I. S. FALK 567 



TOXIGENICITY AND INVASIVENESS 



Because the dynamics of bacterial virulence still remain essentially obscure, 

 there is no general agreement among writers on this subject as to the scope, the na- 

 ture, or even the precise implications of the term "virulence." It is often recognized 

 that the capacity to produce specific toxins, to show invasiveness, avidity to fix and 

 localize on specific tissues, and capacity to necrotize are or may be distinct phe- 

 , nomena, and that it is often necessary to distinguish among them in attempting to 

 characterize the virulence of a specific parasite for a particular host. 



Virulent diphtheria or tetanus bacilli are notably lacking in high invasive prop- 

 erties. The damage they do in a host is nearly completely due to the specific toxins 

 they excrete. In such cases "virulence" is approximately coterminal with "toxigcn- 

 icity." The diphtheria bacillus that lacks the capacity to produce toxin is commonly 

 called "avirulent,"^ and some recent experiments by CrowelP indicate that toxigenic 

 capacities are genetically determined. With such organisms as Clostridium wclchii 

 or the scarlet fever streptococci, not only toxigenicity, but invasiveness and necrotiz- 

 ing capacities, determine pathogenicity. 



In recent years it has been possible to demonstrate toxin production by several 

 groups of pathogenic bacteria which formerly had been supposed to lack toxigenicity. 

 It may be that ultimately it will be established that all bacterial virulence is de- 

 pendent upon toxigenicity and that the failure of earlier workers to demonstrate 

 toxin production by this or that microbe was due to the inadequacy of the in vitro 

 methods used. But certainly we must say at the present time that the virulence of 

 most pathogenic organisms has not been resolved into toxigenicity. Nor is there any 

 general hypothesis as to the mechanism of virulence when toxin is not demonstrable. 

 On the basis of current theories, it is not easy to explain why a mouse dies some hours 

 after the injection of a few anthrax bacilli, or a rat some days after the introduction 

 of pathogenic trypanosomes. Neither is it known that these micro-organisms produce 

 specific toxins in vivo, nor is immunity against these parasites apparently associated 

 with anything like an antitoxic mechanism. The only easily demonstrable protective 

 mechanism against anthrax bacilli is associated with an enhanced phagocytic ca- 

 pacity of certain fixed tissue and wandering cells. And immunity against trypano- 

 somes may be associated chiefly with the development of trypanoly tic and anti-repro- 

 ducing properties in body fluids. 



RELATION OE VIRULENCE TO OTHER CHARACTERISTICS 



Virulence is an expression and a consequence of certain fundamental properties 

 of a parasite in the body of a host. Whether or not it is dependent upon toxin pro- 

 duction, the basis for virulence lies in the metabolism of the organism. Hence, it is 

 not surprising that many investigators have called attention repeatedly to the cor- 

 related occurrence of virulence and of other characteristic properties that are similar- 

 ly associated with metabolism and specific chemical and physical composition. 



" That this is not entirely accurate, however, may be evidenced by the fact that some cases of 

 so-called "malignant diphtheria" appear to be refractory to antitoxin treatment and that a guinea 

 pig may die after an injection of washed suspensions of non-toxigenic diphtheria bacilli even though 

 a large dose of antitoxin has been injected before or after the injection. 



^ Crowell, M. J.: /. Bad., 11, 65. 1926. 



