S68 A THEORY OF MICROBIC VIRULENCE 



Among the toxigenic bacteria variations in virulence (toxin production) have not 

 been regularly or frequently associated with variations in other properties. The corre- 

 lation in the diphtheria group of the capacity to produce toxin and to ferment certain 

 sugars has been repeatedly emphasized and as often demonstrated to be general but 

 not invariable. The identification of toxigenic or non-toxigenic strains of this group 

 by the demonstration of barred or granular structures after special staining has been 

 found similarly untrustworthy. 



Among the non-toxigenic bacteria, the correlations of virulence with other prop- 

 erties have been more extensively and more decisively established. That capsulated 

 bacteria are generally more virulent than non-capsulated strains of the same species 

 or genus has long been known.' When, by animal passage or other treatment, viru- 

 lence is enhanced, encapsulation becomes more marked; and when, by any of nu- 

 merous devices, virulence is attenuated, encapsulation is reduced or even abolished. 

 These relations are easily demonstrated with pneumococci, streptococci, anthrax 

 bacilli, members of the Friedlander group, and with many other bacteria. Similarly, 

 it is generally found that virulent or capsulated bacteria are relatively inagglutinable 

 by immune sera and are not easily or readily phagocyted. The direct correlation 

 between virulence and encapsulation, and the inverse correlation of virulence and 

 phagocytability, is extremely common, if not invariable. 



It has been argued, and perhaps properly, that the correlation between high 

 virulence and resistance to phagocytosis (and vice versa) is really not a correlation 

 but an identity. A non-toxigenic parasite whose virulence is dependent upon the 

 invasion of tissues and fluids is virulent if it is immune to phagocytosis (and to 

 humoral antibodies), and is avirulent if susceptible. Furthermore, the identity is 

 sometimes extended to include encapsulation. The organism is virulent — it is alleged 

 — because the presence of the capsule renders it insusceptible to engulfment or diges- 

 tion by the phagocyte (or to destruction and dissolution by a bactericidal or bacterio- 

 lytic agency). 



According to other views, these correlations are incidental and not determining 

 characteristics of virulence. The real basis of virulence, it is alleged, is the production 

 and excretion by the micro-organism of endotoxins, aggressins, virulins, anaphyla- 

 toxins, etc. — metabolic products which injure the defense mechanisms of the host or 

 interfere with their action upon the bacteria. Although the significance of endotoxins 

 and aggressins has been repeatedly and effectively challenged, the role of virulins' 

 is still frequently accorded respectful mention. Virulins have been reinvestigated 

 recently in my laboratory by Miss Margaret Pittman.-' Except for a slight reduction 

 in the phagocytosis of avirulent pneumococci, extracts prepared from virulent 

 pneumococci after the methods of Rosenow were without demonstrable capacity to 

 affect virulence. The role of the acidic and alkaline metabolites, "ptomaines," pres- 

 sor substances, etc., in the mechanisms of virulence have been adequately discussed 

 in the standard textbooks and demand no treatment here. 



' Cf. the review in Zinsser, H.: Infection and Resistance (3d ed.), p. 14. New VorU, 1923. 



2 Rosenow, E. C: J . Infcrt. Dis., 4, 285. 1Q07. 



3 Piltman, M. J.: Master's disserlation. University of Chicago, 1926. 



