The reversal of PABA of sulfonamide inhibition of the viruses of lymphogranuloma venereum and mouse pneumonitis.

The antagonism of para-aminobenzoic acid (PABA) to the chemotherapeutic action of sulfonamides in vitro and in vivo has long been established by various workers (McCarty, 1941; Selbie, 1940; Thomas and Dingle, 1942; Woods, 1940). The studies of Woods and Fildes (Fildes, 1940; Woods, 1940; Woods and Fildes, 1940) provided, furthermore, a hypothetical picture of the metabolism of bacteria, based on the competitive antagonism of these two chemicals. The antagonism has also been extended to a sulfonamide-susceptible fungus by Dimond (1941) and malaria parasites by Seeler et al. (1943). The discovery of the chemotherapeutic action of sulfonamides on the lumphogranuloma venereum (LGV) virus (Felton et al., 1943; Findlay, 1940a,b; MacCallum and Findlay, 1938; McKee et al., 1942; Rodaniche, 1942) has led workers to investigate whether this antagonistic phenomenon ofPABA and the sulfonamides could be applied to this sulfonamide-susceptible virus (Findlay, 1940; Rodaniche, 1942; Seeler et al., 1943). However, the work was controversial. Findlay (1940), feeding 10 mg sulfanilamide and 10 mg PABA suspended in gum acacia to mice, found that PABA antagonized the chemotherapeutic action of sulfanilamide for the LGV virus injected intracerebrally. His finding was based on the development of symptoms and the death rate in mice. In contrast to Findlay's finding, Seeler et al. (1943), using a diet containing 0.3 per cent, 0.03 per cent sulfanilamide and 0.3 per cent PABA, respectively, in one experiment, and 0.03 per cent sulfamethyldiazine and 0.3 per cent PABA in another, found that PABA showed no antagonistic action in mice that had previously been infected by the intracerebral route with their strain of the LVG virus. Their finding was based on the percentage of survivors 28 days after the infection. Rodaniche (1943) fed a diet containing 2 per cent sulfathiazole and 0.5 per cent PABA to intracerebrally infected mice and found no evidence of reversal at this ratio. However, when he used an equal amount of the two chemicals together, he found that the PABA exerted some antagonistic action. After the discovery that the 6BC strain of the psittacosis virus was susceptible to sulfadiazine (Early and Morgan, 1946a,b), Morgan (1948a,b) found that PABA definitely antagonized the chemotherapeutic action of sulfadiazine on this virus in eggs and that the chemotherapeutic action of the sulfadiazine was also reversed by pteroic acid and pteroylglutamic acid. He postulated that sulfadiazine prevented the growth of the 6BC strain of psittacosis virus by interfering with its use of the PABA in the synthesis of pteroylglutamic acid.