SELECTION OF A MUTANT STRAIN OF RICKETTSIA PROWAZEKI RESISTANT TO p -AMINOBENZOIC ACID

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Abstract
A successful attempt was made to develop a PABA-resistant strain of R. prowazeki by passing the Madrid E strain in eggs in moderately inhibitory concentrations of PABA. Increased resistance was first noticed during the 4th passage and became pronounced by the 8th. A further increase in resistance was first indicated during the 24th passage, but it did not become well established until the 37th. Limit-dilution strains were then obtained from the parent rick-ettsiae and from those of the 37th passage and their characteristics compared. The PABA-resistant strain appeared to be indistinguishable from the parent in morphology and ability to elicit complement-fixing antibodies in guinea pigs. It did not lose its resistance after 10 drug-less passages. The susceptibility of the 2 strains to PABA was studied by comparing the survival times of infected chick embryos and the increment of rickettsiae in eggs which had received varying amounts of PABA. The survival time of embryos infected with the parent strain was increased by amounts of PABA of 0.2 mg or greater. An increase in the survival time of embryos infected with the resistant strain could not be clearly demonstrated with subtoxic amounts of PABA. The drug did not appear to influence the initial stages of infection with either strain, but 1 and 3 mg markedly altered the course of increment of the parent rickettsiae in eggs. The increment of the resistant strain was changed very little, if at all, by 3 mg but attainment of peak titer was delayed by 2 days with 10 mg.