EFFECTS ON THE GROWTH OF MICROORGANISMS 267 



Little is known of the responses of bacterial infections to iodoacetate. 

 Administration of iodoacetate prolongs the life of guinea pigs given sub- 

 cutaneous inoculations of Bacillv.s anthracis, and this was attributed to an 

 inhibition of certain proteinases involved in the virulence of these bacteria 

 (Wohlfeil and Wollenberg, 1938). It has been stated that iodoacetate given 

 to tuberculous guinea pigs has no effect on the bacteria but inhibits the 

 breakdown of the infected tissue, thus reducing the spread of the infection 

 (Mauer and Kinkeldey, 1953). Combination with isoniazid suppresses dis- 

 semination of the infection better than with either substance alone. Investi- 

 gations such as those by Berry and co-workers on infections, using mal- 

 onate, would perhaps provide interesting results on the complex mechanisms 

 involved in bacterial growth, invasiveness, and host responses. 



Viruses and Bacteriophages 



It is evident that effects mediated through EM pathway inhibition must 

 be on the host cells since viruses do not possess the glycolytic enzymes, and 

 that depression of viral proliferation by this mechanism must be the result 

 of a decrease in the generation of ATP and consequent interference with 

 syntheses required for the formation of virus. On the other hand, some 

 viruses may have reactive SH groups, alkylation of which would so modify 

 virus structure as to impede duplication. Incubation of tobacco mosaic virus 

 with high concentrations of iodoacetamide (50-100 mM) at pH 8 leads to 

 partial inactivation of the virus, but under these conditions it is impossible 

 to say what groups are reacted (Anson and Stanley, 1941). The virus is 

 obviously quite resistant. Influenza virus PK-8 is also resistant since 50 mM 

 iodoacetamide at pH 7 has no effect before 8 days (Knight and Stanley, 

 1944). No direct effects on mouse pneumonia virus by 10 mM iodoacet- 

 amide were observed (Volkert and Horsfall, 1947). Larger more complex 

 viruses seem to be much more susceptible. Psittacosis virus is partially 

 inactivated by 2.5 mM iodoacetamide, but not at all by 4.5 mM iodoace- 

 tate, incubation being 1 hr at 37° (Burney and Golub, 1948). The inactiva- 

 tion of vaccinia and fowl plague viruses by SH reagents is first order at 

 0.1 mM; iodoacetamide reduces the virus titer markedly (Allison, 1962). 

 The primary attachment of the virus to the host cell and its penetration 

 are not affected, and possibly the uncoating of the virus preceding multipli- 

 cation is prevented. Allison et al. (1962) made an extensive study of the 

 susceptibility of many viruses to iodoacetamide, the viruses being exposed 

 to the inhibitor for 1 hr at 18° and pH 7.4. Certain viruses, such as vaccinia, 

 influenza A-MEL, and Newcastle, appear to be quite sensitive to iodoacet- 

 amide since 0.1 mM reduces their titer several hundredfold. On the other 

 hand, Coxsackie and Echo 7 viruses are completely resistant to 1 mM iodo- 

 acetamide. Thus there is evidence that iodoacetamide can directly modify 

 viruses to reduce their infectivity or proliferative activity, but nothing is 



