162 BACTERIOLOGICAL CHEMISTRY 



that trypanosomes became resistant to dyes and to 

 arsenic compounds. He showed that such organisms 

 no longer took up the arsenical drug, or were not stained 

 by the dye as were susceptible organisms. He explained 

 this as being due to loss of affinity of the specific receptor 

 in the organism for the drug. Trypanosomes which were 

 resistant to atoxyl were also resistant to (and unstained 

 by) dyes of the acridine, oxazine, and thiazine series but 

 not to those of the trypan-blue type nor to those of the 

 triphenylmethane series. Ehrlich noted that although 

 trypanosomes might be resistant to atoxyl or tryparsamide 

 they were not resistant to arsenophenyl glycine. It has 

 since been shown that tryparsamide resistant organisms 

 are not resistant to phenylarsenoxide or derivatives of it 

 containing carboxyl groups and that they take up the 

 compounds in the same way as non-resistant strains. 

 It is considered that the active compounds are either 

 readily water soluble or lipoid soluble and therefore 

 easily penetrate the parasite. Trypanosomes may con- 

 tain up to 60 per cent, of lipoid substances. The lethal 

 arsenic atom can then come into contact with the suscep- 

 tible groups in the organism and cause its death. The 

 arsenicals or dyes to which the organism is resistant 

 fail to act because they are not taken into the organism 

 or get held up on some non-vital structure. Arsenoxides 

 react very readily with sulphydryl groups and may kill 

 the organism by inhibiting essential enzymes which 

 contain SH groups, in the same way as mercury does. 



Strains of pneumococcus become resistant to sulpha- 

 pyridine if the dosage of the drug used for treatment 

 has been inadequate. They can also be produced in 

 vitro by growing the organism in media containing 

 gradually increasing amounts of sulphapyridine. Such 

 resistant organisms have the same morphology, virulence 

 and immunological properties as the parent strains. 

 Usually a bacterium which has become resistant to one 

 of the sulphonamide drugs is also resistant to other 



