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J Biol Chem, Vol. 274, Issue 14, 9778-9785, April 2, 1999
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From the § Department of Microbiology, Colorado State
University, Fort Collins, Colorado 80523 and the
Members of the Mycobacterium avium
complex are the most frequently encountered opportunistic bacterial
pathogens among patients in the advanced stage of AIDS. Two clinical
isolates of the same strain, numbers 397 and 417, were obtained from an
AIDS patient with disseminated M. avium complex infection
before and after treatment with a regimen of clarithromycin and
ethambutol. To identify the biochemical consequence of drug treatment,
the expression and chemical composition of their major cell wall
constituents, the arabinogalactan, lipoarabinomannan, and the surface
glycopeptidolipids (GPL), were critically examined. Through thin layer
chromatography, mass spectrometry, and chemical analysis, it was found
that the GPL expression profiles differ significantly in that several
apolar GPLs were overexpressed in the clinically resistant 417 isolate at the expense of the serotype 1 polar GPL, which was the single predominant band in the ethambutol-susceptible 397 isolate. Thus, instead of additional rhamnosylation on the 6-deoxytalose (6-dTal) appendage to give the serotype 1-specific disaccharide hapten, the
accumulation of this nonextended apolar GPL probably provided more
precursor substrate available for further nonsaccharide substitutions including a higher degree of O-methylation to give
3-O-Me-6-dTal and the unusual 4-O-sulfation on
6-dTal. Further data showed that this alteration effectively
neutralized ethambutol, which is known to inhibit arabinan synthesis.
Thus, in contrast with derived Emb-resistant mutants of
Mycobacterium smegmatis or Mycobacterium tuberculosis, which are devoid of a surface GPL layer, the
lipoarabinomannan from resistant 417 isolate grown in the presence of
this drug was not apparently truncated.
Institute of Biological Chemistry, Academia Sinica,
Nankang, Taipei 115, Taiwan, Republic of China
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