Corynebacterial Pseudotuberculosis in Mice

Abstract

Latent corynebactenai infection occurs naturally in many strains of mice. It can be evoked into the active disease, pseudotuberculosis, by a single injection of 10 mg of cortisone. The cortisone effect was tested in 21 colonies, representing 11 genetically different strains of mice. Animals of the C57B1/6, DBA/2, and RIII strains were shown to be latently infected with Corynebacterium kutscheri by the fact that they developed fatal pseudotuberculosis following cortisone treatment. Virulent C. kutscheri could not be isolated from homogenates of organs obtained from latently infected animals before cortisone administration; however, these homogenates yielded small translucent colonies of avirulent organisms. Recovery of these atypical colonies was facilitated by preincubating the organ homogenates before plating. The organisms constituting such colonies differed morphologically and immunologically from C. kutscheri, but had similar biochemical properties with the exception that they lacked urease and catalase activity. Mice treated with cortisone yielded both the avirulent bacteria and virulent C. kutscheri. The latter was the predominant organism present in the organs at the height of infection. Injection of avirulent organisms into Swiss Lynch mice, which are normally free of latent corynebacteria, occasionally established a latent infection which could be converted into corynebacterial pseudotuberculosis by cortisone. Cultures of fully virulent C. kutscheri were then obtained from the lesions. Latency was produced experimentally with a streptomycin-resistant strain of virulent C. kutscheri (CKsr) derived from the stock culture. When sublethal doses of CKsr were injected into NCS mice (Institut Pasteur colony), they induced a latent infection characterized by the presence of avirulent organisms possessing the streptomycin resistance marker. These were isolated in the form of small translucent colonies from the livers of the infected animals. Administration of cortisone to these animals subsequently evoked active infection from which virulent CKsr could be obtained. Injection of the avirulent streptomycin-resistant organisms into normal NCS mice established a latent infection which could be uniformly converted into corynebacterial pseudotuberculosis by cortisone. The virulent C. kutscheri obtained from the lesions bore the genetic marker of streptomycin resistance, thus being identical with CKsr. Except for streptomycin resistance, the avirulent organisms isolated from the experimentally induced latent infections were identical with those found in the naturally occurring latent infections. These results suggest that C. kutscheri can persist in vitro in an avirulent form which is resistant to the defense mechanisms of the host, and can thus establish a latent infection. Treatment of the animal with cortisone results in the conversion of the avirulent form into virulent C. kutscheri, and of the latent infection into active corynebacterial pseudotuberculosis. The findings are discussed with regard to their relevance to infection immunity, and to the conversion of latent infection into overt disease.

Corynebacterium kutscheriand its alleged avirulent variant in mice

“…Remarkably few challenge organisms were detected in the kidneys of mice immunized with strain CM23Fdr. DISCUSSION We have shown that in general the susceptibilities of the two mouse strains were as described nearly 10 years earlier Pierce-Chase et al 1964); Swiss Lynch mice were susceptible to virulent C. kutscheri infection whereas C57BI/6 mice were resistant. There was a difference of nearly 100-fold in LD 50 for C. kutscheri between the two parental strains; their Fl hybrid was intermediate.…”

“…In a subsequent paper (Hirst & Olds, 1978) we present evidence that the avirulent organism is not a variant of C. kutscheri but a streptococcus of Group N. If these two organisms are unrelated how can one explain the previous reports Pierce-Chase et at. 1964) that cortisone evoked the clinical disease in mice given the alleged variant?…”

“…1964) that cortisone evoked the clinical disease in mice given the alleged variant? We suggest that C. kutscheri, which is an insidious infiltrator into mouse colonies even under the best regulated circumstances, may have established itself unbeknown into mouse colonies other than those already heavily infected Lynch et al 1965; Pierce-Chase et al 1964). Such a possibility could have accounted for the results of the preliminary experiments reported by Fauve et al (1964) before the use of geneticallymarked streptomycin-resistant organisms.…”

“…We suggest that C. kutscheri, which is an insidious infiltrator into mouse colonies even under the best regulated circumstances, may have established itself unbeknown into mouse colonies other than those already heavily infected Lynch et al 1965; Pierce-Chase et al 1964). Such a possibility could have accounted for the results of the preliminary experiments reported by Fauve et al (1964) before the use of geneticallymarked streptomycin-resistant organisms. Injection of the alleged 'variant' into such mice latently infected with C. kutscheri and then subsequent immunosuppression with hydrocortisone acetate could have re-activated a pre-existing latent infection with C. kutscheri.…”

“…The C. kutscheri strains were obtained from the following sources: Strain CM1: from Dr C. Pierce-Chase, Rockefeller University, Strain K, isolated from the lung of a mouse, considered to be virulent C. kutscheri Pierce-Chase et al 1964 Strain GNS: from Dr C. S. Pierce-Chase, Rockefeller University, Strain A; it had been isolated from the lung of a normal mouse and was considered to be an avirulent variant of C. kutscheri Pierce-Chase et al 1964 Preparation of live vaccine and challenge strains C. kutscheri strain CM23Fdr was of considerably reduced virulence for mice and was therefore used as a vaccine strain. A single colony was seeded into digest broth with 2 % fetal calf serum and agitated gently for 18 h at 37 0C.…”