PERMEABILITY OF MYCOBACTERIAL CELL ENVELOPES TO STEROLS - PEPTIDOGLYCAN AS THE DIFFUSION BARRIER

Vancomycin, an inhibitor of peptidoglycan synthesis, depressed the gro wth of Mycobacterium sp. NRRL B 3805 and MB 3683, but not the beta-sit osterol side chain degradation and androstane derivatives accumulation . As a result, the specific activity (products formed/cell weight unit x h) increased threefold in the peptidoglycan-deficient cells, indica ting faster crossing of the sterol through the cell water barrier. Cel l wall preparations: crude cell wall (CCW), purified cell wall (PCW), and peptidoglycan - enriched PCW - residue (PEPCW) were obtained and a nalysed in order to find a relationship between the vancomycin - induc ed chemical changes and the permeation rate of the sterol. The amounts of CCW, PCW and PEPCW, produced from 8 g lyophilised control cells we re 445, 170 and 28 mg respectively. The respective figures were 176, 6 1, and 4.8 mg for vancomycin - treated cells. In addition to the lower content of the rigid layer, a distinct shift in the molar ratios of t he peptidoglycan constituents: alanine, glutamic, diaminopimelic and m uramic acids, and glucosamine was observed under the action of the mur ein inhibitor. The most significant change was that of muramic acid: d iaminopimelic acid molar ratio, the compounds which are markers of gly can strands and tetrapeptides, respectively. In control cells it was a pproximately 1:1, and increased to 1.34-1.43:1 in the compared prepara tion, which indicated a marked decrease in the tetrapeptide moieties c rosslinking the main glycan strands. Together with the general lower c ontent of murein, this modification may be responsible for the enhance d sterol permeation through the cell wall.