAbs) and hydrolyzed by trypsin [ 39 ]. The specific tryptic peptides were analyzed using LC-MS/MS, with low detection limits for plasma, allowing the detection and quantification of total PA (PA83 + PA63) and PA83.…”

Section: How Does One Detect Anthrax Toxins and For What Applicatimentioning

confidence: 99%

“…For the RM that died, the LF/EF ratios ranged from 3.6 to 17.5. The study of Solano et al completed this kinetic analysis by focusing on the detection of PA83 and PA63 in the same five RMs [ 39 ]. PA63 was first detected 48 h after challenge in all RMs, at the intermediate phase of the disease ( Figure 3 B), at higher levels than LF.…”

Section: Toxins In Vivomentioning

confidence: 99%

“… ( A ) Kinetic trends of total LF and LT level in the serum of RMs with inhalation anthrax, adapted from [ 45 ]. ( B ) Kinetic trends of total LF, EF, and PA level in the serum of RMs and New Zealand white rabbits with inhalation anthrax, adapted from [ 39 , 45 , 50 , 51 , 58 ]. …”

Section: Figurementioning

confidence: 99%

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Anthrax Toxin Detection: From In Vivo Studies to Diagnostic Applications

Tournier

Rougeaux

2020

Microorganisms

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Anthrax toxins are produced by Bacillus anthracis throughout infection and shape the physiopathogenesis of the disease. They are produced in low quantities but are highly efficient. They have thus been long ignored, but recent biochemical methods have improved our knowledge in animal models. This article reviews the various methods that have been used and how they could be applied to clinical diagnosis.

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Section: Toxins In Vivosupporting

confidence: 72%

Section: How Does One Detect Anthrax Toxins and For What Applicatimentioning

confidence: 99%

Section: Toxins In Vivomentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

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Anthrax Toxin Detection: From In Vivo Studies to Diagnostic Applications

Tournier

Rougeaux

2020

Microorganisms

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“…Furthermore, most rabbits that succumb to inhalation anthrax from single high-dose exposures have detectable PA levels in the late stage blood samples [14,[22][23][24]. It has been established that inhalation anthrax is a biphasic or triphasic disease with a brief remission of bacteremia and toxemia in NHPs [25][26][27]. It is possible that inhalational anthrax in the rabbit follows the same course wherein these animals had circulating bacteria and PA during the course of the infection, but the times of bacteremia and toxemia did not coincide with the blood collections.…”

Section: Discussionmentioning

confidence: 99%

Physiological Responses to Multiple Low-Doses of Bacillus anthracis Spores in the Rabbit Model of Inhalation Anthrax

et al. 2020

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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

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