TOLERANCE AND RESISTANCE 449 



general exclusion of cations from the cell. As Horsfall (174) points out, 

 an organism producing metabolic acids may be less sensitive to a toxi- 

 cant which must compete with hydrogen ion for its site of action. 



Fungi may also be "trained," by serial culture in media containing 

 low doses of a toxicant, to tolerate a normally inhibitory concentration. 

 Such adaptation has been demonstrated to arsenite (157), borax (205), 

 fluoride (222), and copper (186, 195); other reports are cited by Leben 

 etal. (217) and Horsfall (174). Such adapted strains and strains which 

 appear spontaneously in culture are usually unstable and lose their 

 resistance on subculture in toxicant-free media (158, 195). Spon- 

 taneously arising sectors of Fusarium caeruleum appear in plates ex- 

 posed to the vapor of 2,3,5,6-tetrachloronitrobenzene, and these variants 

 are somewhat less sensitive to the poison than is the parent strain 

 (263); they are, however, almost equally sensitive — by rather inexact 

 criteria — to 2,3,4,5-tetrachloronitrobenzene (47). 



Genetic analysis has been performed only infrequently on resistant 

 strains of fungi. Resistance to indole toxicity in Neurospora crassa 

 (77) and to acriflavine in Aspergillus nidulans (355) is genetically con- 

 trolled. This is in line with the usual experience in studies on bacteria 

 and yeast (85, 216, 371). Copper-adapted yeast is reported to contain 

 a ribonucleic acid which can be transmitted to, and which confers 

 copper resistance on, normal unadapted yeast cells (293). 



Physiological mechanisms of acquired tolerance are possibly of di- 

 verse types. Work on the resistance of trypanosomes to arsenicals sug- 

 gests that resistant strains are less permeable to the drug (38), possibly 

 by virtue of an altered distribution of surface charges (366). Fluoride 

 tolerance in clones of Propionibacterium pentosaceum appears also to 

 be a permeability phenomenon (427). Other mechanisms are, however, 

 possible: an antimycin-resistant variant of Venturia inaequalis probably 

 lacks the normal respiratory system sensitive to the antibiotic (219). 



Detoxification of fungicidal agents has been observed and is, of 

 course, a potential mechanism of resistance. Methylation of selenium, 

 tellurium, and arsenic (Chapter 6) conceivably fits in this category. 

 The effects of cycloheximide on both spore germination and respira- 

 tion decline with time, indicating an inactivation (431, 440). Oxida- 

 tive processes have been suggested as the basis for resistance to phenols 

 and quinones (200, 347); ^-oxidation of a fatty acid side chain or hy- 

 droxylation of a ring in some instances causes detoxification (54, 57). 

 Other possible detoxification mechanisms are reviewed by Gottlieb 

 (134); it seems likely that the most common is the complexing of toxic 

 metals by chelate-forming metabolites such as amino acids and hydroxy 

 acids. 



