STUDIES ON THE DRUG-FASTNESS OF RAT-BITE FEVER SPIROCHETE, <i>SPIROCHAETA MORSUS-MURIS</i>

Abstract

If mice infected with rat-bite fever spirochete, either the human or ermine strain, are repeatedly treated with a neotrepol (bismuth preparation), it is not difficult to produce the spirochete resistant to bismuth. The biological modification in the bismuth- fast strain thus produced was studied by its comparison with the original strain in virulence and chemotherapeutic biology. We carried out the present experiments with the ermine strain of Spirochaeta morsus-muris and the results obtained are summarized as follows:1. The rat-bite fever spirochete rendered resistant to neotrepol is also resistant to the other bismuth preparations, as muthanol and casbis. This neotrepol-fastness therefore may be considered as the bismuth-fastness.2. The Bi-fast strain is still resistant to bismuth after 50 passages through mice for about 2 years.3. This Bi-fastness developed in the mouse body is positively retained, if the resistant strain is transferred to the rat body.4. When mice infected with the Bi-fast strain are repeatedly treated with compounds of the other groups than bismuth preparation, the Bi-resistance occasionally disappears. For example, the Bi-resistant strain seemingly returns to the original sensitive strain after 10 treatments with neosalvarsan (1: 1000), while this result is not as clearly noticeable with silver salvarsan and germanin (Bayer 205). Trypaflavin and parafuchsin exert no influence upon this Bi-fastness.5. Between the resistant and sensitive strains, there is no obvious distinction in virulence, whenever normal mice, rats and guinea pigs are used. If mice previously splenectomized are employed, however, the Bi-fast strain shows a slightly higher virulence in animals thus treated than in mice untreated. The original spirochete does not show such a result.6. When the reticulo-eudothelial system of mice is blocked by an injection of iron oxide saccharated or Indian ink, either the blocked or normal animals, contract with the same readiness the infection with both the resistant and sensitive strains.7. The Bi-fast strain, compared with the original, was found to be more sensitive to germanin and neosalvarsan.8. Between the Bi-resistant and sensitive strains the development of germanin-fastness having been compared, the resistant spirochete remained still sensitive to germanin even after 10 applications, while the original strain became tolerant to it after 5 treatments. Such a proves clearly that the Bi-fast strain is more susceptible to germanin than the original is.9. The Bi-fast spirochete shows also an increase of resistance to the combined therapy of neotrepol and germanin, where a drug of the other group as germanin is administered with this bismuth preparation. Here it is interesting to note that the Bi-resistant strain is decidedly more susceptible to the combined of germanin and neotrepol than to the single application of germanin. Is this due to the so-called antimutative action (Morgenroth and Freund) of germanin ?10. Whenever parafuchsin, ethylviolet or tryparosan as the I substance and 1: 1000 of neosalvarsan as the II substance are used, the phenomenon (Browning and Gulbransen) is not observable in mice infected with both the Bi-fast and original strains. Here also the resistant strain shows a higher susceptibility to the combined of I and II substances than does the original strain.11. Parafuchsin (especially 1: 500, 1: 1000) being combined with 1: 500 of neosalvarsan, however, the chemotherapeutic interference tends to take place only in mice infected with the Bi-resistent strain.12. In mice whose reticulo-endothelial system is previously blocked with Indian ink, the infecting spirochete, either Bi-fast or original, shows an increased tolerance to the treatment of neosalvearsan. On the other hand, such an increase of tolerance is not detected in splenectomized mice.