INHIBITION BY ACETYLSALICYLIC ACID OF RICKETTSIAL STRAINS RESISTANT TOp-AMINOBENZOIC ACID

Abstract

Two p-aminobenzoic acid-resistant mutants of the Madrid E strain of Rickettsia prowazekii, pr and prr have been described in previous publications (Weiss et al., 1957; 1959). It has been shown that certain properties, such as antigenic specificity, infectivity, and virulence for the chick embryo and cotton rat, have not changed in these strains. However, when the study was extended to susceptibility to compounds chemically related to p-aminobenzoic acid, new characteristics were detected. These characteristics are described in this paper.' MATERIALS AND METHODS Rickettsiae. The Madrid E strain (Perez Ga-Ilardo and Fox, 1948) of R. prowazekii and its following substrains were used: psr, pr, and prr, which can be considered as first, second, and third-step mutants, respectively, to p-aminobenzoic acid resistance; Ar, resistant to acetylsalicylic acid; Qr, resistant to 2, 3-dimethylquinoxaline-1 ,4-dioxide; and pQr resistant to both p-aminobenzoic acid and the quinoxaline compound. The selection of these strains was described in previous publications (Weiss et al., 1957; 1959), except for psr and Ar which are described in later sections of this paper.2 Rickettsial pools were prepared from the infected yolk sacs of chick embryos and diluted in Bovarnick's isotonic solution (Bovarnick et al., 1950). Chemical compounds. The chemical compound(ls were obtained from several commercial sources. Solutions were prepared immediately before use, except for leucovorin and sulfadiazine which were received as solutions. The compounds were dissolved in distilled water with sufficient sodium 1 Some of this work was presented at the Seventh International Congress for Microbiology in Stockholm, Sweden, August 4 to 9, 1958. 2 The p-aminobenzoic acid-resistant strains were designated PABr, PABrr, and PABrrQr in a previous publication (Weiss et al., 1959).

Isolation of Rickettsia prowazekii with reduced sensitivity to gamma interferon

“…Furthermore, the virulence of the Madrid E strain has been reported to increase (9) or decrease (2) after passage in cell cultures. In addition, several drug-resistant or antibiotic-resistant substrains of R. prowazekii Madrid E have been isolated after laboratory passage of rickettsiae in the presence of paminobenzoic acid, 2,3-dimethyl quinoxaline-1,4-dioxide, acetylsalicylic acid, chloramphenicol, or erythromycin (20)(21)(22)(23)(24). Mutants resistant to erythromycin or rifampin have also been selected after exposure of R. prowazekii Madrid E to N-methyl-N'-nitro-N-nitrosoguanidine (1).…”

Growth and physiology of rickettsiae.

“…Weiss et al (124)(125)(126) passed the Madrid E strain of R. prowazeki serially in eggs in the presence of concentrations of pAB that were slightly inhibitory, and they isolated three strains that were resistant to 1, 3, and 10 mg of pAB per egg, respectively. The increased resistance to pAB was accompanied by an increased susceptibility to salicylic and acetylsalicylic acids.…”

“…Conversely, the permeases may remain the same, but the relative enzymatic requirements may shift in favor of pAB. Thus less pAB remains to compete with pHB metabolism, but pAB metabolism becomes more susceptible to competition with ASA (126). recognized in infected cells decrease almost to the vanishing point within a few days (22).…”

INCREASED RESISTANCE TO CHLORAMPHENICOL IN RICKETTSIA PROWAZEKII WITH A NOTE ON FAILURE TO DEMONSTRATE GENETIC INTERACTION AMONG STRAINS

“…The Madrid E strain (Perez Gallardo and Fox, 1948) of Rickettsia prowazekii was grown in the yolk sacs of chick embryos, and suspensions were diluted in the isotonic solution of Bovarnick, Miller, and Snyder (1950). The following substrains were used: parent, i.e., the Madrid E strain as received in our laboratory and reisolated by limit-dilution (Weiss et al, 1957); prr and Qr, resistant to p-aminobenzoic acid and quinoxaline oxide, respectively (Weiss et al, 1959b); Er, resistant to erythromycin (Weiss and Dressler, 1960a).…”