242 IMMUNO-CATALYSIS 



of bacteria are well known. A satisfactory correlation of the invasive 

 or virulent character of a microorganism with its ability to elaborate 

 a certain pertinent enzyme in vivo would seem to require the study of the 

 two factors under identical conditions. Attempts to correlate the invasive- 

 ness of a bacterium with its ability to produce hyaluronidase in vitro, 

 no doubt, fails to meet the above criterion. The constancy of optimal 

 pH, the presence of critical substances, the age of the culture, the rate 

 of the autolysis of bacteria, the stability or resistance to denaturation 

 effects, the action of proteolytic enzymes, and the presence or absence 

 of inhibitors are factors which play a significant role on the amount and 

 activity of a given enzyme produced during in vitro growth. The 

 virulence or invasive ability of organisms harvested from such an 

 environment cannot be assumed to have an unfailing correlation with 

 the activity and the amount of hyaluronidase that may or may not be 

 produced. The inclusion of the specific whole substrate in the growth 

 medium has been reported to enhance or stimulate (or protect from 

 destruction) certain bacterial enzymes, such as hyaluronidase. And 

 since the ground substance of the connective tissue is a viscous substance 

 containing, probably, hyaluronate, the in vivo environment may offer 

 the ideal condition for the maximal production of hyaluronidase and, 

 therefore, for its correlation with the invasive or virulent character of 

 the organisms. In this respect organisms, such as staphylococci, strep- 

 tococci and certain Clostridia, which make use of host's skin, rich in 

 hyaluronidase substrate, as an entrance into the body prior to spreading 

 to other sites, would seem to offer a suitable means to correlate bacterial 

 invasiveness with the ability to elaborate hyaluronidase at the site of 

 initial infection. From this point of view, as discussed below, the studies 

 of McClean, et at. (1943), and McClean and Rogers (1944) are most 

 significant. We will first discuss the results of studies on the production 

 of hyaluronidase by bacteria grown in vitro. These will be followed by 

 the presentation of the results obtained in in vivo experiments by Kass 

 and Seastone (1944) and McClean (1941) and McClean and his 

 associates (1943, 1944). 



Crowley (1944) tested 308 strains of group A streptococci for 

 hyaluronidase production. Only two serological types (types 4 and 22) 

 showed hyaluronidase activity. Of the 65 strains of groups C and G 

 streptococci tested 48 showed hyaluronidase activity. Hyaluronidase 

 producing strains were stated to be invariably non-capsulated. She failed 



