nelson: screening methods in microbiology 323 



the prevalence of organisms showing activity, most of them too 

 weak to identify further or consisting of known antibiotic com- 

 plexes (109). It is difficult to specify the exact number of known 

 antibiotics due to incomplete chemical characterization, over- 

 lapping families, and use of different names for the same 

 substance (100). 



Either an extensive or an intensive approach may be used to 

 increase the effectiveness of the screen. A more extensive program 

 would increase the combination of isolates, media, conditions, and 

 tests, usually by an increase at the input end, and the number of new 

 cultures tested. This number is already large, 20,000 per year in one 

 company's program, and the recovery of new clinically useful anti- 

 biotics is low — 3 in 10 years (74). More extensive testing of new 

 isolates may not be effective if the same organisms are merely being 

 encountered more often. This suspicion is supported by the increas- 

 ingly frequent recovery of the same antibiotic types. 



An increase in the variety of media used for fermentation may 

 yield more active isolates. The effectiveness of a given medium may 

 not be due to specific precursors but to the lack of inhibiting sub- 

 stances. However, the effect of a medium is usually quantitative and 

 the variety of media is probably not as great as the variety of organ- 

 isms. Detection of activity depends upon inhibition or killing of 

 sensitive bacteria, but more subtle effects on cell metabolism may be 

 used to screen for useful metabolites that no longer fulfill the strict 

 definition of antibiotic. No changes in media, conditions of fermenta- 

 tion, or methods of detection can be expected to replace extensive 

 testing of many different microorganisms. 



The intensive approach depends upon concentrating effort on 

 different groups of microorganisms. Elective culture methods are 

 often proposed to isolate one group of microorganisms from a mixed 

 collection in their natural habitat. Difficulties encountered here are, 

 first, elective culture methods are designed to recover a single type 

 of organism rather than all members of its physiological group, and, 

 second, such methods depend upon the selective use and not produc- 

 tion of a metabolite. Thus, it is possible to isolate one or a few 

 actinomycetes but not all actinomycetes by repetitive passage through 

 appropriate media favoring actinomycete growth, without a pref- 

 erential selection of antibiotic-producing types, however. 



