Bacterial live vaccines with graded level of attenuation achieved by antibiotic resistance mutations: transduction experiments on the functional unit of resistance, attenuation and further accompanying markers.
At least 10% of spontaneous chromosomal antibiotic resistant mutants of bacteria express a strain-dependent graded reduction of virulence; this correlates linearly with a prolonged generation time. Occasionally, these mutants are temperature sensitive or/and auxotrophe. The work described in this paper provides evidence that in such strains the resistance and the accompanying markers exist only as a functional genetic unit. In a series of transduction experiments with a pathogenic strain of Salmonella typhimurium, it was found that without exception, the resistance and the additional markers were 100% simultaneoulsy transferred. Furthermore, antibiotic-resistant Escherichia coli mutants with prolonged generation time, were isolated from faecal samples; it is thus indicated that, such innocuous mutants occur at any time in the intestine. It is concluded that concerns connecting such mutants to the possibility of resistance dissemination are unfounded; furthermore, even if transfer of resistance occurred, only attenuated strains would be disseminated.
Linde
K
K
Institute for Medical Microbiology and Epidemiology, Leipzig University, Germany.
Fthenakis
G C
GC
Fichtner
A
A
D000818:Animals; D001428:Bacterial Vaccines / Q000235:genetics* / Q000494:pharmacology; D017100:Bacteriophage P22 / Q000737:chemistry / Q000235:genetics; D015415:Biomarkers; D015169:Colony Count, Microbial; D004352:Drug Resistance, Microbial / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects / Q000235:genetics / Q000302:isolation & purification; D005243:Feces / Q000382:microbiology; D051379:Mice; D008813:Mice, Inbred ICR; D009268:Nalidixic Acid / Q000494:pharmacology; D011815:R Factors / Q000235:genetics / Q000494:pharmacology; D012293:Rifampin / Q000494:pharmacology; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics* / Q000276:immunology; D013307:Streptomycin / Q000494:pharmacology; D014161:Transduction, Genetic; D014613:Vaccines, Attenuated / Q000235:genetics / Q000494:pharmacology
D001428:Bacterial Vaccines; D015415:Biomarkers; D014613:Vaccines, Attenuated; D009268:Nalidixic Acid; D012293:Rifampin; D013307:Streptomycin