THE DETECTION OF BACTERIAL PATHOGENICITY 227 



of the bacterial inoculum. For example, if an otherwise resistant host 

 were to be injected with a massive dose, something of the order of 500 or 

 600 mg dry weight of a particular organism, the animal might die of a 

 massive artificial toxemia or, if it survives, might carry viable bacteria for 

 long periods of time. In neither instance is this a satisfactory demonstra- 

 tion of pathogenicity. Conversely, inoculation of a few cells of a moder- 

 ately pathogenic agent, as Clostridium, perfringens, may be insufficient to 

 establish either infection or a lethal toxemia. For these reasons, when 

 attempting to measure pathogenicity, it is well to inject a high (several 

 million) and low (200-300) number of bacteria in separate sets of test 

 animals. In this manner the potential invasiveness of the organism is 

 more likely to be demonstrable and the host's phagocytic resistance 

 mechanisms will not be overwhelmed through the sheer mass of foreign 

 inoculum. 



6. Pathogenic bacterial populations are a collection of dishomogeneous 

 microorganisms whose total invasive capacity is labile and subject to 

 great variation. Both the number of cells and their virulence are mark- 

 edly affected by the external environment. Prolonged cultivation may, 

 and usually does, lead to the development of a strain whose mutant 

 composition differs markedly from the original isolate. The relationship 

 of pathogenicity to M, S, R, or G colony types and to the morphology, 

 size or age of the cell may have to be determined for each culture. With 

 some organisms, e.g., Salmonella typhosa and Corynehacterium diphtheriae, 

 the smooth colony type is the most pathogenic, whereas the mucoid 

 phase of Diplococcus pneumoniae and the rough phase of other organisms, 

 such as Bacillus anthracis, are the most pathogenic. Unfortunately the 

 colonial morphology of cell mutants is not always associated with viru- 

 lence in the same fashion. Some species, such as Malleomyces, may be 

 lethal in the rough, smooth, or mucoid stages, or virulence can change 

 markedly without any alteration in colonial or cell morphology. For 

 each specific microorganism the worker should familiarize himself with 

 the range of variation and with associated states of pathogenicity. This 

 is absolutely essential for intelligent pathogenicity studies. 



In certain instances, as in the case of the meningococci, an organism 

 which is pathogenic for man is only weakly so or avirulent for animals. 

 By inoculating the bacteria in combination with certain adjuvants, as 

 starch or mucin, it is possible to block phagocytosis in the host tempo- 

 rarily, thus permitting the original inoculum to multiply and eventually 

 overwhelm the animal's resistance. Such artificially enhanced virulence 

 is, strictly speaking, not within the province of this section, since it does 

 not necessarily reflect an inherent pathogenicity of the organism but 

 rather the ability of the adjuvant to blockade host defenses. On the 

 other hand it may occasionally be necessary to use adjuvants with old 



