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.

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 1B strain and the more 'vaccine-resistant' Ames strain which carried pX02 from either Ames or Vollum 1B. The 50% lethal dose (LD50) values of the derivatives of both strains which carried the Ames pX02 were not significantly different from the LD50s 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 1B 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 1B pX02, and the differences were mouse strain-dependent. The pX01- pX02+ strains multiplied and achieved high concentrations systemically.