520 THE BIOCHEMISTRY OF B VITAMINS 



Shigella sonnei. 388 The synthesis of anti-sulfonamides occurs in both the 

 presence and the absence of sulfonamides. 371, 373 The sulfonamide in- 

 hibitors may be restricted to the cells or released into the medium. 340 

 Although the inhibitor in most cases noted is p-aminobenzoic acid, some 

 inhibitors exhibit different properties and presumably are not p-amino- 

 benzoic acid. 340 



Conversely, in experiments with certain resistant strains of Shigella 

 paradysenteriae Sonne, 18 Diplococcus pneumoniae Type I, 18 and Sta- 

 phylococcus aureus 3 ^ 1 there was no demonstrable increase in synthesis 

 of p-aminobenzoic acid, 18 and for certain resistant strains of Neisseria 

 gonorrheae increased synthesis of p-aminobenzoic acid was insufficient to 

 account entirely for such resistance. 355 A sulfathiazole-resistant strain of 

 staphylococci with no increased production of an anti-sulfonamide was 

 found to require smaller amounts of p-aminobenzoic acid for reversal of 

 sulfonamides than the parent strain. 389 



Ivanovics 127 compared the minimum inhibitory concentrations of sul- 

 famethylthiazole and the inhibition indices obtained with resistant and 

 parent strains of Staphylococcus aureus. The data listed in Table 9 

 indicate that the resistance of this organism can be accounted for by 

 increased production of p-aminobenzoic acid or a related sulfonamide 

 antagonist, or by more efficient utilization of p-aminobenzoic acid, or by 

 a combination of the two mechanisms. The former mechanism is char- 

 acterized by an increased minimum inhibitory concentration for the 

 resistant organisms, but does not involve a change in the inhibition index. 

 More efficient utilization of p-aminobenzoic acid results in an increased 

 inhibition index. 



Differences Between Resistant and Parent Strains. Although the virul- 

 ence of an organism is usually unchanged in the acquisition of sulfonamide 

 resistance, 206 - 331, 35S - 389> 392 in some cases contrary observations have been 

 made. 336 - 337> 348 - 393 Certain strains of Shigella sonnei 337 and /^-hemolytic 

 streptococci 348 became nonvirulent on becoming resistant to sulfonamides. 

 Meningococci which became resistant to sulfanilamide lost their virulence, 

 while those resistant to sulfapyridine remained virulent. 393 A sulfonamide- 

 resistant strain of gonococcus lost its pathogenicity, and it could not be 

 restored by treatment with p-aminobenzoic acid. 120 



More often than not, the morphology of the resistant strain remains the 

 same as that of the parent strain; 266, 338 - 350 ' 363, 367 however, changes have 

 been noticed in some cases. The more resistant strains of staphylococci 

 studied produced a nonfat-soluble yellow pigment in the presence of 

 sulfonamides. 372 However, strains which were not as highly resistant did 

 not produce this pigment. It is suggested that this pigment may be derived 

 from p-aminobenzoic acid. 



