THE VITAMIN REQUIREMENTS OF BACTERIA 67 



toxin production by C. diphtherue is maximal with an optimal concentration of 

 iron as low as 2-8 X 10~^ M (Pappenheimer and Johnson 1936), and maximal 

 toxin production by CI. tetani is similarly conditioned (Mueller et al. 1943). 



It is impossible to review the relevant literature of the organic accessory growth 

 factors here ; summaries of recent work will be found in the reviews of Lwoff 



(1938) and Koser and Saunders (1938). In recent years, the identification and 

 ])urification of many bacterial growth factors makes it possible to assign to them 

 the role of vitamin. As noted above, tryptophan is essential for Salm. typhi, 

 whose needs are satisfied by a concentration of 0-00064 per cent., if an alternative 

 source of nitrogen is supplied for the synthesis of protoplasm. Among other 

 amino-acids we may note that cysteine is an essential accessory growth factor 

 for Staph, aureus, being active in concentrations of less than 10~® M, though less 

 complex S-compounds can replace it in a defined medium (Fildes and Richardson 

 1937), and glutathione is similarly essential for N. gonorrhoeoB (Gould 1944) ; /^-alanine 

 is a growth factor for C. diphfherm (Mueller and Cohen 1937), though the organism 

 is able to produce it from Z-carnosine (Mueller 1938). In C. diphtlierice /^-alanine 

 may be the precursor of pantothenic acid ; but Evans, Handley and Happold 



(1939) found certain gravis strains of C. diphtherice which needed both /9-alanine 

 and pantothenic acid. Pantothenic acid is apparently essential for certain strepto- 

 cocci (Mcllwain 1939, 1940, Woolley and Hutchings 1940, Schuman and Farrell 

 1941), lactic-acid bacteria (Snell, Strong and Peterson 1939), Brucella abortus 

 (Koser, Breslove and Dorfman 1941), Pr. morgani (Dorfman, Berkman and Koser 

 1942) and Sh.flexneri (Weil and Black 1944). Glutamine, which can be synthesized 

 by the cocci from glutamic acid, is required by Str. haimolyticus (Fildes and Glad- 

 stone 1939, Mcllwain, Fildes, Gladstone and Knight 1939) ; it accelerates the 

 growth of a large number of organisms. Of the recognized animal vitamins, 

 thiamin was first recognized as a growth stimulant for bacteria by Tatum, Wood 

 and Peterson (1936) working with the propionic acid bacteria. Staph, aureus, 

 which also needs thiamin as an essential metabolite, can synthesize it from pyri- 

 midine and thiazole (Knight 1937, Knight and Mcllwain 1938). Thiamin, the 

 phosphate of which acts as a co-enzyme in carboxylase systems, probably plays 

 a fundamental metabolic role in all micro-organisms (see, for example, Quastel 

 and Webley 1941, 1942), those for which it is not an essential nutrient being able 

 to synthesize it. Some dysentery bacilli, for example, apparently synthesize 

 thiamin in a defined medium containing nicotinic acid (Dorfman, Koser, Reames, 

 Swingle and Saunders 1939). 



The role of nicotinic acid has been studied extensively. It is an essential 

 nutrient of Staphylococcus (Knight 1937, Holiday 1937) ; C. diphtherias (Mueller 

 1937), some dysentery bacilli (Koser, Dorfman and Saunders 1940) ; Proteus (Fildes 

 1938, Pelczar and Porter 1940) ; Brucella (Koser, Breslove and Dorfman 1941) ; 

 and Hcem. pertussis (Hornibrook 1940) ; though, as with other essential nutrients, 

 not all strains of a given species require it. The significance of nicotinic acid 

 Ues in its relationshij) with co-enzyme I and co-enzyme II, which are respectively 

 diphosphopyridine nucleotide and triphosphopyridine nucleotide. It is supposed 

 that nicotinic acid, or nicotinamide, is synthesized into co-enzyme I by organisms 

 that cannot themselves synthesize the pyridine ring. As we have seen, co- enzyme I 

 is essential in certain dehydrogenase systems. 



Hcem. injluenzcB and Hcem. piara-injIuenzcB have even more restricted synthetic 

 powers. Hcem. para-influenzce requires co-enzyme I already synthesized for many 



