Altered expression profile of the surface glycopeptidolipids in drug-resistant clinical isolates of Mycobacterium avium complex

Members of the Mycobacterium avium complex are the most frequently encounte red opportunistic bacterial pathogens among patients in the advanced stage of AIDS. Two clinical isolates of the same strain, numbers 397 and 417, wer e obtained from an AIDS patient with disseminated M. avium complex infectio n before and after treatment with a regimen of clarithromycin and ethambuto l, To identify the biochemical consequence of drug treatment, the expressio n and chemical composition of their major cell wall constituents, the arabi nogalactan, lipoarabinomannan, and the surface glycopeptidolipids (GPL), we re critically examined. Through thin layer chromatography, mass spectrometr y, and chemical analysis, it was found that the GPL expression profiles dif fer significantly in that several apolar GPLs were overexpressed in the cli nically resistant 417 isolate at the expense of the serotype 1 polar GPL, w hich was the single predominant band in the ethambutol-susceptible 397 isol ate. Thus, instead of additional rhamnosylation on the 6-deoxytalose (6-dTa l) appendage to give the serotype 1-specific disaccharide hapten, the accum ulation of this nonextended apolar GPL probably provided more precursor sub strate available for further nonsaccharide substitutions including a higher degree of O-methylation to give 3-O-Me-6-dTal and the unusual 4-O-sulfatio n on 6-dTal. Further data showed that this alteration effectively neutraliz ed ethambutol, which is known to inhibit arabinan synthesis. Thus, in contr ast with derived Emb-resistant mutants of Mycobacterium smegmatis or Mycoba cterium tuberculosis, which are devoid of a surface GPL layer, the lipoarab inomannan from resistant 417 isolate grown in the presence of this drug was not apparently truncated.