[High-immunogenic mutants of Salmonella with two independently of each other attenuating markers as potential vaccines from bacteria capable of multiplication. 2. Communication: spontaneous chromosomal resistance against antibiotics as a possibility for isolation of clones with decreased virulence (author's transl)].

Abstract

Mutants of Salmonella typhimurium with spontaneous chromosomal resistance against oleandomycin, streptothricin, nalidixic acid and rifampicin were investigated for their virulence behaviour with the i.p. mouse model. The strains resistant against the special antibiotic consists of a spectrum of various clones with a different behaviour of virulence: Additionally to obvious unchanged virulent strains there are such with a weak or strong attenuation. The majority of the attenuated strains protect the immunized mice against a following lethal wild strain infection. High-immunogenic attenuated double-marker mutants for application as potential vaccine strains may be isolated with the aid of a step by step introduction of a second attenuating "resistance"-marker in a one-marker strain, attenuated for another reason. These strains show the following parameters: -stability under the conditions of practical vaccine application, because a simultaneous back-mutation in both attenuating markers by reason of the unrealizable germ numbers will not occur, -immunogenicity by one immunization only, -separation from homologous wild strains of another origin with simple laboratory methods. This obvious generally acting biological principle is explained on the basis of molecular biological considerations and by referring to the literature. A test for orientation using an attenuated RNA-polymerase mutant showed, the resistance against rifampicin and attenuation are transferred together by co-transduction.