Relationship between lipid composition and antibiotic-resistance to isoniazid, streptomycin, p-aminosalicylic acid, ethambutol, rifampicin in mycobacteria

Abstract

The content of neutral lipids, peptido-glycolipids and phospholipids, separated by solvent extractions and TLC, was investigated and compared in various strains of Mycobacterium tuberculosis and in Mycobacterium avium. The examined strains could be divided into two groups: (i) those possessing a stable INH-resistance with a chromosomal location for the resistance genes, in which the content of total lipids and the distribution of lipid subfractions were modified with respect to the control strain H37Rv; (ii) those strains, such as the mutants resistant to streptomycin (Sm), ethambutol (EM), p-aminosalicylic acid (PAS) and rifampicin (R/AMP), uncorrelated drugs with different genetic location of the antibiotic-resistance, in which a disturbance of the lipid metabolism does not appeared to be significant. TLC and chemical analysis of INH-mutants suggested that the decrease of the cell lipids was associated with the peptidoglyco-phospholipid fraction, while the neutral lipids were characterized by a most elevated amount of both menaquinone-9 and free fatty acids, and by comparable levels of both glycerides and total fatty acids with respect to the sensitive strain. In the pattern of fatty acid shorter than C26 of all the fractions studied, no significant differences were observed between the H37Rv strain and the other resistant strains, including the M. avium. In the course of the lipid analysis no unusual phospholipids in addition to CL, PE and phosphatidylinositol-oligo-mannoside (PIM) were detected. Reasoning in a speculative way, the dramatic fall of the complex lipid elaboration in the INH-resistant mycobacteria, may underline a role for these substances in the envelope of the mycobacterial cell that defends itself from the selecting attack of the antibiotic molecule and that keeps this phenotypic expression of INH-resistance in the mutants.