Scientific Publications by FDA Staff
Infect Immun 2011 Jan;79(1):153-66
Role of purine biosynthesis in Bacillus anthracis pathogenesis and virulence.
Jenkins A, Cote C, Twenhafel N, Merkel T, Bozue J, Welkos S
Bacillus anthracis, the etiological agent of anthrax, is a spore forming, gram-positive bacterium and a category A biothreat agent. Screening of a library of transposon mutagenized B. anthracis spores identified a mutant displaying an altered phenotype which harbored a mutated gene encoding the purine biosynthetic enzyme PurH. PurH is a bifunctional protein that catalyzes the final steps in the biosynthesis of the purine inosine monophosphate. We constructed and characterized defined purH mutants of the virulent B. anthracis Ames strain. The virulence of the purH mutants were assessed in guinea pigs, mice, and rabbits. Compared to wild-type, spores of the purH mutants were as virulent in mouse intranasal and rabbit subcutaneous infection models but partially attenuated in a mouse intraperitoneal model. In contrast, the purH mutant spores were highly attenuated in guinea pigs regardless of administration route. The reduced virulence in guinea pigs was not due solely to a germination defect, as both bacilli and toxins were detected in vivo, suggesting that the significant attenuation was associated with a growth defect in vivo. We hypothesize that an intact purine biosynthetic pathway is required for virulence of B. anthracis in guinea pigs.
|Category: Journal Article|
|PubMed ID: #21041498||DOI: 10.1128/IAI.00925-10|
|Includes FDA Authors from Scientific Area(s): Biologics|
|Entry Created: 2011-10-03||Entry Last Modified: 2012-08-29|