66 METABOLISM 



A nutrient may therefore be defined as a substance that is essential either for 

 minimal growth, perhaps under restricted conditions, of an organism trained to be 

 as unexacting as possible, or for optimal growth. The studies of Mueller (1940), 

 for example, on the nutritional requirements of the diphtheria bacillus, have 

 been conducted on the basis of optimal growth, which he defines as the best attain- 

 able upon empirically devised media. In the first case, a medium is sought that 

 will promote the growth of at least one of the cells originally inoculated, and the 

 production of a trained culture is most probably due to selection of cells with 

 the greatest synthetic powers. In the second case, not only the reproduction, 

 but the ready and profuse growth, of all the viable cells of the inoculum is aimed 

 at. The substances required for this purpose, over and above the minimal require- 

 ments, are generally called stimulants of growth, though Lwoff (1938) in his review 

 of growth factors for micro-organisms distinguishes stimulants from " starting 

 factors," which are substances essential for the growth of an organism at the 

 commencement of its training, but which are dispensed with by the trained organism. 

 In some cases, however, the addition of a starting factor to the minimal medium 

 enhances growth, and the distinction breaks down. A true stimulant presumably 

 acts by supplying in abundance an essential metaboUte that the bacterium itself 

 synthesizes only at a relatively slow rate. 



With these reservations in mind, we may note that for many heterotrophic bacteria 

 in Stages 3 and 4, the essential nutrients, carbohydrate, nitrogenous, and growth factors 

 (vitamins), have been defined. Among bacteria pathogenic for man we have already 

 cited Staph, aureus and C. diphtherice, and to these we may add Str. hcemolyticus (see 

 Mcllwain 1940) ; Group D streptococci (Woolley and Hutchings 1940) ; Sir. salivarius 

 (Smiley, Niven and Sherman 1943) ; Str. lactis (Niven 1944), and Str. fcecalis (Niven 

 and Sherman 1944) ; Myco. tuberculosis (see, for example, Lockemann 1942) ; N. menin- 

 gitidis (Frantz 1942) ; N. gonorrhoece (Gould, Kane and Mueller 1944) ; Br. abortus, meli- 

 tensis and suis (Koser, Breslove and Dorfman 1941, Koser and Wright 1942, McCullough 

 and Dick 1942) ; and certain members of the Salmonella group (Johnson and Rettger 

 1943). The requirements of different strains of organisms belonging to the same species 

 may vary widely, some having greater, some lesser synthetic powers than the strain for 

 which the essential nutrients were fixst defined. There is a large number of heterotrophic 

 bacterial species for which the essential nutrients are as yet only partly defined ; for 

 the most part the carbohydrate and amino-acid requirements are readily estabUshed. 

 For example, the main body of essential nutrients is defiiaed for certain Clostridia (Elberg 

 and Meyer 1939) ; pneumococcus Type III (Badger 1944) ; Br. tularensis (Tamura and 

 Gibby 1943) ; certain pasteurellse (Berkman 1942) ; and CI. tetani (Mueller and MiUer 

 1942, Feeney, Mueller and MiUer 1943, Pickett, 1943). These organisms are presumably 

 in Stage 4, since the remaining unidentified factors are usually active in low concentrations 

 and are probably accessory growth factors. 



The Vitamin Requirements of Bacteria. 



In addition to foodstuffs needed for energy and synthesis, many of the hetero- 

 trophic bacteria require vitamins. A vitamin or accessory growth factor is an 

 essential nutrient active in concentrations so small that it is unhkely to act as 

 an important source of either carbon, nitrogen or energy. Such substances range 

 from inorganic ions to complex organic substances like thiamin or riboflavine, 

 and the majority so far described appear to be in some way connected with the 

 function or the structure of enzyme-co-enzyme systems of the organism. It is 

 customary to limit the term vitamin to organic compounds, but it should be noted 

 that, on the ground of their activity in low concentrations, many inorganic sub- 

 stances have equal claim to the title. In certain conditions, for example, the 



