Enhancement of Pathogenicity of Human Typhoid Organisms by Mucin

Abstract

It is recognized that experimental work on typhoid fever has been handicapped by the lack of a small susceptible laboratory animal. Even with highly virulent strains of B. typhosus, several million organisms are required to kill mice when inoculated intraperitoneally. With such numbers, the fate of the animal is due not only to virulence and invasiveness but also to toxicity from products of disintegration of the organisms. Recently Norton and Dingle 1 have been able to increase the virulence of B. typhosus 20,000 times by intracerebral inoculation. By combining the typhoid organisms with mucin, as used for other organisms,2-6 their virulence for mice can be increased a million times.

The method for the preparation of mucin has been given elsewhere. 4 , 6 Twelve- to 15-hour cultures of the organisms on plain agar have been used throughout. Thirteen cultures of B. typhosus and 2 each of Paratyphoid A and B have been tested. Five B. typhosus cultures were isolated within 9 months and of these, 3 required only 10 organisms to kill while 2 required 100. One strain was 2 years old and required 1,000 organisms to kill; while the other 7 were old stock strains and all failed to kill with 100,000 organisms (the largest number tested) save one, the so-called Rejuvenated Rawlins strain, which required only 10 organisms.∗ The Paratyphoid strains were old stock cultures. Three failed to kill with 100,000 organisms, but in the fourth 100 organisms killed. This strain had been kept frozen and dried without sub-culture for years. In the case of the stock strains that failed to kill, Rough, Normal and Smooth, motile and non-motile forms were noted. All of the virulent strains were smooth and motile. Comparative tests with the same virulent strains suspended in broth and mucin showed an increase in virulence of from 100,000 to over 1,000,000 times. It will be noted that the virulence of the stock strains was not enhanced to a like degree, suggesting that a great part of their activity is due to the breaking down of the large numbers of organisms.