Phenotypic resistance in mycobacteria : is it because I am old or fat that I resist you?

Abstract

Synopsis Objectives We aimed to explore the phenomenon of phenotypic resistance to anti-mycobacterial antibiotics and to determine whether this was associated with cell age or presence of lipid bodies. Methods The accumulation of lipid body positive cells (lipid rich- LR) was followed using cell staining and flow cytometry. LR cells of M. smegmatis, M. marinum, M. fortuitum and BGC were separated from non-lipid body containing cells (lipid poor- LP) and their MBC determined. We also compared the MBC of LR and LP from “old” and “young” cultures. Results The LR cells of all species were more resistant to antibiotics than LP cells. For Mycobacterium bovis (BCG) the susceptibility ratios were as follows; Rifampicin-5X, isoniazid-16.7X, ethambutol-5X, ciprofloxacin-5X. Phenotypic resistance was found in LR cells irrespective of cell age. Conclusions We have shown that phenotypic antibiotic resistance is associated with the presence of lipid bodies irrespective of cell age. These data have important implications for our understanding of relapse in mycobacterial infections.