. Ciba Foundation symposium on drug resistance in micro-organisms: mechanisms of development. Drug resistance in microorganisms. 190 ROLLIN D. HOTCHKISS AND AuDREY H. EvANS shown in Fig. 2 seem confusing when it is reahzed that tur- bidity increases almost as much as in the control when 10 to 20 times the inhibitory concentration of SA is present. The explanation lies in the limited number of divisions observed in the experiment. As indicated in Fig. 3, different growth media can supply different samples and quantities of the eventual products of PAB metabolism. In addition, the cells themselv
. Ciba Foundation symposium on drug resistance in micro-organisms: mechanisms of development. Drug resistance in microorganisms. 190 ROLLIN D. HOTCHKISS AND AuDREY H. EvANS shown in Fig. 2 seem confusing when it is reahzed that tur- bidity increases almost as much as in the control when 10 to 20 times the inhibitory concentration of SA is present. The explanation lies in the limited number of divisions observed in the experiment. As indicated in Fig. 3, different growth media can supply different samples and quantities of the eventual products of PAB metabolism. In addition, the cells themselves can accumulate and later use substantial amounts of the catalytically effective product(s) of PAB, folic Environment Metabolism Measurement cSi?i;?s4Tctori-'-Cf^""i'>^p-=--o- COOH Sulfonamide inhibition. streptococcal assay TOLIC ACID -' cell substance (nucleic acid; protein) Fig. 3. Determination of inhibitory effects of sulphonamides. medium supplies non-competitive products of folic acid system - pneumococcal endogenous assay -->- turbidity acid(s). Therefore, when placed under conditions fully inhibitory to folic acid synthesis the cells nevertheless are able to complete a limited number (usually three to five) ter- minal divisions. When using such measures of growth as turbidity, one may purposely start with an initial culture heavy enough to measure. An increase of 10- to 30-fold may be possible in sulphonamide so that the measuring instru- ment may only reveal the late stages of inhibition or none at all, as in Fig. 2. It is clear, therefore, that the true ability to survive in sulphonamide is only assessed when indefinite propagation is demanded, as when single organisms are required to produce colonies. A second difficulty is the PAB-sparing effect of end-. Please note that these images are extracted from scanned page images that may have been digitally enhanced for readability - coloration and appearance of these illustrations may not perfectly rese
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