Non-toxigenic derivatives of the Ames strain of Bacillus anthracis are fully virulent for mice: role of plasmid pX02 and chromosome in strain-dependent virulence

Abstract

The toxin-encoding plasmid pX01 and capsule-associated plasmid pX02 are required for full virulence of Bacillus anthracis in some animals. However, the non-toxigenic pX01-cured derivatives of certain anthrax strains are not completely attenuated for mice, and their virulence is strain-dependent. The strain-related differences were partially associated with plasmid pX02 as demonstrated by pX02 transductants of the attenuated vaccine strain UM23-1 cured of pX01, To determine the virulence of non-toxigenic variants of virulent strains, we isolated pX01 - derivatives of the Vollum 1 B strain and the more 'vaccine-resistant' Ames strain which carried pX02 from either Ames or Vollum 1 B. The 50% lethal dose (LD 50) values of the derivatives of both strains which carried the Ames pX02 were not significantly different from the LD 50s of the pX01 + pX02 + strains (and were lower than those of pX01 + pX02 - strains). pX02 + derivatives of strain UM23-1 were less virulent than the comparable Ames and Vollum 1 B strain derivatives, emphasizing a role for chromosomal loci in the virulence of the latter two strains. Non-toxigenic isolates which carried the Ames pX02 were more virulent for CBA/J mice than those with Vollum 1 B pX02, and the differences were mouse strain-dependent. The pX01 - pX02 + strains multiplied and achieved high concentrations systemically.