XIV. THERAPEUTIC ACTIVITY 79 



The compound does not have appreciable bacteriostatic activity against 

 microorganisms other than the tubercle bacillus.""'""'- The bacteriostatic 

 ;u'ti\-ity of PASA against M ijcobaiicrium liiberculosis is reversed by PABA 

 and to a small extent l)y saHcylic acid.'"'-'"^ PASA replaces PABA as a 

 growth factor for two mutant strains of Escherichia coli.'"^ 



The antibacterial activities determined in vitro of thirty compounds re- 

 lated in structure to PABA have been summarized by Shive.""' 



XIV. Therapeutic Activity 



LEMUEL D. WRIGHT und PETER A. TAVORMINA 



A. RICKETTSIAL DISEASES 



PABA was found to be an antirickettsial compound when Snyder et al} 

 observed that mortality in mice infected with yolk sac suspension of swine 

 typhus is markedly reduced by oral administration of PABA as a com- 

 ponent of the diet. Their findings were confirmed in mice by Andrews e^ al.- 

 Quite independenth% Greiff et al? found PABA to be rickettsiostatic in 

 typhus-infected yolk sacs and in swine typhus infection in mice. 



The effectiveness of PABA as a practical chemotherapeutic agent was 

 established by Yeomans et al.,'^ who found the drug useful in the treatment 

 of louse-borne typhus in humans. PABA was subsequently shown to be of 

 value in the treatment not only of louse-borne typhus but of other rickett- 

 sial diseases as well, including tsutsugamuchi disease (scrub typhus) and 

 Rocky Mountain spotted fever.^'^^ PABA continued to be the drug of 



lo" O. Sievers, Nord. Med. 33, 145 (1947). 



"1 J. Lehmann, Rev. gtn. sci. 54, 222 (1947) [C. A. 42, 4641 (1948)1. 



1"= E. Diczfalusy, Arkiv. Kemi, Mineral. Geol. 24B, No. 13, 1 (1947) [C. A. 42, 5506 



(1948)]. 

 '" G. P. Youmans, G. W. Raleigh, and A. S. Youmans, ./. Bacleriol. 54, 409 (1947). 

 '"^ G. Ivanovics, Proc. Sac. Exptl. Biol. Med. 70, 462 (1949). 

 '"5 D. Yegian and R. T. Long, /. Bacleriol. 61, 747 (1951). 



»»« R. J. Williams, R. E. Eakin, E. Beerstecher, Jr., and W. Shive, The Biochemistry 

 of B Vitamins, p. 481. Reinhold Publishing Corp., New York, 1950. 

 ^ J. C. Snyder, J. Maier, and C. R. Anderson, Rept. Natl. Research Council, Divis. 



Med. Sci. (Dec. 26, 1942). 

 2 C. H. Andrews, H. King, and G. Van den Ende, Biol. Rept. Natl. Inst. Med. Re- 

 search, London (1943). 

 » D. Greiff, IL Pinkerton, and V. Moragues, /. Exptl. Med. 80, 561 (1944). 



* A. Yeomans, J. C. Snyder, E. S. Murray, C. J. D. Zarafonetis, anrl R. S. Ecke, 

 /. Am. Med. Assoc. 126, 349 (1944). 



* N. A. Tierney, /. Arn. Med. Assoc. 131, 280 (1946). 



« C. J. D. Zarafonetis, J. C. Snyder, and E. S. Murray, Proc. Soc. Exptl. Biol. 

 Med. 61, 240 (1946). 



