68 P-AMINOBENZOIC ACID 



sus^^ methods for PABA determination. Increased synthesis of PABA by 

 sulfonamide-resistant strains of staphylococci was noted by Hoiisewright 

 and Koser,^'* using the Clostridium aceiobutylicum assay. Increased PABA 

 production was subsequently found by Landy and Gerstung^^' ^^ to be 

 associated with the development of sulfonamide resistance in Neisseria 

 gonorrhoeae. Less conclusive evidence that PABA synthesis is correlated 

 directly with sulfonamide resistance in Diplococcus 'pneumoniae,^- ^''- ^^ 

 strains of Clostridia, ^^ Brucella paramelitensis,-'^ and Shigella sonnei^'^ has 

 been presented. On the other hand, Landy et al}^ did not find increased 

 PABA synthesis associated with sulfonamide resistance in strains of Es- 

 cherichia coli, Vibrio cholcrae, Shigella dysenferiae, or Diplococcus pneu- 

 moniae, and Housewright and Koser'* concluded as a result of microbio- 

 logical assays with Clostridium acetohutylicum that sulfonamide resistance in 

 Shigella paradysenteriae and Diplococcus pneumoniae is not associated with 

 increased PABA production. It must be concluded that with certain species 

 of bacteria, particularly the staphylococci, sulfonamide resistance is ex- 

 plainable in terms of increased PABA synthesis, but that in other species, 

 for example, Escherichia coli, sulfonamide resistance is not associated with 

 the same phenomenon. 



Of equal interest with respect to the functions of PABA in metabolism 

 is a consideration of the reversal of sulfonamide action by compounds 

 unrelated to PABA in structure. 



Soon after Woods observed that PABA reverses sulfonamide action, it 

 Avas observed that methionine exhibits a similar activity .-^-^ Adenine or 

 hypoxanthine is reportedly as active as PABA in negating the effect of 

 sulfanilamide against Streptococcus hemolyticus infection in mice,-^ and 

 various purines reverse the effect of sulfonamides on lactic acid bacteria.'-^ 

 More recently the sulfonamide-reversing activities of thymine,-'^"-^ folic 



13 J. C. Lewis, J. Biol. Chem. 146, 441 (1942). 



1^ R. D. Housewright and S. A. Koser, /. Infectious Diseases 75, 113 (1944). 



15 M. Landy and R. B. Gerstung, J. Bacteriol. 47, 448 (1944). 



16 M. Landy and R. B. Gerstung, J. Immunol. 51, 269 (1945). 

 " A. Zimmerman and R. M. Pike, J. Bacteriol. 45, 522 (1943). 

 i» G. S. Mirick, /. Bacteriol. 45, 66 (1943). 



13 G. B. Reed, J. H. Orr, and R. W. Reed, J. Bacteriol. 48, 233 (1944). 

 2» H. N. Green and F. Bielschowsky, Brit. J. Exptl. Pathol. 23, 1 (1942). 



21 E. A. Bliss and P. IL Long, Bull. Jolins Hoptcins Hosp. 69, 14 (1941). 



22 J. S. Harris, and H. I. Kohn J. Pfiarmacol. Exptl. Tluiap. 73, 383 (1941). 

 2» J. S. Harris and H. I. Kohn, ./. Biol. Chem. 141, 989 (1941). 



2< H. I. Kohn and J. S. ILarris, ./. Pliarmacol. Exptl. Thcrap. 77, 1 (1943). 



25 G. J. Martin and C. V. Fisher, J. Biol. Chem. 144, 289 (1942). 



26 E. E. Snell and H. K. Mitchell, Arch. Biochem. 1, 93 (1943). 



2' J. O. Lampen and M. J. Jones, /. Biol. Chem. 170, 133 (1947). 



28 J. O. Lampen and M. J. Jones, J. Biol. Chem.. 166, 435 (1946). 



29 K. C. Winkler and P. G. deHaan, Arch. Biochem. 18, 97 (1948). 



