Experimental actinomycosis: The pathogenic action of Actinomycetes in mice

Harper, Elizabeth M (1956) Experimental actinomycosis: The pathogenic action of Actinomycetes in mice. PhD thesis, University of Glasgow.

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Hitherto, laboratory investigations into the disease actinomycosis have been almost wholly restricted to cultural and serological studies of the causal organism, Actinomyces israelii. The reason for this limitation is lack of a method of inducing a satisfactory infection in laboratory animals. 2 The literature on actinomycosis contains many references to unsuccessful attempts to infect laboratory animals. There are also accounts of methods of infection which succeeded only irregularly or depended upon methods which introduced such a degree of artificiality that the resulting infections were of little value for any comparative purposes - for example, the testing of therapeutic substances that might be used. for the treatment of actinomycosis in man or domestic animals. A critical review of the relevant literature is presented. By inoculating mice with cultures of A. israelii grown in thioglycollate broth I found that lesions developed in the inoculated animals with sufficient regularity to suggest the usefulness of further investigation of the disease so produced in mice. Success in establishing a useful experimental infection in mice probably depended on three influences; (1) the use of fluid matures grown for a relatively short period (4 - 5 days), which gave high yields of infective material; (2) the U80 of "rough" strains of A. israelii; and (3) awareness that non-fatal lesions developed in the inoculated animals. 4. A comparative study of the lesions so produced in mice and of those found in natural infections of the human, subject showed moray striking points of similarity between the two. 5. Histological studies of organs of infected mice revealed the presence of abscesses in liver and spleen but not in other organs. The abscesses showed branching filaments of Actinomyces arranged in a radial disposition, giving a picture closely akin to that of the "sulphur granule" typical of the lesions found in natural infection of man, In the mouse, clubs at the edge of the lesion wore net observed; co that the picture approximated more closely to that found In man than to that observed in bovines. By killing animals at different times after inoculation I found that the abscesses underwent spontaneous regression from about 6 weeks after inoculation. 6. In fluid culture A. israelii may grow either in the rough form with long branching, a characteristic deposit, and clear supernatant or in the smooth form with diphtheroid morphology and even turbidity throughout the medium. The lesions in mice already described were produced by inoculation of the rough form. When inoculated, into mice, smooth cultures gave rise to macroscopic lesions which superficially appeared to be similar to those produced by the organism in the rough filamentous form, bat a clear difference in the tissue reaction was shown by histological examination. With smooth cultures nothing like a sulphur granule was seen, the diphtheroids did not give rise to branching filaments in the animal and large lipophagic macrophages were not seen. 7. Among the mice which recovered from the initial actinomycotic infection but died at 6 months after inoculation, some showed, tubular nephritis, which is a type of lesion not previously described in mice. Other survivors of the initial infection died at about 12 - 18 months after inoculation; these did not show the presence of tubular nephritis, Attempts were made on a limited, scale to produce tubular nephritis in mice by endotoxins of A. lsraelii, The results, though inconclusive, were suggestive they are given and discussed in the thesis, Experiments were also carried out to compare the action of two other members of the order Actinogyeetales with that of israelii upon insolation into mice, Nocardia asteroides aerobic acid-fast branching and relatively uncommon pathogen of man and animals produced a fatal infection in the mouse, Abscesses formed in liver, spleen and kidney. Contrary to what was found with A. israelii the kidney became a focal point of the experimental infection which was invariably fatal within two months. The type of lesion and tissue reactions were entirely different from those produced by A. israelii. Actinomyces graminins, the aerobic saprophyte aerobic saprophyte commonly found in grasses, had no effect upon mice, whether the inoculum employed was in the sporing or non-sporing phase. 9. The experimental infections thus produced with A. israelii in mice are reproducible if the necessary care is taken to observe the details of method emphasised in this thesis as important. The findings assist in establishing the status of the organism as an undoubted pathogen but of low virulence. The experimental infection has obvious uses in assessing the value of chemotherapy and for studying the pathology of the disease. In this connection the renal lesions would appear to merit particular attention.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Adviser: C H Browning
Keywords: Microbiology
Date of Award: 1956
Depositing User: Enlighten Team
Unique ID: glathesis:1956-73685
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 14 Jun 2019 08:56
Last Modified: 14 Jun 2019 08:56
URI: http://theses.gla.ac.uk/id/eprint/73685

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