Experimental studies on a mouse model, of attenuated mutants of a Pasteurella multocida strain pathogenic to calves. 5. Spontaneous chromosomal resistance to antibiotics as a possibility for the isolation of attenuated clones
Linde, K.
Archiv für Experimentelle Veterinarmedizin 36(5): 647-656
1982
ISSN/ISBN: 0003-9055 PMID: 7165450 Document Number: 185504
Spontaneous mutants of ribonucleic acid (RNA) polymerase (with resistance to rifampicin), gyrase (with resistance to nalidixic acid), and ribosomes (with resistance to oleandomycin, lincomycin, and erythromycin) of P. multocida were tested for virulence in an intraperitoneal mouse model. The "resistance" clones broke down, depending on the antibiotic used, into a spectrum of strains with more or less strongly pronounced attenuation. Minor reduction of virulence (one-marker clones of resistance to rifampicin, nalidixic acid, and oleandomycin) was identifiable only by prolongation of extinction time. Mice which survived by strong attenuation (resistance to lincomycin and erythromycin) usually were not protected when exposed to wild strains, which was ascribed to over-attenuation of mutants. Potential double-marker or triple-marker vaccine strains, which protected the mouse model from lethal wild strain infection, could be produced by stepwise incorporation of two weakly attenuating mutations into the wild Pasteurella strain or by additional incorporation of a weakly attenuating "resistance" mutation into a highly immunogenic mutant. Potential Pasteurella vaccine srains with mutated subunits of RNA polymerase, gyrase, and ribosomes are described. Reference is made to the problem of "translation of mouse model experience to farm animals", and suggestions are made about the molecular-biological background of the "resistance" attenuation phenomenon.