^-AMINOBENZOIC ACID 



substance or elective against organisms not inhibited by sulphanil- 

 amide. 



It was only natural that many attempts should have been made to 

 find an explanation of the striking antibacterial properties of sul- 

 phanilamide and its derivatives, and several plausible theories were 

 put forward. The one that received most support and the one now 

 generally accepted was based on the observation that the inhibitory 

 effect of sulphanilamide could be prevented by various substances, 

 such as peptone,'^ fractions from Streptococcus ^ and Brucella abortus ^ 

 and certain enzymes ^° and tissue extracts. ^^ D. D. Woods ^^ frac- 

 tionated the anti-sulphanilamide fraction of yeast, and found that the 

 purified substance possessed many of the properties of ^-aminobenzoic 

 acid. On testing synthetic ^-aminobenzoic acid he found that this, 

 in fact, did neutralise the antibacterial action of sulphanilamide, and 

 he therefore suggested that sulphanilamide inhibited the growth of 

 bacteria by competing with ^-aminobenzoic acid for certain enzymes 

 essential for their growth. F. R. Selbie ^^ confirmed Woods' observa- 

 tions by showing that mice succumbed to a streptococcal infection 

 when ^-aminobenzoic acid was administered simultaneously with 

 sulphanilamide. On the basis of this evidence, P. Fildes ^^ expressed 

 Wood's theory in more general terms, and suggested that ^-amino- 

 benzoic acid was an essential metabolite, although not necessarily a 

 growth factor, for all organisms that are inhibited by sulphanilamide. 



Subsequently, S. D. Rubbo and J. M. Gillespie ^^ succeeded in 

 isolating pure ^-aminobenzoic acid from yeast. They found that it 

 could be titrated against sulphanilamide by using the growth of micro- 

 organisms as the end-point, i mole antagonising 23,000 moles of sul- 

 phanilamide. Other workers ^® showed that ^-aminobenzoic acid 

 similarly antagonised the antibacterial effects of derivatives of sul- 

 phanilamide, e.g., sulphathiazole, sulphapyridine and sulphadiazine. 



Strauss et al.^'^ made a careful study of the inhibition of the sul- 

 phonamides by ^-aminobenzoic acid and found that : [a) the sul- 

 phonamides varied in the extent to which ^-aminobenzoic acid affected 

 them, the bacteriostatic action of 10 mg. % of sulphathiazole, sul- 

 phapyridine and sulphanilamide being inhibited by 0-04, 0-02 and 

 0-004 i^g- % of ^-aminobenzoic acid respectively ; (b) the addition 

 of ^-aminobenzoic acid to bacteria at different stages of growth 

 could " revive a culture in the presence of sulphapyridine at any 

 stage in the growth curve as long as there are any viable organisms " ; 

 (c) after ingestion of _^-aminobenzoic acid by humans, the urine inter- 

 fered with the action of sulphathiazole on Escherichia coli, although 

 to a smaller extent than did added ^-aminobenzoic acid of the same 

 concentration as measured colorimetrically, indicating that some 

 change, such as conjugation or oxidation, had taken place in the 



546 



