Toxin and capsule production by Bacillus cereus biovar anthracis influence pathogenicity in macrophages and animal models.

Publisher: Public Library of Science Country of Publication: United States NLM ID: 101291488 Publication Model: eCollection Cited Medium: Internet ISSN: 1935-2735 (Electronic) Linking ISSN: 19352727 NLM ISO Abbreviation: PLoS Negl Trop Dis Subsets: MEDLINE

Original Publication: San Francisco, CA : Public Library of Science

Macrophages*/microbiology ; Bacillus cereus*/pathogenicity ; Bacillus cereus*/genetics ; Bacillus cereus*/physiology ; Bacillus cereus*/metabolism ; Bacterial Capsules*/metabolism ; Bacterial Capsules*/genetics ; Bacterial Toxins*/genetics ; Bacterial Toxins*/metabolism ; Antigens, Bacterial*/genetics ; Antigens, Bacterial*/metabolism ; Anthrax*/microbiology ; Bacillus anthracis*/pathogenicity ; Bacillus anthracis*/genetics ; Bacillus anthracis*/metabolism ; Bacillus anthracis*/physiology ; Spores, Bacterial*; Animals ; Mice ; Disease Models, Animal ; Guinea Pigs ; Virulence ; Female ; Humans

Competing Interests: The authors have declared that no competing interests exist.
Bacillus cereus biovar anthracis (Bcbva) causes anthrax-like disease in animals, particularly in the non-human primates and great apes of West and Central Africa. Genomic analyses revealed Bcbva as a member of the B. cereus species that carries two plasmids, pBCXO1 and pBCXO2, which have high sequence homology to the B. anthracis toxin and polyglutamate capsule encoding plasmids pXO1 and pXO2, respectively. To date, only a few studies have investigated the effect of variations in Bcbva sporulation, toxin, and capsule synthesis on animal and macrophage pathogenicity compared to B. anthracis, therefore more research is needed to gain a better understanding of the pathogenesis of this emerging infection. Here, we report that Bcbva can multiply and vegetatively survive on nutrient-rich media for a minimum of six days while generating spores. Sporulation of Bcbva occurred faster and more extensively than B. anthracis Ames. Bcbva tended to secrete less protective antigen (PA) than B. anthracis Ames when cultured in growth medium. We found Bcbva produced a substantially higher amount of attached poly-ƴ-D-glutamic acid (PDGA) capsule than B. anthracis Ames when grown in medium supplemented with human serum and CO2. In a phagocytosis assay, Bcbva spores showed reduced internalization by mouse macrophages compared to B. anthracis Ames. Our research demonstrated that Bcbva is more virulent than B. anthracis Ames using two in vivo models, Galleria mellonella larvae and guinea pigs. Following that, the efficacy of the veterinary vaccine Sterne strain 34F2 against anthrax-like disease was assessed in guinea pigs. Sterne vaccinated guinea pigs had significantly increased anti-PA titers compared to the unvaccinated control group. Toxin neutralizing antibody titers in vaccinated guinea pigs correlated with anti-PA titers. This indicates the Sterne vaccine provides adequate protection against Bcbva infection in laboratory animals.
(Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.)

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0 (Bacterial Toxins)
0 (Antigens, Bacterial)
0 (anthrax toxin)

Date Created: 20241223 Date Completed: 20250108 Latest Revision: 20250109

20250110

PMC11706511

10.1371/journal.pntd.0012779

39715264