Abstract
The PAS-resistance-system of Mycobacterium tuberculosis var. hominis, strain Aoyama-B, has been tsudied from genetic aspect and the following conclusions have been obtained.
Survival curve for the strain plated on medium containing various concentrations of PAS represent two discontinuous points, and population structure of one-step resistant strains obtained by one-step selection with various PAS concentrations also represents a significant change of population structure at the same points. In view of the results, it has been suggested that PAS-sensitivity or PAS-resistance is determined by three genotypes: The first is the wild genotype; The second is the genotype of lower degrees of PAS-resistance (until approximately 10mcg.); and the third is the genotype of higher degrees of PAS-resistance (until approximately 200 to 500mcg.).
Mutaion rates to mutations to these resistant genotypes are approximately 10-5 and 10-8, respectively, and the mutations occur independently from each other.
Even in the presence of the same genotype, there is a significant variation of phenotypic expression. Thus, the existence of various degrees of PAS-resistance is interpreted by assuming only a few genotypes and variation of phenotypic expression. It is considered that a discontinuous change of PAS-resistance is derived from the change of genotype and a continuous change of PAS-resistance is done from the variation of phenotypic expression in the presence of the same genotype.
The growth rate of PAS-sensitive cells as well as PAS-resistant mutants varies continuously depending on the PAS concentration. Consequently, the degree of PAS-resistance varies depending on the size of inoculum and the incubation period. Therefore, it is desirable that the degree of PAS-resistance is expressed as the growth rate on a constant PAS concentration or as the highest PAS concentration, on which single cells (a constant size of inoculum giving discrete colonies on PAS-free medium) can give visible colonies after a constant incubation period.
It has been indicated that there is a phenomenon of interferrence of growth between resistant mutants and sensitive cells as well as between reistant mutants of different degrees af resistance.
