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(Received for publication, July 16, 1996, and in revised form, September 9, 1996)
From the The low permeability of the mycobacterial cell
wall is thought to contribute to the well known resistance of
mycobacteria to antibiotics and chemotherapeutic agents. We have used
differential scanning calorimetry to demonstrate that the high
temperature phase transition observed in purified cell walls, usually
in the 60-70 °C range, suggestive of a lipid environment of
extremely low fluidity, can also be observed in whole organisms and in
cell walls from which much of the free lipids was removed by extraction with Triton X-114. A survey of seven mycobacterial species demonstrated that this high temperature transition was a general property of these
organisms. Cell walls isolated from two Corynebacterium species, which contain much shorter corynemycolic acids, displayed a
much lower temperature transition, suggesting that the transition temperature was directly correlated to the length of mycolic acid. Methyl esters of mycolic acids were found to have a phase transition temperature that was linearly related to the amount of
trans-mycolate. Both Mycobacterium avium and
M. smegmatis responded to increasing growth temperature by
increasing the proportion of trans-mycolate and displaying
a correspondingly higher melting temperature. Whole cells of M. smegmatis grown at higher temperature allowed a less rapid influx
of two lipophilic agents, norfloxacin and chenodeoxycholate. These
results provide strong evidence that the nature of mycolic acid plays a
crucial role in determining the fluidity and permeability of
mycobacterial cell wall.
Volume 271, Number 47,
Issue of November 22, 1996
pp. 29545-29551
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.
,
Department of Molecular and Cell Biology,
University of California, Berkeley, California 94720-3206, the
§ Tuberculosis Research Unit, National Institute of Allergy
and Infectious Diseases, Rocky Mountain Laboratories, Hamilton, Montana
59840, and the ¶ Department of Microbiology, Colorado State
University, Fort Collins, Colorado 80523
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