Bacillus cereus biovar anthracis causes inhalational anthrax-like disease in rabbits that is treatable with medical countermeasures.

Abstract

Bacillus anthracis is a zoonotic organism that causes the disease anthrax due to the activity of virulence factors harbored on plasmids pXO1 and pXO2. Inhalation of B. anthracis spores results in pneumonic disease that progresses quickly, and often results in lethality in the absence of medical countermeasure (MCM) intervention. Recently, reports have identified Bacillus cereus isolates that possess pXO1 and pXO2-like plasmids and cause an anthrax-like disease. These isolates have been named B. cereus biovar anthracis, or Bcbva. To evaluate disease course of Bcbva, the inhalational median lethal dose (INHLD50) was determined for two isolates, Bcbva Cameroon (CA) and Bcbva Cote d'Ivoire (CI), using the New Zealand white (NZW) rabbit inhalation anthrax model and compared to established B. anthracis inhalation data. Furthermore, disease progression and anthrax MCM efficacies were evaluated by quantifying temperature responses, bacteremia, and virulence factor production in both survivor and non-survivor animals. This study determined that the rabbit INHLD50 values for Bcbva CA and CI were similar to that published for B. anthracis Ames. The mean time to significant increase in body temperature (SIBT) and death were dose dependent for both Bcbva isolates, and all animals that succumbed to aerosol exposure displayed SIBT prior to death. Serum hyaluronic acid concentration increased prior to mortality in animals challenged with Bcbva and differences were observed in serum protective antigen concentration in animals challenged with Bcbva compared to B. anthracis. Pre-exposure vaccination with Anthrax Vaccine Adsorbed (AVA) and post-exposure prophylaxis of levofloxacin with or without AVA vaccination were effective against a challenge of ~200 INHLD50 of Bcbva CA or CI. Collectively, these data suggest that anthrax-like disease caused by Bcbva is similar to that caused by B. anthracis Ames 2084, and that currently available countermeasures are effective against inhalation exposure to Bcbva.