According to our concepts, it mainly owes to characteristic properties of tubercle bacilli themselves that various and complicated reactions appear during the course of tuberculosis in animals or patients.
In general, these mycobacteria) cells contain a lot of lipoidal material, of which biological and biochemical roles in tuberculosis are being clarified recently, Here, our biochemical aspects on some of such biological reactions, originated from the infection of tubercle bacilli, will be presented in this special lecture.
1) Virulence of tubercle bacilli The properties which seem to have an close correlation to the virulence of tubercle bacilli are; the magnitude of proliferation in vivo, the affinity to organ or tissue, the production of proper toxic substances, the ability to compete the elimination of bacilli from the host and the secondary toxic manifestations based on the antigen-antibody reactions.
We designed a method to estimate the number of the whole bacterial population, by plate counting technique of the homogenate of whole body of mice after infection. The ability of multiplication of mycobacteria in vivo could be classified as follows:
(i) Highly virulent strain which begins to multiply immediately after the inoculation and kills mice in 10 to 14 days (bovine strain; Ravenel).
(ii) Virulent strain which multiplies after 7 days of lag phase and kills mice in 21 to 28 days (human strain; H
37Rv).
(iii) Attenuated strain which shows a weak tendence of multiplication and survives in vivo for long time without killing mice (vole daeillus and BCG).
(iv) Avirulent strain which disappears from mice bodies at the 6th to 8th week after inoculation, showing a slow and continuous becrease of number (human streptomycin-dependent strain; 18-b and human strain; HrRa), (v) Non-pathogenic mycobacteria which disappears from mice bodies at longest after 2 weeks (Mycobacterium phlei).
When virulent tubercle bacilli, strain H
37Rv, were used for infection, the death of a mouse seems to occur at whichever time the total number of bacteria in a mouse had ream ched a value of about 10
9 to 10
10. Early in the period of infection, most of the bacilli were found in the liver, whereas later in the course of the disease, the highest population of the bacilli was found in the lungs.
Being tested by the same method as above, atypical acid-fast bacilli of 11 different strains were classified into following three groups in the manner of in viv multiplication:
1) H
37Rv-type, 2) vole bacillus-type and 3) H
37Ra-type. And histological changes are also classified into three types each respectively, i. e. 1) necrosis-type, 2) pneumonia-type and 3) alveolitis-type.
Acid-fast bacilli seem to have some specific affinity to organ or tissue, thus, H
37Rv strain is largely affinitive to the lung and M, butyricum to the kidney of rabbits, M, phlei showed such pathogenic activity as causing encephalitis accompanied with paralysis or ataxia, when inoculated into auricular vein.
Virulent tubercle bacilli contain some substantial factors which are deemed to originate their virulence. In fact, intravenous injection of heat killed bacteria of virulent strain could afford to similarize the manner of in vivo multiplication of avirulent strain to that of viru lent one, And such factor exists in the particle fraction of virulent bacteria. It was made clear by use of
32P-labelled tubercle bacilli that this factor was contained in cord factor or cord factor containing lipid.
Cord factor is a proper toxic substance of tubercle bacilli. The toxicity of this substance seems to base on the inhibition of succinic dehydrogenase system and the NAD-linked dehydrogenases, such as lactic-, malic-, and α-glycerophosphoric-dehydrogenases. Cord factor possibly inhibits the biosynthesis of desamino Coenzyme A, since the lowered enzymic activities by cor
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