FURTHER STUDIES OF DRUG-RESISTANT STRAINS OF RICKETTSIA PROWAZEKII

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Abstract
Three drug-resistant Madrid E strains of Rickettsia prowazeki were selected and some of their characteristics have been studied. The 3 strains, reisolated by limit-dilution techniques, were called (1) PABrr, denoting complete resistance to 10 mg of p-aminobenzoic acid per egg, (2) Qrr, indicating resistance to 0.5 mg of a quinoxaline compound which inhibits the parent strain in concentrations of 0.1 mg per egg, and (3) PABrrQr, resistant to both drugs. The PABrr strain was obtained from PABr, resistant to 3 but not to 10 mg of p-aminobenzoic acid per egg, following 21 egg passages in the presence of 10 mg of p-aminobenzoic acid. The Qr strain was obtained from the parent strain, following 20 egg passages in the presence of increasing concentrations of quinoxaline. The PABrrQr strain was obtained, possibly through a mechanism of genetic recombination, from a mixture of PABrr and Qr following 2 egg passages in high concentrations of both drugs. PABrrQr, in contrast to a mixture of PABrr and Qr, seemed to be fully resistant to a combination of the two drugs. The 3 drug-resistant strains produced amounts of mouse toxin, rabbit-cell hemolysin, and elicited complement fixing antibody responses in guinea pigs comparable to those of the parent strain. Differences were noted, however, when the strains were studied in chick embryos and cotton rats. Qr, although highly infectious when injected into the yolk sac, failed to kill the embryos as rapidly as the parent strain and PABrr. PABrrQr appeared to have reduced virulence and infectivity for the chick embryos, failed to kill cotton rats, and immunized them only when injected in high concentration. A connection between drug-resistance and change in other properties is suggested by the fact that the most important changes were encountered in PABrrQr, which was least exposed to selective factors.