Inhibition of synthesis of arabinogalactan by ethambutol in Mycobacterium smegmatis.
Ethambutol at 3.0 micrograms/ml inhibited the transfer of label from D-[14C]glucose into the D-arabinose residue of arabinogalactan in whole cells of a drug-susceptible strain of Mycobacterium smegmatis. This inhibition began almost immediately after exposure of the cells to the drug. When drug-resistant M. smegmatis was used in a similar experiment, no such drug inhibition was detected. A much higher concentration of ethambutol (greater than 50 micrograms/ml) was required to show this inhibition. The drug also inhibited synthesis of arabinose-containing oligosaccharides when a cell-free enzyme system was used. These results suggest that the site of action of ethambutol is somewhere on the pathway between the conversion of D-glucose to D-arabinose and the transfer of arabinose into arabinogalactan. The primary mode of action of ethambutol appears to be inhibition of arabinogalactan synthesis.
Takayama
K
K
Mycobacteriology Research Laboratory, William S. Middleton Memorial Veterans Hospital, Madison, Wisconsin 53705.
Kilburn
J O
JO
D002473:Cell Wall / Q000187:drug effects / Q000378:metabolism; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D004977:Ethambutol / Q000494:pharmacology*; D005685:Galactans / Q000096:biosynthesis*; D005947:Glucose / Q000378:metabolism; D008351:Mannans / Q000378:metabolism; D009161:Mycobacterium / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D009844:Oligosaccharides / Q000378:metabolism; D011134:Polysaccharides / Q000378:metabolism
D005685:Galactans; D008351:Mannans; D009844:Oligosaccharides; D011134:Polysaccharides; C012189:arabinomannan; D004977:Ethambutol; D005947:Glucose; C005653:arabinogalactan